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A comprehensive review of European epidemiological studies on particulate matter exposure and health Prepared for CONCAWE’s Special Task Force on Health Effects of Air Pollution (H/STF-27) by:

E. Negri S. Gallus Department of Epidemiology, Mario Negri Institute, Milan, Italy

P. Boffetta International Agency for Research on Cancer, Lyon, France

J.K. McLaughlin International Epidemiology Institute, Rockville, MD, USA

C. La Vecchia Department of Epidemiology, Mario Negri Institute, Milan, Italy Institute of Medical Statistics and Biometry, University of Milan, Italy H/STF-27:

R. Taalman (Chairman) M. Banton J. Brown J.-P. Gennart D. King C. Money P. Roberts K. Rose E. Rushton G. Minsavage (Technical Coordinator) Reproduction permitted with due acknowledgement CONCAWE Brussels June 2011

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ABSTRACT

In 2006/2007 CONCAWE’s Health Management Group (through H/STF-27) commissioned a literature survey and review with the primary aim of summarising the current state of science on particulate matter in ambient air and its possible effects on health. The survey and review were undertaken by the Department of Epidemiology, Mario Negri Institute, Milan, Italy1, the International Agency for Research on Cancer, Lyon, France2, the International Epidemiology Institute, Rockville, MD, USA3 and the Institute of Medical Statistics and Biometry, University of Milan, Italy4. The authors of the study are Eva Negri1, Silvano Gallus1, Paolo Boffetta2, Joseph K. McLaughlin3 and Carlo La Vecchia1,4

The body of this report consists of a brief overview of the findings written by H/STF-27, followed by the detailed information in Appendix developed by the mentioned experts.

KEYWORDS

Air pollution, particulate matter, PM10, PM2.5, epidemiology, cardiovascular disease, cancer

INTERNET

This report is available as an Adobe pdf file on the CONCAWE website (www.concawe.org).

NOTE Considerable efforts have been made to assure the accuracy and reliability of the information contained in this publication. However, neither CONCAWE nor any company participating in CONCAWE can accept liability for any loss, damage or injury whatsoever resulting from the use of this information. This report does not necessarily represent the views of any company participating in CONCAWE.

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CONTENTS Page

SUMMARY IV 

1.  INTRODUCTION 1 

2.  EUROPEAN STUDIES ON SHORT-TERM PM EXPOSURE 2 

3.  EUROPEAN STUDIES ON LONG-TERM PM EXPOSURE 3 

4.  CONCLUSIONS 4 4.1.  RECOMMENDATIONS FOR FUTURE RESEARCH ON

HEALTH EFFECTS OF PM IN EUROPE 4 

5.  GLOSSARY 5 

6.  REFERENCES 8 

APPENDIX 1 DETAILED REPORT 9

EUROPEAN EPIDEMIOLOGICAL STUDIES ON PARTICULATE MATTER EXPOSURE AND HEALTH: A COMPREHENSIVE REVIEW OF THE LITERATURE 

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SUMMARY

There are a limited number of papers on the long term effect of air pollution on morbidity and mortality in Europe, particularly with reference to small particles with aerodynamic diameters less than 2.5 microns (PM2.5). Most information comes from US cohort studies, including the American Cancer Society Cancer Prevention Study II, the Harvard Six Cities Study, the Adventists’ Health Study of Smog, and the Veterans’ Cohort Mortality Study.

Ambient levels of several relevant pollutants are more variable within Europe than in the USA, and are in several areas comparably high. Selected European cohort studies, including the Netherlands Cohort Study on Diet and Cancer and the European Prospective Investigation on Cancer and Nutrition study found some association between indicators of air pollution such as PM10 or NO2 and lung cancer risk, but the results were inconsistent and inadequate to address the health effects of exposure to PM2.5.

In addition to the effect on mortality, there are open issues on the potential impact of air pollution on childhood asthma, allergy and airway disease. In consideration of the difficulties in estimating the prevalence of the conditions in various populations, these issues require additional focus.

In order to provide an indication on possible further analyses of existing European datasets, and on future new studies, a critical review of existing literature (with a focus on European data) was performed.

The project resulted in a detailed report (see Appendix 1) and in a paper published in the European Journal of Cancer Prevention [1].

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1. INTRODUCTION

A comprehensive review of European epidemiological studies published between 1996 and 2006 was conducted.

A search string was defined to select relevant scientific literature. The results of these searches were screened by two independent reviewers and only original studies conducted in Europe with some direct measure of ambient particulate matter (PM) exposure were selected for this review. Studies investigating the effect of long-term exposure on cardiovascular disease (CVD) were included. Cancer studies that provided proxies of PM exposure (e.g. distance of the residence from a major road) were also included. Approximately 150 studies met the inclusion criteria.

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2. EUROPEAN STUDIES ON SHORT-TERM PM EXPOSURE

The outcomes considered were mortality (total and by cause), hospital admissions for cardiovascular and respiratory diseases, and physician visits for respiratory diseases.

Several studies have investigated the association between day-to-day variations in PM concentrations and mortality or emergency hospital admissions. Many of these studies, however, had limitations, either because they were based on small populations or had problems in the statistical approach used, which in several instances tended to artefactually maximise the investigated association. Different and non-comparable measures of PM (PM with diameter <10 µm (PM10), Black Smoke (BS), Total Suspended Particulate (TSP) etc.) were used in various studies.

Most of the European studies found a direct association between mortality and various indicators of PM levels. The multicentric APHEA2 study provided the best estimate of the relation between PM and day-to-day mortality in Europe.

The interpretation of studies on CVD admissions and PM exposure is complicated by the use of different lag times and the combination of emergency and elective hospital admissions (as well as other variations in the definition of outcome) in some of the studies. Despite these limitations, the evidence from European studies supports the hypothesis of an association between air pollution and hospital admissions for CVD. The results on respiratory admissions provided some support for an association between daily variations in air pollution and hospitalization for respiratory disease, although the specificity of the association with PM was not clarified.

Information on the separate effects of coarse, fine and ultrafine PM is limited. Given that more and more areas within Europe have, in recent years, started measuring fine and/or ultrafine PM, it is likely that in the next few years studies will investigate the effects of coarse, fine and ultrafine PM separately. Investigations aimed at separating the effects of PM of different diameters will have to deal with the thorny statistical and interpretational problems of the analysis of highly correlated variables, a problem which has also arisen in the investigation of several correlated pollutants, e.g. PM, NO2, CO and SO2.

Very few results are available from Central and Eastern European countries.

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3. EUROPEAN STUDIES ON LONG-TERM PM EXPOSURE

Few European studies have investigated the long-term effects of PM exposure on health. Ecological studies are suggestive of a link and are generating hypotheses, but, given the potential biases inherent in their design, they cannot provide a solid base for inference.

Record linkage studies include a large number of cases, but the lack of individual variables, particularly smoking data, renders this type of study difficult to interpret.

Only a limited number of analytic studies have been conducted so far. Many of these were based on cohorts designed for other purposes but have exploited the availability of PM concentration data in the area under study. This has led to studies that were often based on small population size, often with exclusions of parts of the study population for which exposure data could not be retrieved or were not available.

In almost all long term studies conducted so far, the exposure to ambient PM has been estimated only on the base of the subjects’ home address. No additional information was available on characteristics of the home (e.g. floor of residence) or of the subject’s individual exposure pattern. Misclassification of exposure is likely to occur and to affect results.

Mortality was associated with various measures of long-term exposure to air pollution in cohort studies from the Netherlands, Germany and France, and in a record linkage study from Norway. The excesses were mainly attributed to cardiovascular and respiratory causes.

The evidence on long-term PM exposure and CVD morbidity is limited and difficult to interpret.

A few studies suggested associations between long-term PM exposure and asthma, lung function and various respiratory symptoms in children, although results were often not significant and not consistent. For adults, no clear evidence emerged for chronic bronchitis or asthma. Studies on air pollution and lung function, on the other hand, reported possible associations.

No clear indication of association emerged from the few studies investigating the relationship between long-term air pollution and lung or other cancers. Overall, the evidence is limited and inconsistent for this association. Limitations in the design of several studies conducted so far hinder any definite conclusion regarding cancer and long-term exposure to air pollution.

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4. CONCLUSIONS

4.1. RECOMMENDATIONS FOR FUTURE RESEARCH ON HEALTH EFFECTS OF PM IN EUROPE

Previous studies on short-term effects of PM in Europe allow a general quantification of the risks. However, information on the possible confounding or modifying effect of covariables, and, in particular, data on course, fine and ultrafine particles are limited. Still, with the exception of Central and Eastern Europe where few data are available, further research on short-term effects of air pollution should not be given high priority.

Only a limited number of analytic studies have been conducted in Europe on long-term effects of air pollution, and these were mainly cohorts designed for different purposes. Their ability to provide valid results was limited by sub-optimal strategies for exposure assessment leading to misclassification, low statistical power, and heterogeneity of approaches. While it is possible that additional exposure data can be retrieved for these and other existing longitudinal studies, it is uncertain whether this approach would lead to major advances in our knowledge of health effects. In any case, priority should be given to the co-ordination and harmonization of exposure data in existing cohorts.

The establishment of new ad hoc studies represents the preferred strategy to provide new insights on long-term effects of air pollution. In areas where estimation of long-term PM exposure could be reconstructed, a case-control design should be considered. The design and implementation of new cohort studies would provide, in the long-term, the most reliable information, but would require great effort in terms of time and resources. Such new studies would rely on uniform methods to measure air pollutants, and be based on an increased number of new measuring stations. Participants should be periodically re-contacted and, in addition to information on possible outcomes, new exposure information based on a uniform methodology should be collected. Such new cohorts should give priority to the inclusion of populations from Central and Eastern Europe, and in particular, areas where air pollution might be higher and adverse health effects may be detected sooner than in less polluted areas of Europe.

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5. GLOSSARY

ACS American Cancer Society

ACS-CPS II American Cancer Society – Cancer Prevention Study II

AHSMOG Adventists Health Study of Smog

AIC Akaike Information Criterion

AMI Acute Myocardial Infarction

APHEA Air Pollution and Heath: a European Approach

BMI Body Mass Index

BS Black Smoke

CI Confidence Interval

CO Carbon Oxide

COPD Chronic Obstructive Pulmonary Disease

CV Cardiovascular

CVD Cardiovascular Disease

ECRHS I European Community Respiratory Health Study I

EPA Environmental Protection Agency (US)

EPIC European Prospective Investigation on Cancer and Nutrition

FEF25-75 Forced Expiratory Flow between 25th and 75th percent of the FVC

FEV1 Forced Expiratory Volume in one second

FVC Forced Vital Capacity

GAM Generalized Additive Model

GLM Generalized Linear Model

HEAPSS Health Effects of Air Pollution among Susceptible Sub-population

HEI Health Effects Institute

HR Hazard Ratio

ICD International Classification of Diseases

IHD Ischemic Heart Disease

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IQR Inter-Quartile Range

Lag x xth day Lag

Lag x-y average x-y days Lag

LCL Lower Confidence Limit

MC Mass Concentration

MEF25-75 Midexpiratory flow between 25 and 75th percent of the FVC

MeSH Medical Subject Headings

NC Number Concentration

NMMAPS National Morbidity, Mortality and Air Pollution Study

NO Nitrogen oxide

NO2 Nitrogen dioxide

NO3 Nitrate

NOx Oxides of nitrogen

NS Not Significant

OLS Ordinary Least Squares

OR Odds Ratio

O3 Ozone

PAARC Pollution Atmosphérique et Affections Respiratoires

PM Particulate Matter

PM10 PM with diameter <10 µm

PMx PM less than x μm in aerodynamic diameter

PNC Particle Number Concentration

RH Relative humidity

RR Relative Risk

SAPALDIA Study on Air Pollution and Lung Diseases in Adults

SES Socioeconomic status

SO2 Sulphur dioxide

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SO4 Sulfate

TSP Total Suspended Particles

UCL Upper Confidence Limit

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6. REFERENCES

1. Gallus, S. et al (2008) European studies on long-term exposure to ambient particulate matter and lung cancer. European Journal of Cancer Prevention 17, 191-194

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APPENDIX 1 DETAILED REPORT

EUROPEAN EPIDEMIOLOGICAL STUDIES ON PARTICULATE MATTER EXPOSURE AND HEALTH: A COMPREHENSIVE REVIEW OF THE LITERATURE

Prepared by: Eva Negri1, Silvano Gallus1, Paolo Boffetta2, Joseph K. McLaughlin3, Carlo La Vecchia1,4

1 Department of Epidemiology, Mario Negri Institute, Milan, Italy 2 International Agency for Research on Cancer, Lyon, France 3 International Epidemiology Institute, Rockville, MD, USA 4 Institute of Medical Statistics and Biometry, University of Milan, Italy

This report was supported by an unrestricted grant of CONCAWE to the International Epidemiology Institute. The authors thank Dimitrios Trichopoulos, University of Athens and Harvard School of Public Health, for comments.

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CONTENTS Page

SUMMARY 13 

1.  INTRODUCTION 16 

2.  METHODS 17 2.1.  RETRIEVAL OF DATA 17 2.2.  PRESENTATION OF FINDINGS 18 2.3.  STUDIES CONSIDERED 19 2.4.  KEY ABBREVIATIONS AND OTHER TERMS 19 

3.  SHORT-TERM PARTICULATE MATTER (PM) EXPOSURE AND MORTALITY 21 3.1.  THE APHEA STUDIES 1 AND 2 21 3.2.  LOCATION OF THE STUDIES 22 3.3.  STUDY DESIGNS 22 3.4.  INDEX OF EXPOSURE TO PARTICULATE MATTER 22 3.5.  STATISTICAL MODELS USED 22 3.6.  LAG TIME 24 3.7.  CO-POLLUTANTS 26 3.8.  CONFOUNDING/MODIFICATION EFFECT OF OTHER

ENVIRONMENTAL VARIABLES 29 3.9.  CAUSE-SPECIFIC MORTALITY 29 3.10.  MORTALITY DISPLACEMENT AND MEDIUM-TERM

EFFECTS OF PM 30 3.11.  ULTRAFINE, FINE AND COARSE PM 32 3.12.  SEX DIFFERENCES 35 3.13.  AGE DIFFERENCES 36 3.14.  SOCIOECONOMIC DIFFERENCES 38 3.15.  STUDIES IN PATIENTS WITH SELECTED DISEASES (COPD) 39 3.16.  REGIONAL DIFFERENCES 39 3.17.  THRESHOLDS AND DOSE-RISK RELATION 40 3.18.  COMPARISON OF EUROPEAN WITH LEADING NORTH

AMERICAN STUDIES 42 3.19.  CONCLUSIONS 42 

4.  SHORT-TERM PM EXPOSURE AND CARDIOVASCULAR DISEASE (CVD) HOSPITAL ADMISSIONS 44 4.1.  THE APHEA2 STUDY 44 4.2.  THE HEAPSS STUDY 46 4.2.1.  Analysis on the general population 46 4.2.2.  Analysis on survivors of first AMI 50 4.3.  NATIONAL MULTICITY STUDIES 51 4.4.  STUDY DESIGN, STATISTICAL MODEL AND LAG TIME 52 4.5.  INDEX OF EXPOSURE TO PM, FINE, ULTRAFINE AND

COARSE PM AND CO-POLLUTANTS 52 4.6.  OUTCOME DEFINITION AND EFFECT FOR DIFFERENT

CAUSES OF HOSPITAL ADMISSION AND AGE GROUPS 53 4.7.  CONCLUSIONS 54 

5.  SHORT-TERM PM EXPOSURE AND RESPIRATORY HOSPITAL ADMISSIONS 55 5.1.  THE APHEA1 STUDY 55 5.2.  THE APHEA2 STUDY 57 5.3.  NATIONAL MULTICITY STUDIES 59 

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5.4.  FINE AND COARSE PM 59 5.5.  CONCLUSIONS 60 

6.  SHORT-TERM PM EXPOSURE AND OUTPATIENT VISITS 61 

7.  ANALYTIC STUDIES ON LONG-TERM PM EXPOSURE AND MORTALITY 62 7.1.  STUDY DESIGNS, SAMPLE SIZE, TIME FRAME AND

POPULATION DEFINITION 62 7.2.  ASSESSMENT OF EXPOSURE TO PM AND CO-

POLLUTANTS 62 7.3.  STATISTICAL MODEL AND CONTROL OF CONFOUNDING 63 7.4.  MAIN RESULTS 63 7.5.  EFFECT MODIFICATION BY AGE, SEX, SOCIOECONOMIC

STATUS OR OTHER VARIABLES 68 7.6.  COMPARISON OF EUROPEAN WITH LEADING NORTH

AMERICAN STUDIES 69 7.7.  CONCLUSIONS 70 

8.  ECOLOGIC STUDIES ON LONG-TERM PM EXPOSURE AND MORTALITY 71 

9.  LONG-TERM PM EXPOSURE AND CARDIOVASCULAR MORBIDITY 74 

10.  LONG-TERM PM EXPOSURE AND RESPIRATORY MORBIDITY OR SYMPTOMS 76 10.1.  LONG-TERM PM EXPOSURE AND ASTHMA IN CHILDREN 76 10.2.  LONG-TERM PM EXPOSURE AND LUNG FUNCTION IN

CHILDREN 76 10.3.  LONG-TERM PM EXPOSURE AND RESPIRATORY

SYMPTOMS IN CHILDREN 78 10.4.  LONG-TERM PM EXPOSURE AND RESPIRATORY

MORBIDITY OR SYMPTOMS IN ADULTS 81 10.5.  CONCLUSIONS 82 

11.  LONG-TERM PM EXPOSURE AND CANCER 83 11.1.  ANALYTIC STUDIES ON LUNG CANCER 83 11.2.  ECOLOGIC STUDIES ON LUNG AND OTHER CANCERS 86 11.3.  STUDIES ON AIR POLLUTION AND CANCER IN

CHILDREN 86 11.4.  COMPARISON OF EUROPEAN WITH LEADING NORTH

AMERICAN STUDIES 86 11.5.  CONCLUSIONS 87 

12.  DISCUSSION AND RECOMMENDATIONS FOR FUTURE STUDIES 88 12.1.  STUDIES ON SHORT-TERM EXPOSURE 88 12.2.  STUDIES ON LONG-TERM EXPOSURE 89 12.3.  RECOMMENDATIONS FOR FUTURE RESEARCH ON

HEALTH EFFECTS OF AIR POLLUTION IN EUROPE 90 

13.  REFERENCES 173 

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APPENDIX 1.1 SHORT-TERM PARTICULATE MATTER (PM) AND MORTALITY (DERIVED FROM EPA 1997) 186 

APPENDIX 1.2 SHORT-TERM PARTICULATE MATTER (PM) AND RESPIRATORY MORBIDITY 188 

APPENDIX 1.3 LONG-TERM PARTICULATE MATTER (PM) AND MORTALITY 189 

APPENDIX 1.4 LONG-TERM PARTICULATE MATTER (PM) AND RESPIRATORY MORBIDITY 190 

APPENDIX 1.5 LONG-TERM PARTICULATE MATTER (PM) AND LUNG CANCER 192 

APPENDIX 1.6 REFERENCES TO APPENDICES 193 

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SUMMARY

The US Environmental Protection Agency (EPA) reviewed data from studies on particulate air pollution (particulate matter, PM) and health published between 1996 and 2002 (US EPA, 2004). Herein, we have conducted a comprehensive review of the European epidemiological studies published between 1996 and 2006.

By means of Medline literature searches, we identified a number of studies, which were then screened by two independent reviewers for inclusion. We selected original studies conducted in Europe with some direct measure of ambient particulate matter (PM) exposure. For studies investigating the effect of long-term exposure on cardiovascular disease (CVD) and cancer, we included also studies providing proxies of PM exposure (e.g. distance of the residence from a major road). Approximately, 150 studies met the inclusion criteria. Studies published before 1996, and included in the EPA report are presented in an appendix, but are not commented on in the text.

1) Studies on short-term PM exposure

The outcomes considered were mortality (total and by cause), hospital admissions for cardiovascular and respiratory diseases, and physician visits for respiratory diseases.

Several studies have investigated the association between day-to-day variations in PM concentrations and mortality or emergency hospital admissions. Many of these studies, however, had limitations, either because they were based on small populations or had problems in the statistical approach used, which in several instances tended to artefactually maximise the investigated association. Different and non-comparable measures of PM (PM with diameter <10 µm (PM10), Black Smoke (BS), Total Suspended Particulate (TSP) etc.) were used in various studies.

Most of the European studies found a direct association between mortality and various indicators of PM levels. The multicentric APHEA2 study provided the best estimate of the relation between PM and day-to-day mortality in Europe. The APHEA2 study was based on a large population derived from several different areas in Europe, and the study data have been thoroughly re-analyzed to evaluate the influence of different statistical models, different time lags (up to 40 days), and the modification effects of some city characteristics, such as temperature or humidity, but also the percentage of people aged >65 years and of smokers. In the APHEA2 study, the estimated increase in total number of deaths associated with an increase of 50 µg/m3 of PM10 (lag 0-1 days) ranged from 2.1% to 3.3%, according to the statistical model used. For an increase in BS of 50 µg/m3 the estimated increase ranged from 1.4% to 2.8%. The associations of PM indicators with mortality approximately halved after adjustment for NO2. Medium-term (40 days) analyses showed that the observed effect is likely not due to mortality displacement, i.e., a mere anticipation of time of deaths of a few days. On the contrary, medium-term effect estimates tended to be two times higher than short-term ones, indicating a possible underestimation of the global effect of PM when only a few days are considered. This problem appeared more pronounced for respiratory than for CVD deaths.

The interpretation of studies on CVD admissions and PM exposure is complicated by the use of different lag times and the combination of emergency and elective hospital admissions (as well as other variations in the definition of outcome) in some of the studies. Despite these limitations, the evidence from European studies supports the hypothesis of an association between air pollution and hospital

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admissions for CVD. The results on respiratory admissions provided some support for an association between daily variations in air pollution and hospitalization for respiratory disease, although the specificity of the association with PM was not clarified.

Although age at death is, with sex, the only individual characteristic readily available from death certification data, the modifying effect of age on the relation between short-term PM exposure and mortality/morbidity has not been fully explored. The data from the APHEA2 study suggest that the effect of air pollution is greater at older ages.

Confounding by individual characteristics is not a major issue, since in time series comparisons are made from one day to another, using the same background populations. In the few studies that have analyzed data using a case-crossover design in addition to a time series approach, the results were comparable.

Limited or inadequate information is available in Europe on modification of the effects of air pollution exerted by individual variables (other than age and sex), e.g. socioeconomic status (SES), lifestyle habits (e.g. smoking), underlying medical conditions (e.g. COPD (chronic obstructive pulmonary disease), coronary disease, diabetes), occupational exposures, etc.

Information on the separate effects of coarse, fine and ultrafine PM is limited. Given that more and more areas within Europe have, in recent years, started measuring fine and/or ultrafine PM, it is likely that in the next several years studies will investigate the effects of coarse, fine and ultrafine PM separately. Investigations aimed at separating the effects of PM of different diameters will have to deal with the thorny statistical and interpretational problems of the analysis of highly correlated variables, a problem which has also arisen in the investigation of several correlated pollutants, e.g. PM, NO2, CO and SO2.

Presently, very few results are available from Central and Eastern European countries.

2) Studies on long-term exposure

Few European studies have investigated the long-term effects of PM exposure on health. Ecologic studies are suggestive and hypothesis generating, but, given the potential biases inherent in their design, they cannot provide a solid base for inference.

Record linkage studies include a large number of cases, but the lack of individual variables, particularly smoking data, renders this type of study difficult to interpret.

Only a limited number of analytic studies have been conducted so far. Many of these were based on cohorts designed for different purposes, which have exploited the availability of PM concentration data in the area under study. This has led to studies that were often based on small population size, often with exclusions of parts of the study population for which exposure data could not be retrieved or were not available.

In short-term time series, comparisons are ideally made between different days within individuals, and adjustment for day of week and holidays is often performed. In contrast, studies of long-term exposure are necessarily based on comparisons between individuals, and on cumulative exposure assessment. Misclassification of exposure is likely to occur and to affect results. In almost all studies conducted so

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far, the exposure to ambient PM has been estimated only on the basis of the home address of the subjects. No additional information was available on characteristics of the home (e.g. type of dwelling) or of the subject’s individual exposure pattern.

Mortality was associated with various measures of long-term exposure to air pollution in cohort studies from the Netherlands, Germany and France, and in a record linkage study from Norway. The excesses were mainly attributed to cardiovascular and respiratory causes.

The evidence on long-term PM exposure and CVD morbidity is scant and difficult to interpret.

A few studies suggested associations between long-term PM exposure and asthma, lung function and various respiratory symptoms in children, although results were often not significant and not consistent. For adults, no clear evidence emerged for chronic bronchitis or asthma. Studies on air pollution and lung function, on the other hand, reported positive results.

No clear indication of association emerged from the few studies investigating the relation between long-term air pollution and lung or other cancers. Overall, the evidence is scant and inconsistent for this association. Limitations in the design of several studies conducted so far hinder any definite conclusion regarding cancer and long-term exposure to air pollution.

3) Recommendations for future research on health effects of air pollution in Europe

Previous studies on short-term effects of air pollution in Europe allow a general quantification of the risks. However, information on the possible confounding or modifying effect of covariates, and mainly data on coarse, fine and ultrafine particles are limited. Still, with the exception of Central and Eastern Europe, where few data are available, further research on short-term effects of air pollution should not be given high priority.

Only a limited number of analytic studies have been conducted in Europe on long-term effects of air pollution, and these were mainly cohorts designed for different purposes. Their ability to provide valid results was limited by sub-optimal strategies for exposure assessment leading to misclassification, low statistical power, and heterogeneity of approaches. While it is possible that additional exposure data can be retrieved for these and other existing longitudinal studies, it is uncertain whether this approach would lead to major advances in knowledge of health effects. In any case, priority should be given to the co-ordination and harmonization of exposure data in existing cohorts.

The establishment of ad hoc studies represents the preferred strategy to provide new insights on long-term effects of air pollution. In areas where estimation of long-term PM exposure could be reconstructed, the case-control design should be considered. The design and implementation of new cohort studies would provide, in the long-term, the most reliable information, but would require great effort in terms of time and resources. Such new studies would rely on uniform methods to measure air pollutants, and be based on an increased number of new measuring stations. Participants should be periodically re-contacted and in addition to information on possible outcomes, new exposure information based on a uniform methodology should be collected. Such new cohorts should give priority to the inclusion of populations from Central and Eastern Europe, where air pollution is higher and adverse health effects may be detected sooner than in less polluted areas of Europe.

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1. INTRODUCTION

Although most epidemiological research on health effects of air pollution has focused on short-term exposure, a few studies have considered long-term exposure. The US Environmental Protection Agency (EPA) reviewed data of studies on particulate air pollution (particulate matter, PM) and health published between 1996 and 2002 (US EPA, 2004).

There is relatively little published on the long-term effect of air pollution on morbidity and mortality in Europe, particularly with reference to small aerodynamic particles with diameters less than 2.5 microns (PM2.5). Most information comes from US cohort studies, including the American Cancer Society - Cancer Prevention Study II (ACS-CPS II), the Harvard Six Cities Study, the Adventists Health Study of Smog (AHSMOG), and the Veterans’ Cohort Mortality Study.

Ambient levels of several relevant pollutants are more variable within Europe than in the USA, and are, in several areas, comparably high. Selected European cohort studies, including the Netherlands Cohort Study on Diet and Cancer and the European Prospective Investigation on Cancer and Nutrition (EPIC) study found some association between indicators of air pollution such as PM10 or NO2 and lung cancer risk, but the results were inconsistent and inadequate to address the health effects of exposure to PM2.5.

In addition to the effect on mortality, there are open issues on the potential impact of air pollution on childhood asthma, allergy and airway disease. In consideration of the difficulties in estimating the prevalence of these conditions in various populations, these issues require additional focus.

In order to provide indication on possible further analyses of existing European datasets, and on future new studies, we performed a critical review of existing literature (with focus on European data). This leads to recommendations on the design of future epidemiological studies on health effects of air pollution in Europe.

We have therefore updated the literature from Europe up to 2006, and conducted a comprehensive review of the European epidemiological studies published between 1996 and 2006.

Most of the original studies considered the association between short-term exposure to ambient pollutants (including PM) and morbidity/mortality. Several components and measures of air pollution were analysed with reference to incidence or mortality from cardiovascular disease (CVD), hospital admissions for respiratory disease, incidence of asthma and other respiratory conditions, and decreased pulmonary function. However, the results were not consistent across studies, and precise quantification of risks remains unattainable.

Only a few studies provided data on long-term exposure to PM and morbidity/mortality in adults.

The main results of these studies are summarised in the present report.

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2. METHODS

2.1. RETRIEVAL OF DATA

We retrieved from PubMed the abstracts of all the journal articles on European epidemiologic studies (96 papers) included in the EPA report. We identified the Medical Subject Headings (MeSH) terms common to all the 96 papers, and defined a search string to select the scientific literature for the period 2002-2006 as follows:

("air pollutants" [MeSH] OR "air pollution" [MeSH]) AND humans [MeSH] AND ("cardiovascular diseases" [MeSH] OR neoplasms [MeSH] OR "respiratory tract diseases" [MeSH] OR hospitalization [MeSH]).

Using PubMed, on November 1, 2006 we retrieved 3,168 papers, which were then included in an electronic database using Endnote (version 9).

On the basis of title, abstract (when available), and keywords (MeSH terms), two independent reviewers (Eva Negri and Silvano Gallus) independently classified all the 3,168 papers, in order to identify studies of high interest using a 1-5 score:

1. Paper not pertinent or of limited interest (eliminate) 2. Probably not pertinent or of limited interest (eliminate if the other reviewer

also scores 1 or 2) 3. Not possible to evaluate on the basis of title/abstract/keywords only 4. Of high interest (important review or methodologic papers or original studies

out of Europe) 5. Original study from Europe

From the first selection, 2,383 papers were eliminated (both reviewers’ score <3).

Among the other 785 papers, approximately 100 papers were scored 5 by both reviewers. To these 785 papers we added 532 papers not yet “indexed for MEDLINE” (“in process”, therefore without MeSH terms), using on November 25, 2006, the following search string:

(air [tiab] OR pollut* [tiab] OR "particulate matter" [tiab] OR ambient [tiab]) AND (particulate* [tiab] OR PM [tiab] OR PM10 [tiab] OR PM2.5 [tiab] OR PM5 [tiab]) NOT(medline[sb]).

On the basis of title, abstract (when available), and keywords (MeSH terms), Eva Negri and Silvano Gallus performed a second independent double classification of the 1,317 papers using a score from 1 to 10:

1. Paper of limited interest (eliminate) 2. Methodologic study of limited interest 3. Original study not conducted in Europe of limited interest 4. Review of limited interest 5. Not possible to evaluate on the basis of title/abstract/keywords, only 6. Original study not conducted in Europe of high interest 7. Methodologic study of high interest 8. Review of high interest 9. Original European study on co-pollutants only 10. Original European study on PM.

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From the second selection we eliminated (both reviewers’ score <5 OR (one reviewer’s score=5 AND the other’s <5) 738 papers. Among the other 579 papers, 144 were considered original European studies by both reviewers. Most of these studies evaluated the association with short-term exposure to ambient pollutants including PM.

Other searches targeting cancer were performed, using a specific search string on PubMed. Furthermore, all the publications from the most important international studies (e.g., APHEA and HEAPSS) were searched. Finally, reference lists of a number of published papers (original articles and reviews) were examined.

For all the 579 papers remaining in the database, the PDF of the original article was retrieved. All papers scored 9 or 10 by at least one reviewer were examined and classified according to outcome.

2.2. PRESENTATION OF FINDINGS

We used the tables on short-term PM exposure of the EPA 2004 report as basis (US EPA, 2004), and updated them with the new studies not included in the EPA 2004 report. From the original EPA tables we have abstracted only studies conducted in Europe. In the tables, the studies already present in the EPA 2004 report are shown on a grey background, while the new studies have a white background. The EPA 2004 report did not include tables summarizing findings from studies on long-term PM exposure and mortality, and CVD and cancer morbidity. We summarized papers published from 1996 also for these outcomes in a similar way.

The EPA 2004 report also included the re-analyses of some studies published in a HEI report (HEI, 2003). This report originated from the fact that problems were found in the statistical software S-Plus routine used in many studies to fit generalized additive models (GAM): the default convergence criteria used in the S-Plus GAM function resulted in biased estimates and under some circumstances the standard errors of the estimates were underestimated (Dominici et al, 2002). The authors were invited to reanalyze their data using more stringent convergence criteria. The corrected analyses were published in the HEI report and compared with the original ones. Fully parametric models (GLM with natural or penalized splines) were also explored as alternative ways of estimation in the re-analyses in the HEI report.

We have modified the order in which the studies appeared in the EPA tables, since we have grouped them in the following categories: 1) Large international multicity studies 2) Nationwide studies 3) Sub-national studies, grouped by country and geographic area (Northern, Central, Southern, Eastern Europe) 4) Studies on selected populations.

In the Appendix we reported the description of European epidemiologic studies published before 1996, and cited in the EPA 1997 report (US EPA, 1997)

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2.3. STUDIES CONSIDERED

For the present revision of the literature we considered the following studies:

I. Studies on short-term PM exposure and mortality, including all the studies providing estimates for PM.

II. Studies on short-term PM exposure and CVD hospital admission including all the studies providing estimates for PM.

III. Studies on short-term PM exposure and respiratory hospital admission including all the studies providing estimates for PM.

IV. Studies on short-term PM exposure and respiratory medical visits including all the studies providing estimates for PM.

V. Studies on long-term PM exposure and mortality, including all the studies providing estimates for PM.

VI. Ecologic studies on long-term PM exposure and mortality, including all the studies providing estimates for PM.

VII. Studies on long-term PM exposure and CVD morbidity, including all the studies providing estimates for PM, or proxies of PM, as those studies having as outcome the distance between a major road and the residence.

VIII. Studies on long-term PM exposure and respiratory morbidity or symptoms, including all the studies providing estimates for PM.

IX. Studies on long-term PM exposure and cancer, including all the studies providing estimates for PM, other co-pollutants or proxies of PM, as those studies having as outcome the distance between a major road and the residence.

We have not considered studies on short-term PM exposure and pulmonary function tests or other symptoms in asthmatics or non-asthmatics.

2.4. KEY ABBREVIATIONS AND OTHER TERMS

AIC Akaike Information Criterion AMI Acute Myocardial Infarction APHEA Air Pollution and Heath: a European Approach BMI Body Mass Index BS Black Smoke CI Confidence Interval CO Carbon Oxide COPD Chronic Obstructive Pulmonary Disease CVD Cardiovascular Disease EPA Environmental Protection Agency (US) FEF25-75 Forced Expiratory Flow between 25th and 75th percent of the FVC FEV1 Forced Expiratory Volume in one second FVC Forced Vital Capacity GAM Generalized Additive Model GLM Generalized Linear Model HR Hazard Ratio ICD International Classification of Diseases IQR Inter-Quartile Range

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IHD Ischemic Heart Disease Lag x xth day Lag Lag x-y average x-y days Lag LCL Lower Confidence Limit MEF25-75 Midexpiratory flow between 25 and 75th percent of the FVC NO Nitrogen oxide NO2 Nitrogen dioxide NOx Oxides of nitrogen NS Not Significant OLS Ordinary Least Squares OR Odds Ratio O3 Ozone RH Relative humidity PM Particulate Matter PMx PM less than x μm in aerodynamic diameter PNC Particle Number Concentration RR Relative Risk SO2 Sulphur dioxide TSP Total Suspended Particles UCL Upper Confidence Limit

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3. SHORT-TERM PARTICULATE MATTER (PM) EXPOSURE AND MORTALITY

Table I (modified and updated from EPA 2004 Table 8A-1) presents the studies conducted in Europe that have considered the association between short term exposure to PM and mortality. The APHEA studies I and II were the only large international multicity studies on short-term effects of PM on mortality in Europe. For this reason, a brief description of the APHEA studies is given below, and particular prominence is given to the results of the APHEA2 study throughout this chapter.

3.1. THE APHEA STUDIES 1 AND 2

The APHEA1 study ended before the EPA 2004 report, and its main results were included there (Katsouyanni et al, 1997; Samoli et al, 2001; Samoli et al, 2003).

The APHEA1 study was conducted in 12 European cities over the period 1975-1992. However, BS indicators were available for 8 cities and PM10 for 6 cities only. In a first publication there was a significant heterogeneity between European areas, with a positive association between BS and PM10, and total mortality in western European cities and no effect in central/eastern European ones (Katsouyanni et al, 1997). Two subsequent re-analyses of the data using different statistical models (GAM models with smoothing terms for seasonal trends and weather) considerably reduced heterogeneity between the two areas (Samoli et al, 2001; Samoli et al, 2003). In those re-analyses, BS and PM10 were positively associated to mortality overall and in the two areas separately, although the size of the effect depended on the statistical model used, and particularly on the method used to adjust for meteorological variables and other confounders.

Several publications concerning the APHEA2 study were already included in the EPA 2004 report (Touloumi et al, 1997; Katsouyanni et al, 2001; Katsouyanni et al, 2003; Zanobetti and Schwartz, 2003), and new publications have appeared thereafter (Aga et al, 2003; Zanobetti et al, 2003; Touloumi et al, 2005; Analitis et al, 2006). Moreover, we have added to Table I the data concerning a publication (Zanobetti et al, 2002) that should have been included in the EPA 2004 report, but was not listed there. In fact, in Table 8A-1 of the EPA 2004 report, the article by Zanobetti and Schwartz 2003, which was one of the re-analyses conducted within the HEI project, was indicated as “reanalysis of the above study”, but that study (Zanobetti et al, 2002) was missing from the table.

The APHEA2 study used data over the period 1990-1997 (most cities had data for at least 5 years) and included 29 European cities for a total population of over 43 million.

Data on BS were available for 14 cities, and PM10 data for 21 cities.

The estimated effects of BS and PM10 on total non accidental mortality, reanalyzed using more stringent convergence criteria, were presented in the HEI report (Katsouyanni et al, 2003). The APHEA2 study found a direct association between mortality and the average level of PM10 on the same day and on the day before. The total mortality excess risk per 50 µg/m3 of PM10 varied between 2.1% (95% CI 1.2-3.0) and 3.3% (95% CI 2.7-3.9), according to the statistical model considered.

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The new analyses of the APHEA2 study not included in the EPA 2004 report have concerned the comparison of short and medium-term effects of exposure to PM10 on mortality (Zanobetti et al, 2003), the effects of BS and PM10 exposure on cardiovascular and respiratory mortality (Analitis et al, 2006), the effect of PM on mortality in the elderly (Aga et al, 2003) and the effect of different modeling techniques of influenza epidemics on the association between PM10 and total and cardiovascular mortality (Touloumi et al, 2005).

3.2. LOCATION OF THE STUDIES

Besides the APHEA studies, which were based on several cities located throughout Europe, there were one nationwide study, conducted in the Netherlands (Hoek et al, 2000; Hoek et al, 2001; Hoek, 2003, Fisher, 2003 #726) and a number of studies conducted in one or more cities/areas, from the UK, Ireland, Finland, the Netherlands, Germany, the Czech Republic, France, Italy and Spain.

3.3. STUDY DESIGNS

Almost all studies were time series correlating daily mortality with particulate levels on one or more days. Only a study in the general population and a study in patients with COPD adopted a crossover design.

3.4. INDEX OF EXPOSURE TO PARTICULATE MATTER

Several different PM measures were used, including Total Suspended Particulate (TSP), Black Smoke (BS), PM10, PM7, PM13, PM15, PM2.5, PM2.5-10, Number Concentration (NC) and Mass Concentration (MC) of ultrafine (0.01-0.1 µm) and fine (0.1-2.5 µm) PM. A few studies also estimated associations with SO4

2- and NO3-.

In the APHEA1 study the indicators of PM exposure used were BS, available for 8 cities, and PM10, estimated for 6 cities and computed as follows: 0.55*TSP (3 cities), PM13 (2 cities) and PM7 (1 city).

In the APHEA2 study data on BS were available for 14 cities, and PM10 was estimated for 21 cities as follows: measured directly as PM10 (11 cities), by regression to BS (2 cities) or TSP (2 cities), or as % of TSP (6 cities).

3.5. STATISTICAL MODELS USED

Different statistical models for time series analyses were used in various studies. The GAM has been the favored method in recent years. The HEI report (HEI, 2003) provides a comprehensive assessment of the impact of different statistic approaches, and in particular several ways of adjusting for time-related factors, such as long term trends in pollution levels and mortality.

The APHEA2 study has been analyzed using different statistical approaches, and was re-analyzed in the HEI report (Katsouyanni et al, 2003). Shortly, overall estimates were obtained using a two stage model. In the first stage an estimate of the association between either PM10 or BS was obtained for each city using the same statistical model. In the second stage city-specific effect estimates were regressed on city-specific covariates to obtain an overall estimate and to explore confounding, using both fixed and random effects models. The single city models

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were adjusted for seasonality, long-term trends, temperature, humidity, influenza, day of the week, holidays and unusual events if necessary. The lag was set a priori to the average of days 0 and 1.

The results of the effects on daily total number of deaths of PM10 are reproduced below (Table 1 from Katsouyanni et al, 2003). As compared to the original estimates, based on the default convergence criteria, the use of more strict convergence criteria did not materially modify the estimated betas (-4%). The use of a parametric approach by means of natural splines led to increased standard errors and a 30-40% reduction in the estimated betas, and to a 10-15% reduction when penalized splines were used. Although the size of the effect was reduced using alternative statistical methods, this reanalysis confirmed the findings of the original investigation (Katsouyanni et al, 2001), i.e. that there is a positive association between daily number of deaths and PM10 levels.

Significant heterogeneity between cities was found for all models considered.

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3.6. LAG TIME

The definition of the lag time, i.e. the time interval between exposure (as determined by ambient levels of particulate) and outcome, remains still a controversial issue.

On one hand, there is the need to investigate which is the “correct” time to be used in the model. Moreover, the interval between exposure and effect may differ according to cause of death considered, reflecting different mechanisms of action. Rossi and colleagues (Rossi et al, 1999) in their analysis of the effects of ambient TSP levels on mortality in Milan, Italy, focused on the difference in lag times on cause-specific mortality. They reported a significant association on the concurrent day for deaths from respiratory infection and from heart-failure, while an association with myocardial infarction and COPD were found for the means of 3 to 4 days prior to death. In the APHEA2 study, the extension of the lag time from 2 to 6 days led to an increase of 20-30% of the estimated effect for CVD deaths, while the increase was more marked (75-90%) for respiratory deaths (Analitis et al, 2006).

On the other hand, many investigators tried a number of different single day and cumulative day lag times, and chose to present the results with the strongest association. The authors generally did not apply statistical methods (e.g. to alter statistical significance levels according to the number of tests performed) to allow for the multiple testing. This is, from a statistical point of view, questionable.

The APHEA1 study was also affected by this problem, since the “best” individual day models (days 0, 1, 2, 3) and the “best” average of 2-4 consecutive days was selected for each centre (Katsouyanni et al, 1997). The lag time used was also allowed to vary across centres.

Conversely, in the APHEA2 study the lag time was set a priori to the average of days 0 and 1 (except for analyses on medium term and harvesting effects). Thus the results of the APHEA2 study are unaffected by the problem of multiple comparison due to the use of several different lag times.

A few studies presented a table showing how the estimated beta varies according to the chosen lag time.

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For example, Figure 2 from Bremner (Bremner et al, 1999) above shows the estimated effects on total mortality of individual day lags 0, 1, 2 and 3 of cumulative lags mean 0-1, 0-2, and 0-3 for PM10 and BS (and gaseous pollutants). In this case, the estimated effects are all positive albeit non significant, although the point estimates varied. In other cases, however, the direction of the effect and the statistical significance vary according to the chosen lag (Ponka et al, 1998).

For the reasons explained above, we prioritize studies in which the lag time has been set a priori over those in which several lag times have been considered.

Most of the studies reported the association between daily deaths and pollution concentration on the same day or 1-2 days before. However, a few European studies investigated the medium-term effects of air pollution levels considering lag times up to 40 days (Zanobetti et al, 2002). The findings of these studies are reported in section 10 of the present chapter.

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3.7. CO-POLLUTANTS

Many studies measured other pollutants besides PM. The ones reported in most studies were SO2, NO2, O3 and CO. However, relatively few studies investigated the confounding effect of other pollutants on the relation between PM and mortality.

The APHEA1 study collected data on levels of SO2, but they did not introduce SO2 in the model because it was too strongly correlated to BS and PM10.

The APHEA2 study measured SO2, O3 and NO2, besides BS and PM10, and presented two-pollutant models in Table 2 of the paper by Katsouyanni et al, 2001 (see below).

For both PM10 and BS, adjustment for O3 resulted in an increase in the estimated coefficients, particularly for BS (+9% for PM10 and +40% for BS), adjustment for SO2 resulted in a slight decrease of the association (-13% for PM10 and -18% for BS), while the association with mortality halved after adjustment for NO2 (-49% for PM10 and -49% for BS). In all two-pollutant models, however, the associations between PM10 and BS with total mortality remained statistically significant.

Katsouyanni and colleagues (Katsouyanni et al, 2001) also fitted multivariate second stage regression models with the estimated effect parameters of PM and NO2 for each city as dependent variables and average long-term NO2 concentrations as a potential effect modifier. That analysis showed that, after adjustment for confounding of the daily fluctuations of NO2 on the PM effect parameters, NO2 continued to act as an effect modifier: the estimated increase in total daily mortality for an increase of 10 µg/m3 of PM10 was 0.19% in a city with low average NO2 concentration, and 0.80% in a city with high average NO2 concentration. Corresponding estimates for BS were 0.26% and 0.73%. Also the ratio of PM10 to NO2 was an effect modifier.

These estimates were affected by the problems due to the use of incorrect convergence criteria pointed out by Dominici and colleagues (Dominici et al, 2002). In the reanalysis presented in the HEI report (Katsouyanni et al, 2003), corresponding results were not shown. The authors however stated that exploration of the pattern of effect modification using parametric methods (natural and penalized splines) preserved exactly the same pattern of effect modification as the original analysis.

Hoek and colleagues (Hoek et al, 2000; Hoek, 2003), in their nationwide study in the Netherlands also extensively investigated the confounding effect of several

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co-pollutants (O3, SO2, NO2, CO) on the relation between total mortality and PM10 and BS levels. They also measured fine particle component sulfate (SO4

2-) and nitrate (NO3

-).

The Table 2 of the paper by Hoek (Hoek, 2003) below reproduces part of the results from the reanalysis in HEI report. We will comment on the results for the “GAM strict” model. For natural splines results were similar.

In the one pollutant models (lag 0-6 days) all pollutants considered were significantly and positively associated with mortality, with the exception of SO4

2- for which the positive association was not significant. The point estimates were 1.023 for an increase of 100 µg/m3 PM10, 1.026 for 50 µg/m3 of BS, 1.022 for 25 µg/m3 of SO4

2-, and 1.030 for 50 µg/m3 of NO3

-.

Table 5 from Hoek (Hoek, 2003) (see below) presents results for two pollutant models.

The RR for all 4 indicators of particulate increased after adjustment for O3 or CO. Conversely, after adjusting for SO2 or NO2, the RR for PM10 was below 1, and that of BS was more than halved (1.012) and no longer statistically significant. Adjustment for SO2 or NO2 did not substantially change the estimated effects of SO4

2- (1.019 and 1.022, respectively) and NO3- (1.027 and 1.029), although the

standard error of the parameters increased with the introduction of the other pollutant.

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It is also important to notice that the effect of SO2 and NO2 tended to remain positively and significantly associated with total mortality after adjustment for PM indicators.

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In conclusion, these data suggest that PM10 is not the only pollutant of concern, and the PM10-effect should be carefully adjusted for co-pollutant effects.

3.8. CONFOUNDING/MODIFICATION EFFECT OF OTHER ENVIRONMENTAL VARIABLES

In most studies the authors adopted various methods to adjust for seasonality and long-term trends in air pollutants and daily mortality, while investigating the day to day association. Most studies also adjusted for meteorological variables like temperature at various lags and humidity. Other confounders often considered were day of the week, holydays and influenza epidemics.

One study conducted a sensitivity analysis examining the effect of different methods of modeling influenza epidemics on the estimated association between BS and total mortality in Barcelona, Spain (Tobias and Campbell, 1999). It found that the coefficient for BS decreased and became not statistically significant, when influenza was modeled by the daily number of cases, instead that by dummy variables identifying epidemic periods. Conversely, a reanalysis of the APHEA2 data controlling for influenzas by ten different methods found that the significant and positive association between PM10 and daily number of deaths remained and even increased after controlling for influenza, regardless of the method used for control (Touloumi et al, 2005).

In the APHEA2 study, the effect of PM was larger in warmer and drier cities, although temperature was a more important effect modifier than humidity (Katsouyanni et al, 2001). The HEI reanalysis (Katsouyanni et al, 2003) confirmed the same pattern of effect modification. When the authors investigated cause-specific mortality, average annual temperature and humidity were effect modifiers for CV death, but not for respiratory causes (Analitis et al, 2006)

In the Netherlands study, the effects of PM were stronger in summer than in winter (Hoek et al, 2000; Hoek, 2003). A stronger association in warmer periods was also reported in a few other studies (Anderson et al, 1996; Michelozzi et al, 1998; Anderson et al, 2001).

3.9. CAUSE-SPECIFIC MORTALITY

In the majority of studies, the endpoint considered was total non accidental mortality (ICD9 codes 1-799). A number of studies also considered CVD (ICD9 codes 390-459) and respiratory non cancer mortality (ICD9 codes 460-519) separately. In general, CVD deaths account for roughly half of total non accidental deaths, and often results for total and CVD mortality are similar. Conversely, respiratory mortality accounts for a much smaller proportion of total mortality. Thus, the results for respiratory mortality are much more affected by random variation, particularly in smaller studies.

Analitis and colleagues (Analitis et al, 2006) analyzed the effects of BS and PM10 separately for CVD and respiratory mortality in the APHEA2 study.

In Table 1 of their paper (below), they summarized the main results.

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The results for the two causes were, in proportional terms, remarkably similar. For example, under the random effect model, the estimated % increase in daily number of deaths for an increase of 10 µg/m3 of PM10 was 0.76% (0.47, 1.05) for CVD causes and 0.71% (0.22, 1.20) for respiratory causes. Corresponding values for BS were 0.62% and 0.84%. Estimates under the fixed effect model were lower, but still statistically significant for both causes of death. Their analysis suggested that the major impact of PM on CVD mortality occurs in the first two days (lags 0, 1), while the effects on respiratory mortality persist for several days.

Several other smaller studies considered CVD and respiratory mortality separately, but results were not always easy to interpret, given the smaller numbers of deaths, and hence the greater random variation in cause-specific mortality analyses. In the study based on 9 French cities (5 of which had data on BS) the excess RR (lag 0-1) associated with an increase of 50 µg/m3 was 2.9% (1.3, 4.4) for total, 3.1% (0.5, 5.5) for CVD and 2.7% (-2.6, 8.3) for respiratory mortality (Le Tertre et al, 2002b).

In the Netherlands study, Hoek and colleagues (Hoek et al, 2001) analyzed associations with specific CVD causes of death. They found that deaths due to heart failure (ICD9 428), arrhythmia (ICD9 427), cerebrovascular causes (ICD9 430-436) and thrombocytic causes (ICD9 415.1, 433-4, 444, 452-3) were more strongly associated with PM (as well as with gaseous pollutants) than other CVD causes of death, including ischaemic heart diseases. This was confirmed in the HEI reanalysis (Hoek, 2003).

Cause-specific mortality was also considered in a study from Milan, Italy (Rossi et al, 1999). The authors found that respiratory infections and heart failure deaths were best predicted by TSP on the concurrent day, while, for deaths from myocardial infarction and COPD, lag 3-4 was the best predictor. The estimated RRs, however, were similar for heart failure (7% for 100 µg/m3 TSP) and myocardial infarction (10%).

3.10. MORTALITY DISPLACEMENT AND MEDIUM-TERM EFFECTS OF PM

Although several time series found a direct relation between levels of PM and mortality, it has been questioned whether these excess deaths occur in those who would have died in a few days anyway (harvesting effect). If this is true, one would

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expect an increase in mortality in the few days following a day with high levels of PM, followed by a decrease in the medium term. Zanobetti and colleagues (Zanobetti et al, 2002) analyzed the issue using the APHEA2 data. Due to time and resource constraints, it was decided a priori to limit the analysis of mortality displacement to the ten largest cities from different countries. Using the usual two stage methodology of the APHEA studies, different lag modes were fitted to the data. First a model for lag 0-1 was fitted, in order to estimate short-term effects. Then, different models for lag 0-40, measuring the cumulative PM10 exposure of the onset day and the previous 40 days, were fitted: an unconstrained distributed lag model, where one parameter for each day was used, and polynomial distributed lags of the third and fourth degree.

Estimated PM10 effect per 10 µg/m3 are given below, for the original analysis (Zanobetti et al, 2002) and for the HEI reanalysis (Zanobetti and Schwartz, 2003) using more strict convergence criteria and penalized splines.

Beta (SE)

Lag, model Original GAM Strict GAM Penalized Splines

0-1 0.70 (0.14) 0.67 (0.14) 0.57 (0.15)

0-40, unconstrained 1.61 (0.39) Not given Not given

0-40, cubic 1.57 (0.67) Not given Not given

0,40 4th degree 1.61 (0.30) 1.45 (0.30) 1.08 (0.40)

Since the estimated effect of PM on mortality more than doubles when lag 0-40 days is used, instead of lag 0-1, the authors concluded that i) the effects observed in daily time series are not due primarily to short-term mortality displacement, and ii) the short-term risk assessment based on lag 0-1 associations likely underestimates the PM effect on mortality. The HEI reanalysis did confirm the same results, although all estimates were reduced for penalized splines. Similar results were reported in studies conducted in Milan, Italy (Zanobetti et al, 2000) and Dublin, Ireland (Goodman et al, 2004).

Zanobetti and colleagues (Zanobetti et al, 2000) also examined mortality displacement separately for cardiovascular and respiratory disease. In Table 2 of their paper (below), they found that the effect size more than doubled for CVD deaths, and increased 5-fold for respiratory deaths, when they used lag 0-40 instead than lag 0-1.

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They also found a different pattern of mortality risk over time for CVD and respiratory deaths, with the elevation in risk of death after exposure declining more slowly over time for respiratory rather than CVD mortality.

3.11. ULTRAFINE, FINE AND COARSE PM

Only a few studies specifically considered fine or coarse PM separately.

Anderson and colleagues (Anderson et al, 2001) considered the association between PM10, BS, PM2.5, PM2.5-10 and SO4

2- on daily mortality in a study conducted between 1994-1996 in the west Midland conurbation of the UK. To compare estimates, they used as measurement unit for each pollutant the difference between the 10th and the 90th percentiles. The relative risk estimates at lag 0-1 were not significant for any of the PM indicators considered in the all season analysis (see Table 3 of their article below).

The authors noted, however, that all measures of PM except PM2.5-10 showed significant positive effects in the warm season (figure 1 below).

Although not significant, the estimates for coarse PM were not substantially different from those of other PM indicators, particularly for the warm season. Moreover, the correlation between PM10 and PM2.5 was 0.92, thus the effects of the two measures were difficult to distinguish.

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A study from Erfurt, Germany, conducted between 1995 and 1997 assessed the association and role of particles of different size with respect to mortality in an urban setting (Wichmann et al, 2000). One specific aim was to compare the role of ultrafine (aerodynamic diameter <0.1 µm) and fine (0.1-2.5 µm) PM on mortality.

Number concentration (NC) was measured for each particle size range, while mass concentration (MC) was calculated for each particle size range from the NC assuming sphericity of particles and constant density.

In Table 18 of their report (see below) the authors show the estimated effect for the best fitting single day model and for polynomial distributed lag models over 5 or 6 days.

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The authors concluded that fine and ultrafine particles had direct effects on mortality which were comparable in strength, and the effect was stronger if the contributions of all size classes were added up, mainly for respiratory diseases, followed by CVD diseases. When they considered two-pollutant models, they concluded that “the

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observed correlations of gaseous pollutants and mortality were explained by colinearity of the gases to particles rather than by an independent causal effect”.

The authors also stated that there were indications from their data that the effects of fine particles occur more immediately (lag 0-1) and the effects of ultrafine particles more delayed (lag 4-5). The HEI Review Committee agreed with the authors’ conclusion that fine and ultrafine particles were associated with mortality, but did not agree with the authors’ suggestion of a different lag effect (immediate vs delayed) for the two particle size. The Committee also did not agree with the authors’ interpretation that the association of SO2 with mortality was an artifact due to confounding by PM.

The Committee also pointed out that the study had strengths like the use of a more precise PM metric, but also had concerns regarding the statistical analysis and interpretation, mainly linked to the problems of multiple comparisons, the sensitivity of the overall estimates to confounders like influenza, and to the definition of lag.

The HEI reanalysis using more strict convergence criteria for GAM and fully parametric methods (GLM) confirmed the major interpretations and conclusions of the original study (Stölzel et al, 2003).

An extension of the study to the period 1995-2001 currently published online ahead of print (Stolzel et al, 2006), found associations between ultrafine particles NC and total (RR=1.029, 95% CI 1.003, 1.055 for an increase of 9748 cm-3) and cardio-respiratory (RR=1.031, 95% CI 1.003, 1.060) mortality. No association between fine particle MC and mortality was found.

Particle number concentration (PNC) - as a proxy for ultrafine particles - was also considered in a case-crossover study conducted between 1998 and 2000 in Rome on out-of-hospital coronary deaths (Forastiere et al, 2005). The study found a direct association between out-of-hospital fatalities and PNC, PM10 and CO. However, PNC were measured for the period April 2001-Jun 2002 and estimated retrospectively for the study period by means of a regression model with PNC as the dependent variable and other pollutants (PM10, CO, NO2 and O3) and meteorological readings as explanatory variables. Moreover, given that the correlation between measured and estimated PNC was 0.90, and that between CO and PNC was 0.89, estimated PNCs were not a better proxy of “true” PNC than CO. Nevertheless, the same study was re-analyzed as a time series and yielded similar results (Stafoggia et al, 2005).

A study from the coal basin of the Czech Republic (Peters et al, 2000) found a significant association between PM10 and mortality only at lag 1 (RR=1.098, 95% CI 1.07, 1.197 for 100 µg/m3 increase). For each given lag, estimates for a 100 µg/m3 increase of PM2.5 were lower than for a corresponding increase in PM10 (RR=1.059, 95% CI 0.980, 1.144 at lag 1).

3.12. SEX DIFFERENCES

Only a few studies considered sex differences in the association between PM and mortality. Although one study from Northern Bohemia, Czech Republic (Kotesovec et al, 2000), found different results in men and women (significant associations only for men below age 65 years, and for women only above age 65 years) these differences may be due to random variation in subgroup analysis. Another study

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from Rome found similar associations between PM10 and fatal out-of-hospital coronary events for the two sexes (Forastiere et al, 2005).

3.13. AGE DIFFERENCES

In the APHEA2 study, the proportion of elderly in various cities was an effect modifier of the relation between PM10 and mortality, and the mortality excess risk for a 10 µg/m3 increase in PM10 was 0.54% (0.38, 0.69) in a city at the 25th percentile of the distribution of proportion of elderly, and 0.76% (0.63, 0.90) in a city at the 75th percentile (Katsouyanni et al, 2001). Corresponding estimates for BS were 0.48% (0.34, 0.62) and 0.70% (0.51, 0.90).

When the analyses were carried out separately for CVD and respiratory mortality, the modifying effect was stronger for respiratory mortality (Analitis et al, 2006). For BS, the proportion of elderly explained less than 10% of the heterogeneity between cities for CVD mortality, while for respiratory mortality the effect at the 25th percentile was 0.44% (-0.01, 0.88) and at the 75th percentile was 1.57% (0.99, 2.16).

When analysis of the APHEA2 data was limited to the population aged 65 years or more (Aga et al, 2003) larger effects of PM10 and BS were found than in the all age analysis (see Table 1 from their article below).

The increases in estimates when analysis was restricted to the elderly population were around 10% for PM10 and around 20% for BS.

In the analysis restricted to the elderly, the same pattern of effect modification as in the overall analysis was reported, with larger PM effects in cities with higher NO2 levels, higher temperature, lower humidity, higher age-standardized annual mortality rate, higher proportion of individuals ≥65 years and from Northwestern and Southern Europe.

An issue that still remains unclear is the quantification of the effect of PM on mortality in the population younger than 65 years. In the cities included in the

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APHEA2 study the proportion of deaths occurring in the elderly ranged between 67% and 88% (Aga et al, 2003). Since the majority of deaths occurred in the elderly, mortality at all ages and in the elderly are highly correlated. Restricting mortality at younger ages may result in substantially different PM effect estimates, which however are clearly affected by larger random variation.

The APHEA2 analysis of the medium-term effects of PM (Zanobetti et al, 2003) found no association between PM10 and total mortality at age 15-64 years, but significant associations at ages 65-74 years and ≥75 years.

The association between PM10 and BS levels on the one hand and daily mortality on the other by age group was considered also in the Netherlands study (Fischer et al, 2003). Separate estimates were provided for the age groups <45, 45-64, 65-74 and ≥75 years for total mortality and for deaths due to CVD, COPD and pneumonia (see below figure 1 of Fisher et al., 2003). The RRs were calculated for a difference between the 1st and 99th percentiles (i.e., 80 µg/m3 for PM10 and 40 µg/m3 for BS).

From Fig 1 of Fischer et al., 2003. The successive age groups are <45, 45-64, 65-74 and ≥75 years.

When they analyzed specific causes of deaths, the pattern for CVD deaths was similar to overall mortality. Large random variation affected the estimates for COPD and pneumonia. However, for pneumonia, estimates appeared higher below age 65 years for PM10, where the estimates in subsequent age categories were 1.43, 1.71*, 1.24 and 1.12* (the asterisk indicated that the CI does not include 1). No clear pattern across age groups for pneumonia mortality emerged for BS (RRs=0.74, 1.26, 0.95 and 1.12*, respectively).

The few smaller studies investigating the effect in different age groups were affected by substantial random variation, and yielded conflicting results: some found indications that the effect of PM was larger or limited to elderly people (Michelozzi et al, 1998; Goodman et al, 2004; Forastiere et al, 2005) some to younger people (Ponka et al, 1998; Bremner et al, 1999; Wichmann et al, 2000) and some did not find noticeable differences between age groups (Hoek et al, 1997; Prescott et al, 1998).

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3.14. SOCIOECONOMIC DIFFERENCES

One case-crossover study investigated the effect of PM10 on daily mortality by socioeconomic status (SES) among residents in Rome aged over 35 years between 1998 and 2001 (Forastiere et al, 2005). For each death from natural causes, the day on which the death occurred was the “case” day, and the same days of the week within the same month were chosen as control days. Hospital discharge data for the 2 years before deaths were used to estimate history of selected diseases requiring hospitalization, including diabetes, hypertension, heart failure and COPD. As a surrogate for individual SES, two area-based indicators were used, i.e. the median per capita income and the average SES index of the census block of residence (Rome is divided in 5,736 census blocks, with an average of 480 inhabitants). The SES index was based on several characteristics of the census block, like educational level, occupational category, unemployment rate, family size, crowding and proportion of rented/owned dwellings. The two SES indexes were than divided in four groups by the 20th, 50th and 80th percentiles.

In the population of Rome the percentage of people living in areas with high levels of PM10, CO, NOx and benzene increased with increasing SES indicator, particularly for SES index: 9% of those with low SES, and 12%, 21% and 40% in those with mid-low, mid-high and high SES, respectively. This was due to the fact that people with high SES tended to live nearer to the more polluted city centre.

There was a monotonous inverse relation between both SES indicators and hospitalization rates for many chronic conditions - including malignant neoplasms, several cerebrovascular diseases, COPD and diabetes - two years to 29 days before deaths.

Figure 2 of the article presents the estimated % increase in daily mortality by SES:

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The effects of ambient PM10 on mortality were similar for the first three SES categories, but there was no association in the high SES category.

The authors concluded that the effect of PM was stronger in lower social classes. Given the observed pattern of exposure and of history of hospitalization for several severe conditions, they argued that the different effect of PM in SES groups was likely due to the differential burden of chronic health conditions conferring a greater susceptibility to lower SES groups.

However, as the authors pointed out, the monotonous increase in comorbidity across SES strata is not mirrored by a corresponding increase in PM effect, which appears, if anything, dichotomic.

3.15. STUDIES IN PATIENTS WITH SELECTED DISEASES (COPD)

Three articles (Garcia-Aymerich et al, 2000; Sunyer et al, 2000; Sunyer and Basagana, 2001) investigated the relation between ambient PM and mortality in a cohort of patients with COPD from Barcelona, Spain.

All patients aged 35 years or more attending the emergency room services in Barcelona for COPD between 1985 and 1989 were recruited (9,987 people).

In a time series analysis on the 3,245 patients who died in the period 1985-1889 (Garcia-Aymerich et al, 2000) the estimated percent increase in total mortality associated with an increase of 20 µg/m3 in the patients in the cohort was 2.3% (-0.8, 15) and was, if anything, lower that the one estimated in the general population (5.6%, 95% CI 2.7, 8.7). Given the higher mortality rates in patients with COPD, in absolute terms, the effect may be higher than in the general population.

A case-crossover study (Sunyer et al, 2000) was conducted in patients from the cohort who died in the period 1990-1995 (2,305 patients). PM levels on the day of death were compared to those one week before and one week after. The estimated percent increase in mortality for an increase in BS of 20 µg/m3 was 11.2% (1.7, 21.5) for all causes of deaths, 7.7% (1.3, 26.4) for CV mortality, and 18.2% (2.5, 36.5) for respiratory deaths.

When the same design was used to estimate PM10 effects (Sunyer and Basagana, 2001), the percent increase in total mortality for a 27 µg/m3 (IQR) increase was 11.4% (0, 24). Although adjustment for other pollutants (NO2, O3, CO) resulted in larger SE of the parameters, the point estimates were not substantially modified and ranged from 10% to 13%.

However, it is important to notice that subjects with COPD are less likely to be exposed to outdoor air levels of pollutants because they spend more time indoors.

3.16. REGIONAL DIFFERENCES

Regional differences were investigated within the APHEA Project in eight western and five central-eastern European countries, using different statistical models (Samoli et al, 2001). Using sinusoidal terms for seasonal control and polynomial terms for meterologic variables, the effects of air pollution on daily mortality were lower in central-eastern European cities (Katsouyanni et al, 1996; Katsouyanni et al, 1997). Data were re-analysed using generalized additive models (GAM), in order to

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smooth differences in risk estimates across various countries. Thus, when excluding days with pollutant levels above 150 µg/m3, an increase in BS by 50 ug/m3 was associated with a 3.1% (2.6, 3.6) increase in mortality overall, a 3.1% (2.3, 3.9) increase in western countries, and a 2.9% (1.8, 4.1) increase in central-eastern countries (Samoli et al, 2001).

The APHEA2 study, including 29 European cities, has provided the best framework to investigate regional variation of PM effect in Europe. The median levels of PM10 concentration among the 21 cities providing data ranged between 14 to 166 ug/m3. For BS median concentrations ranged between 9 and 64 ug/m3 among the 14 cities providing data. The estimated increase in mortality for an increase of 10 µg/m3 ranged from -0.6% to 1.5%, and there was significant heterogeneity between the single city estimates. Several city-specific factors acted as effect modifiers of the relation between PM10 and mortality, the effects being greater in cities with high average NO2 levels, high mean temperature and low standardized mortality. Most of the heterogeneity between cities was explained by the inclusion of these three factors in the model (Katsouyanni et al, 2001).

3.17. THRESHOLDS AND DOSE-RISK RELATION

Combining estimates for cities included in the APHEA2 study and of a few other studies, Anderson and colleagues investigated the relation between mean PM10 concentration level and estimated short-term effect on total mortality (Ross Anderson et al, 2004) [Ross Anderson et al., 2004]. In Figure 1 of the report (shown below), the estimated PM10 effect on all-causes mortality is plotted against annual average levels of PM10 in individual European areas. No apparent relationship was evident, indicating that the relative risk does not depend on the average levels of PM10, at least for a certain range of concentration.

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As Brunekreef and Holgate pointed out, current knowledge, in particular from European studies, on short-term exposure to air pollution and mortality does not allow to understand whether thresholds concentrations exist below which air pollution has no effect on population health. In fact, most of the European studies analysing the association between air pollution levels and risk for health analyse time-series data. In these studies, total excess risks are usually estimated according to an increment of various measures of PM. This way of presentation of findings does not take into account the absolute pollution levels. In fact, in case of non-linearity, an increase from 100 to 110 µg/m3 does not have the same population impact as an increase from 10 to 20 µg/m3. This also demonstrates that time-series methodology is not suitable for detection of thresholds. (Brunekreef and Holgate, 2002).

In most studies, the statistical analysis took care of allowing a substantial variation in the possible shape of the confounders. For the PM effects however, generally linear, or in some cases log-linear, relationship with the dependent variable was assumed in the analysis. In the APHEA2 study, days with over 150 µg/m3 were excluded because the investigators deemed that a linear relation may not hold at higher doses. In their analysis of the National Morbidity, Mortality and Air Pollution Study (NMMAPS), Dominici and colleagues found that the national average exposure-response curve was linear, although some modest departures from the linear model were observed in some regions (Dominici et al, 2003).

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3.18. COMPARISON OF EUROPEAN WITH LEADING NORTH AMERICAN STUDIES

The two largest multicity studies from Europe (APHEA2) and the United States (National Morbidity Mortality Air Pollution Study, NMMAPS) have been reanalyzed using similar methodology within the HEI project (HEI, 2003).

The table below illustrates the estimated increase in total mortality from nonexternal causes in the two studies under different statistical models.

Estimated percent mortality change for an increase in daily PM10 of 10 µg/m3 in Europe and the United States

Model NMMAPS (lag 1) APHEA2 (lag 0-1)

GAM estimated with default S-Plus parameters

0.4 (0.3-0.6) 0.6 (0.4-0.8)

GAM with more stringent criteria for convergence

0.3 (0.2-0.8) 0.6 (0.4-0.8)

GLM with natural cubic splines 0.2 (0.1-0.3) 0.4 (0.2-0.6)

As can be seen, in both studies the estimated excess mortality changes according to the model used. In Europe, estimates tend however to be higher than in the Unites States. Some differences in the estimation process may explain, at least in part the differences obtained, including the different lag times used and the confounders included in the model). Differences in the quality of the air pollution measurements or in the pattern of exposure of the underlying population may also contribute to the discrepancies in results. Katsouyanni and colleagues (Katsouyanni et al, 2003), however, suggested that a possible explanation may be the difference in relative sources and contribution of PM10 in Europe and in the US. In particular diesel cars are rare in the US, while in many European cities they approach 50% of cars.

Since the APHEA2 study found that other city-specific characteristics acted as effect modifiers on the PM-mortality relation, it is also possible that differences in these factors between Europe and the US explain the different strength of the observed relation.

3.19. CONCLUSIONS

In spite of the many studies conducted in Europe, several uncertainties on the relation between ambient PM levels remain, even because of some still unresolved methodological issues.

Most of the European studies (Table I) found a direct association between mortality and various indicators of PM levels.

In the largest, multicity study (APHEA2) the estimated increase in total number of deaths associated with an increase of 50 µg/m3 of PM10 (lag 0-1) ranged between 2.1% and 3.3% according to the statistical model used (Katsouyanni et al, 2003).

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In the Netherlands study (Hoek, 2003), the corresponding estimates ranged between 0.9% and 1.2% according to statistical model and lag time (1 or 0-6) considered. For both studies, the 95% confidence intervals did not include unity.

For an increase in BS of 50 µg/m3 the APHEA2 study’s estimates ranged between 1.4% and 2.8% and in the Netherlands study’s between 1.9% and 2.6%.

Medium-term (40 days) analyses have shown that the observed effect is likely not due to mortality displacement, i.e., a mere anticipation of time of deaths of a few days. On the contrary, medium-term effect estimates tended to be two times higher than short-term one, indicating a possible underestimation of the global effect of PM when only few days are considered. This problem may be more pronounced for respiratory deaths than for CVD ones.

Given the marked correlations between PM and gaseous pollutants, the reciprocal confounding effect is an important issue in the light of a causal interpretation of the observed association. Introduction of highly correlated variables in statistical regression models creates problems of instability and can seriously affect the estimates.

This may explain, at least in part, the inconsistencies observed between the major studies. In the APHEA2 study the effect of PM was only slightly reduced after adjustment for SO2, but almost halved, remaining statistically significant, after adjustment for NO2. In the Netherlands study, no association with PM10 was shown after adjustment for SO2 or NO2.

Besides the issue of confounding, other pollutants can also act as effect modifier on the relation between PM and mortality, as suggested by the APHEA2 study. This relation can be further modified by other meteorological variables, like temperature and humidity.

Individual variables - like age, general health status and SES - can also affect this relation.

Finally, the European studies aiming at separating the effects of fine (and ultrafine) and coarse PM are still too few and small-scaled to allow clear conclusions.

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4. SHORT-TERM PM EXPOSURE AND CARDIOVASCULAR DISEASE (CVD) HOSPITAL ADMISSIONS

Table II (modified and updated from EPA 2004 Table 8B-1) presents European studies investigating the association between short-term ambient PM exposure and CVD hospital admissions. These include two international multicity studies, the APHEA2 (Le Tertre et al, 2002a) and the HEAPSS (von Klot et al, 2005; Lanki et al, 2006), two national multicity studies from France (Eilstein et al, 2004) and Italy (Biggeri et al, 2005) and a number of smaller studies from various countries.

4.1. THE APHEA2 STUDY

The APHEA2 study has been already discussed in the chapter on short term effects of PM on mortality. The analysis on CVD hospital admissions (Le Tertre et al, 2002a) was based on 8 cities/areas, i.e. Barcelona in Spain, Birmingham and London in the UK, Milan and Rome in Italy, Paris in France, Stockholm in Sweden and the whole of the Netherlands, for a total population close to 38 million.

The study period started between 1989 and 1994 and ended between 1994 and 1997, depending on the area. The number of days contributing to the analysis varied between city and PM exposure indicator, ranging between 930 and 2,904. Ambient PM exposure indicators used were BS, available for 5 cities, and PM10, measured directly in 5 cities, as PM13 in Paris and as 0.75*TSP in Milan and Rome. Days with levels of PM exposure indicators above 150 µg/m3 were excluded, because of the possible lack of linearity at higher doses.

Autoregressive Poisson models, adjusting for long-term trends, season, influenza and meteorology were used to estimate PM effects for each city. Pooled estimates were then obtained combining the city-specific effect estimates by means of fixed and random effect models. The lag was set a priori at 0-1.

Emergency admissions were used in all cities except Milan, Paris and Rome, where only general admission data were available. In order to exclude elective admissions, some diagnostic codes were excluded, based on the distinction between emergency and elective admissions in London for the period 1992-94. Causes with more than 70% of elective admissions were excluded, plus the code 414 (“other forms of ischemic heart disease”), for which 65% of admissions were elective. The outcomes considered were all cardiac causes (ICD9 390-429), ischemic heart disease (ICD9 410-413) and stroke (ICD9 430-438).

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Table 5 of the article (above) gives the pooled results for a 10 µg/m3 increase in PM10 or BS.

The percent increase of cardiac admissions for a 10 µg/m3 increase was 0.5% (0.3, 0.7) for PM10 and 0.8% (0.5, 1.2) for BS under the fixed effect model, and the estimates were higher when the analysis was limited to individuals above age 65 years. For IHD the estimates were 0.3% (-0.1, 0.6) below 65 years of age and 0.6% (0.3, 0.8) above age 65 years for PM10; and 0.1% (-0.4, 0.5) below 65 years and 1.1% (0.7, 1.5) above age 65 years for BS. No effect of PM10 or BS was evident for stroke admissions. Estimates from random effect models were either similar or moderately higher.

The authors also fitted two pollutant-models (see Tables 6 and 7 of the article below):

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Although in the titles of Tables 6 and 7 the term “total daily number of deaths” appears, the results likely refer to hospital admissions, as written in the text (mortality data were not presented in this paper). The effects of PM10 on cardiac, cardiac over 65 years, and IHD over 65 years admissions decreased after adjustment for CO, and disappeared after adjustment for NO2 or BS. Adjustment for NO2 about halved the effects of BS, which became non significant. In contrast, the point estimates of the BS effects on cardiac emergency admissions became bigger after adjustment for CO or PM10.

According to the authors, the stronger confounding of PM10 effect by NO2 – a secondary pollutant mainly influenced by diesel and non-catalyzed gasoline fuelled engines – than by CO – a primary traffic pollutant representing mainly gasoline fuelled engines – suggests that diesel exhaust was primarily responsible. The authors also suggested that this conclusion was supported by the fact that BS, which is dominated by diesel particles, was little affected by confounding from CO or PM10. This may be debatable, as BS may also reflect the contribution of other non traffic-related sources (coal, industrial, etc.).

4.2. THE HEAPSS STUDY

The Health Effects of Air Pollution among Susceptible Sub-population (HEAPSS) originally investigated the effect of traffic related air pollution on cardiac hospital readmissions in a cohort of subjects from five European cities who were admitted for first AMI (von Klot et al, 2005). In a subsequent analysis the group also investigated the association between air pollutants and hospitalization for first AMI, i.e., the event responsible for the inclusion into the HEAPSS cohort (Lanki et al, 2006). Thus, this second study is based on the general population, and not on a selected cohort.

4.2.1. Analysis on the general population

The HEAPSS study included five European cities, Augsburg in Germany, Barcelona in Spain, Helsinki in Finland, Rome in Italy and Stockholm in Sweden. For each city, the study period was within the range 1992 and 2000, and included at least three years.

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PM was measured as PM10 and PNC. In Augsburg, PM10 was estimated as 0.83*TSP, and in Barcelona data were missing for two years and were estimated by linear prediction from TSP and BS. Monitoring of PNC started in 1999 in Augsburg, and in April 2001 in the other cities. Thus, during the study period no direct measurement of PNC was available. City-specific models for estimating PNC from other pollutants and meteorological variables were developed for the period when PNC was measured, and applied then retrospectively to predict daily PNC concentrations during the study period (Paatero et al, 2005). The correlation of measured and predicted half of PNC, using split-halves technique ranged between 0.72 and 0.89 in the five cities, and that of day-to-day differences in measured and predicted PNC between 0.61 and 0.88 (Paatero et al, 2005). Levels of NO2, CO and O3 were also recorded and analyzed.

The data on hospitalizations for first AMI were collected using AMI registers in Augsburg and Barcelona, and hospital discharge registers in the other three cities. The ager range was over 35 in all cities. Augsburg included patients up to 74 years, and Barcelona up to 79 years. In order to increase specificity of AMI diagnoses, hospitalizations shorter than 3 days were excluded. Elective hospitalizations were also excluded in Helsinki and Stockholm. To select first AMI only, the recorded patient history was used in AMI registers, and a record linkage with the hospital discharge data of the previous three years was used in the other three cities. The presence of codes indicating a previous infarction (ICD9 412) as secondary diagnosis was also a reason for exclusion.

City-specific models were fitted in the first stage. Poisson regression, adjusting for non-linear effects by means of penalized splines in GAM was used for the analysis. Time trend, apparent temperature, barometric pressure, day of the week, holiday, and population reduction in summer were considered as confounders. Lags 0, 1, 2 and 3 were considered and presented in the article. The estimates were then combined by means of either fixed or random effect models in case of heterogeneity between city-specific estimates.

Table 4 of the paper (below) shows the relative risk of hospitalization for a first AMI for a 10 µg/m3 increase in PM10 and for a 10,000 particles/cm3 in PNC.

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PM10 was not associated with hospitalization for first AMI in all five cities, nor when the analysis was limited to the three cities using hospital discharge data to define the outcome. PNC was not associated in the overall analysis, but there was a 1.3% (0.0, 2.6) increase in hospitalization for first AMI at lag 0, albeit not at other lags, when the analysis was restricted to hospital discharge register data.

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The authors excluded Augsburg and Barcelona since the upper limit on age in the inclusion criteria reduced the power in these two cities, and this could be the reason for the lack of association. However, including more cities should have, if anything, increased the power of the study. Consequently, even if nominally based on five cities, the main conclusions are based on analyses on three cities only. Figure 1 of the paper on the left gives the city specific associations. Although the authors claimed that there was no heterogeneity between the three cities (Helsinki, Rome, and Stockholm) at lag 0, there appeared to be an heterogeneity between Rome and Stockholm, since the point estimate of each of these cities was not included in the 95% CI of the estimate of the other. In fact, Rome and Stockholm are the only two

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cities where some significant associations were observed. For Rome, a positive one at lag 0, and a strong inverse one at lag 3. For Stockholm, an inverse one at lag 1 and a positive one at lag 3.

The analysis was then conducted separately for fatal and non fatal AMI and for patients aged below and above 75 years, only for the three cities using hospital discharge data, and the results were presented in Table 5 of the article (see below).

No appreciable association emerged in this subgroup analysis for PM10. Significant associations emerged for fatal AMI below age 75, and for non fatal AMI above age 75 years. Effects were more pronounced during the warm season. Two pollutant models were not performed.

Given the pattern of association with PNC (and CO), the authors concluded that their study supports the hypothesis that exposure to traffic related air pollution increases the risk of AMI, and that the most consistent associations were observed among fatal cases aged <75 years and in the warm season.

4.2.2. Analysis on survivors of first AMI

An article by von Klot and colleagues presented the results of the HEAPSS study for hospital readmission for cardiac causes after a first AMI (von Klot et al, 2005). The cohort of subjects on which this analysis was based included all subjects who had had a first non fatal AMI during the study period, i.e., all the subjects who had had an outcome in the analysis presented above (Lanki et al, 2006) and did not die within 28 days from the event. The enrollment period coincided with the one of the previous analysis, and the follow-up period was extended up to 2000-2001 for all centres. The cohort consisted of 22,006 subjects. Endpoints were defined as hospital readmission within the study area for 1) AMI, 2) angina pectoris and 3) cardiac causes, i.e., a combined endpoint including the previous two, heart failure and dysrhythmia. The start of the follow-up was the 29th day after the index event,

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and the end of follow-up was either the endpoint of interest, death, migration out of study area, loss to follow-up or end of study period.

The levels of PM10 and PNC were defined as in Lanki et al (Lanki et al, 2006).

GAMs with penalized splines to control for confounders were used in city-specific models. The outcome was daily number of readmissions and the natural logarithm of the number of persons at risk each day was included as an offset. Pooled estimates were obtained by fixed or random effect models. Lag 0 was used for presenting results.

Table 3 of the article (below) presents the main results of their study.

PNC and PM10 were significantly associated with readmissions for cardiac causes. Point estimates for AMI only were higher than for cardiac causes, but not significant, because of smaller numbers of events resulting in wider CIs. Estimates for angina pectoris were above unity, but lower than for cardiac causes, and not significant.

In two-pollutant models, effects of PNC, CO and NO2 were not affected by PM10 or O3, while the association with PM10 was only slightly attenuated by traffic related pollutants.

4.3. NATIONAL MULTICITY STUDIES

Two multicity studies from France (Eilstein et al, 2004) and Italy (Biggeri et al, 2005) investigated the association between PM and hospital admissions for CVD.

The French study comprised nine cities, but the analysis on BS and CVD admissions was based on 5 cities, and that on PM10 and CVD admissions on 4. No significant associations were found for BS and PM10 at lags 0-1 and 0-5.

The Italian study was based on 8 cities. For two cities, PM10 was measured directly, while for the other six PM10 was estimated as a fraction of TSP. The pooled estimate of the percent change in number of admissions for cardiac causes (ICD9 390-429) for a 10 µg/m3 increase in PM10 (lag 0-1) was 0.77% (0.40, 1.15) under the fixed

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effect model and 0.82% (0.32, 1.32) under the random effect model. Results were similar to the random effect model when several Bayesian models were fitted.

4.4. STUDY DESIGN, STATISTICAL MODEL AND LAG TIME

As for mortality, almost all the studies were time series.

It is likely that some of the early studies (including the APHEA2 study) were affected by the statistical problems connected with the use of S-plus routines. However, in the case of mortality studies, the HEI reanalysis had shown that results changed only slightly by the use of more strict convergence criteria. Greater changes were observed by the use of different statistical models for the control of continuous confounders (HEI, 2003).

Some studies were also affected by multiple comparison problems due to the use of different lag times. The APHEA2 study defined lag time a priori while the HEAPSS study showed results for different lag times, and combined data across cities using the same lag time for each city. No evaluation of medium-term effects of PM on CVD hospital admissions was available.

4.5. INDEX OF EXPOSURE TO PM, FINE, ULTRAFINE AND COARSE PM AND CO-POLLUTANTS

The PM indexes used in the APHEA2 study were BS and PM10, and PM10 and PNC in the HEAPSS study. In both studies, PM10 was not measured directly in all cities, but was estimated either from PM13 or TSP.

Within the APHEA2 study, the RR estimates for both PM10 and BS are given for an increase of 10 µg/m3. The IQR however, was generally higher for PM10 (range 8.7-23.6 µg/m3) than for BS (range 7.3-17.5 µg/m3). However, when BS and PM10 were included together in a model, the effect of PM10 disappeared, while the effect of BS increased for cardiac causes overall, and was only slightly decreased for IHD.

In the HEAPSS study, no clear effect of PM10 was evident, except for certain subgroups. A problem in evaluating the results for PNC is the fact that PNC was estimated from regression on TSP or PM10 and other co-pollutants, rather than estimated directly. It is not clear how this may have affected the results. Overall, when all five cities were included, no clear effect emerged, while PNC was directly and significantly associated with AMI admissions when the analysis was restricted to the 3 cities that used hospital admission registers to ascertain the outcome, excluding the two cities where AMI registers were used. However, as previously pointed out, the results for PNC are not entirely convincing, given the exclusions a posteriori.

The conclusion of the HEAPSS study that AMI admissions are mostly related to traffic related air pollution are supported by a case-crossover study on non fatal AMI from Augsburg, Germany (Peters et al, 2004), that did not measure PM exposure, but found that transient exposure to traffic appeared to increase the risk of AMI.

In another article, the data from Rome included in the HEAPSS study were analyzed with a case-crossover design, confirming that in Rome PNC was associated with AMI risk at lag 0 (D'Ippoliti et al, 2003).

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One study from the West Midlands conurbation of the UK (Anderson et al, 2001) examined the association between fine (PM2.5) and coarse (PM2.5-10) PM on CVD emergency admissions separately. For the cardiovascular causes considered - i.e. all cardiovascular (ICD9 390-459), cardiac (ICD9 390-429), IHD (ICD9 410-414) at age 65+ years and stroke (ICD9 430-438) at age 65+ years – no consistent associations emerged with either BS, PM10, PM2.5 or PM2.5-10 (see Table 4 from the article, below).

The only significant finding was a strong negative association between PM2.5-10 (and SO2) and daily admissions for stroke at age 65+ years.

A small study from Trondheim, Norway, found no association between PM2.5 and cardiovascular admissions (Mannsaker et al, 2004).

As concerns adjustment for other co-pollutants, the APHEA2 presented result for two–pollutant models, while the HEAPSS briefly discussed them in the discussion.

4.6. OUTCOME DEFINITION AND EFFECT FOR DIFFERENT CAUSES OF HOSPITAL ADMISSION AND AGE GROUPS

The main problem in the definition of outcomes was the difficulty to distinguish, in some studies, between emergency and elective admissions. In the APHEA2 study, emergency admissions were not available for three cities (Milan, Paris and Rome). The authors tried to exclude admission diagnosis where a high proportion (over 65-70%) were elective, based on data from London. It is difficult to estimate how this

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may have affected the estimates. However, from the graphs presenting city-specific results, no difference was evident between these three cities and the others.

Within the range of CVD morbidity, different outcomes were considered in the various studies. The APHEA2 found associations with cardiac (ICD9 390-429) deaths overall, stronger over 65 years of age, and for IHD (ICD 410-413) over age 65 years. No clear association emerged for IHD below age 65 years, and for stroke over 65 years.

The outcome considered in the HEAPSS study was AMI (ICD 410). This outcome is overlapping with the IHD outcome considered in the APHEA2 study. To estimate comparability, in Italy in 1999 there were 89,079 hospital admissions for AMI, and 147,927 for the codes 411-413 [source Website of the Italian Ministry of Health, http://www.ministerosalute.it/programmazione/sdo/ric_informazioni/]. In contrast to the APHEA2 study, the HEAPSS study found the strongest associations for fatal AMI below age 65 years. This result should be interpreted with caution because apparent associations from subgroup analyses may arise by chance alone, given the multiple comparisons performed and the greater random variation due to the reduced sample size. Moreover, in the HEAPSS study the association with PNC in the older age group appeared, if anything, stronger for non-fatal events. These subgroup results are based on three cities only, since the other two cities were excluded because they had data on younger subjects only (even though those were the ones among whom the strongest relation was found in the other three cities).

The two multicity studies were based on partially overlapping populations, since three cities (Barcelona, Rome and Stockholm) were included in both projects.

As for mortality studies, there was some evidence from several studies that the effect of air pollution may be stronger in warmer or drier seasons/areas.

Finally, the HEAPSS study also analyzed the effects of PM on a susceptible population, i.e. survivors from a first AMI, and found stronger associations in this group than in the general population.

4.7. CONCLUSIONS

In the multicentric APHEA2 study, a significant increase in cardiac admission was reported for PM exposure, which might have resulted, in part, from confounding by NO2, a marker of traffic pollution. Similar results were reached in the general-population analysis of hospitalization for myocardial infarction in the HEAPSS multicentric study. Results in survivors of a first myocardial infarction were stronger than those in the general population. A multicentric study from Italy found an association with PM exposure, while a similar French study reported no association.

The interpretation of studies on cardiac admissions and PM exposure is complicated by the use of different lag times and the combination of emergency and elective hospital admissions (as well as other aspects of the definition of outcome) in some of the studies. Despite these limitations, the evidence from European studies supports the hypothesis of an association between air pollution and hospital admissions for cardiovascular diseases.

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5. SHORT-TERM PM EXPOSURE AND RESPIRATORY HOSPITAL ADMISSIONS

Table III (modified and updated from EPA 2004 Table 8B-2) presents European studies investigating the association between short-term ambient PM exposure and respiratory hospital admissions. These include two international multicity studies, the APHEA1 (Sunyer et al, 1997) and APHEA2 (Atkinson et al, 2001), two national multicity studies from France (Eilstein et al, 2004) and Italy (Biggeri et al, 2005), and a number of small studies from various countries. The two national multicity studies are the same already briefly discussed in the chapter on CV hospital admissions, since both outcomes were presented in the same article.

5.1. THE APHEA1 STUDY

An outline of the APHEA1 project has been already given in the chapter on mortality. One article investigated emergency admissions for asthma in Barcelona, Helsinki, London and Paris, i.e. the four cities participating to the APHEA project that collected data on asthma (Sunyer et al, 1997). Barcelona collected data on asthma emergency room visits in the age group 15-64 years, while London and Helsinki on daily asthma emergency admissions in children (0-14 years) and adults (15-64 years), and Paris on total asthma admissions in both age groups. Data for BS were not available for Helsinki. Thus, the analysis in children was limited to two cities (London and Paris), to which Barcelona was added for adults. The same two stage procedure (in the first stage an estimate of the association between either PM10 or BS was obtained for each city using the same statistical model; in the second stage city-specific effect estimates were regressed on city-specific covariates to obtain an overall estimate and to explore confounding, using both fixed and random effects models) was used as for the mortality analysis. Similarly, several one day and cumulative lags were fitted, and the best fitting one day and cumulative model was chosen for each centre. The study period was from 1986-87 to 1989-91, depending on city.

Table 2 of the paper (below) gives city specific and combined results for the age group 15-64 years.

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The pooled percent daily increase for a 50 µg/m3 increase in BS was 2.1% (-1.5, 5.9) for single day lags, and 3.0% (-1.9, 8.1) for cumulative lags. Single day lags used were 3 for Barcelona, and 0 for London and Paris. Cumulative lags combined were 0-3 for Barcelona and Paris, and 0-1 for London.

Table 3 of the paper (below) presents results for children.

The pooled estimates under age 15 years were 3.0% (-2.1, 8.4) for single day lags, and 4.6% (-2.2, 12.0) for cumulative lags. Single day lags used were 0 for London and 2 for Paris, and cumulative ones 0-3 for London and 0-2 for Paris.

The reason given for the use of different lags in each city is that local factors like wind direction, size of the city or location of the monitoring sites vary between cities. It is however not clear why lags should differ between children and adults: in London the chosen cumulative lag was 0-1 for adults and 0-3 for children and in Paris the single day lag was 0 for adults and 2 for children. For adults, the pooled estimate using lag 0 in all cities was 2.0% (-1.7, 5.7), and 0.7% (-2.8, 4.5) for lag 1.

When two-pollutant models were considered (Table 4 of the paper, below), the effect of BS disappeared after adjustment for NO2 or SO2, while the effects of these two pollutants were still present after adjustment for BS.

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5.2. THE APHEA2 STUDY

In the APHEA2 study, one article was dedicated to the association between PM10 and respiratory admissions (Atkinson et al, 2001). The methods, including the eight cities/areas included, the study period, PM10 estimation and the statistical model used were the same as for the CVD admission analysis (Le Tertre et al, 2002a).

Four different outcomes were considered, i.e., daily admissions for asthma (ICD9 493) at ages 0-14 and 15-64 years, COPD and asthma (ICD9 490-496) at age 65+ years, and all respiratory disease admissions (ICD9 460-519) at age 65+ years. The authors specify that, wherever possible, emergency admissions resulting in overnight hospital stay were specified, in order to exclude elective admissions and those resulting only in an emergency room visit. However, unlike for CVD admissions, no investigation of the proportion of elective admissions for specific admission diagnoses, and consequent exclusion of diagnoses with high prevalence of elective admissions, was performed.

In the following table (Table 3 of the article) the percent change in daily admissions associated with a 10 µg/m3 increase in PM10 or BS for each city is given, together with the pooled estimates. With few exceptions, the city-specific estimates were positive for all four endpoints, although only for a few of them the confidence interval did not include zero increase. For 5 of the 8 pooled results there was evidence of heterogeneity between cities.

For asthma in children the summary estimates were 1.2% (0.2, 2.3) for PM10 and 1.3% (0.3, 2.4) for BS, while for asthma in adults they were 1.1% (0.3, 1.8) for PM10 and 0.7% (-0.3, 1.8). Thus, for PM10 there was no evidence that children were

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relatively more susceptible than adults to PM-induced asthma exacerbation. In the age group 65+ years, the pooled estimates for COPD plus asthma were 1.0% (0.4, 1.5) for PM10 and 0.2% (-1.3, 1.6) for BS. Corresponding estimates for all respiratory diseases were 0.9 % (0.6, 1.3) and 0.1% (-0.7, 0.9), respectively.

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Two-pollutant models were also fitted for PM10 (Table 4 of the paper, below).

For asthma in children and adults, adjustment for NO2 had the strongest effect on the PM10 estimates, which were substantially reduced. Ozone was the major confounder for COPD plus asthma in elderly people, while no substantial change in the point estimate for all respiratory diseases in the elderly was observed (although the inclusion in the model of correlated variables resulted in inflated standard errors of the estimates).

Finally the effect modification of several city-specific variables was considered. For asthma in children, humidity (inversely), smoking prevalence (inversely) and percent of population over 65 years (directly) reduced the heterogeneity χ2 by over 40%. For the two endpoints considered for the elderly, higher mean ozone levels resulted in stronger PM effects.

5.3. NATIONAL MULTICITY STUDIES

In the same articles in which results for CVD admissions were presented, the French (Eilstein et al, 2004) and the Italian (Biggeri et al, 2005) studies investigated also the association between PM and hospital admissions for respiratory diseases.

The French study found a positive significant association between BS day to day variations and all respiratory admissions in the age group 0-14 years, and no effect at age 65+ years. The Italian study found a direct association between PM10 and respiratory admissions at all ages, with however large heterogeneity between cities.

5.4. FINE AND COARSE PM

The study from the West Midlands conurbation of the UK (Anderson et al, 2001) examined the association between fine (PM2.5) and coarse PM (PM2.5-10) with respiratory emergency admissions. The endpoints considered were daily emergency hospital admissions for respiratory causes (ICD9 460-519) at all ages and in the age groups 0-14, 15-64 and 65+ years, asthma in the age groups 0-14 and 15-64 years and COPD at ages 65+ years (Table 5 of the paper, below).

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For all respiratory causes, significant positive associations were found in the age group 0-14 years for PM10 and BS, and borderline positive associations for PM2.5 and PM2.5-10, although the strongest positive association was found with SO2.

For asthma in children, there were significant direct associations with PM10 and BS, while the association with PM2.5 and PM2.5-10 were not significant (Table 6 of the paper, above). The only other significant association was a negative one between asthma at 15-65 years and coarse PM.

5.5. CONCLUSIONS

In the multicentric European APHEA1 study, an association was reported between NO2 and SO2 exposure and respiratory hospital admissions. In the APHEA2 study several pollutants and respiratory diseases were considered, with positive associations detected for most pollutant-outcome combinations, albeit mostly not significant. Additional support for an association between air pollution, principally gaseous pollutants, and respiratory admissions is provided by a multicentric Italian study.

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6. SHORT-TERM PM EXPOSURE AND OUTPATIENT VISITS

A few studies examined the relation between PM levels and outpatient visits in emergency department or at home, or dispensing of respiratory drugs. Most studies used as outcomes visits for respiratory diseases overall or asthma, although also allergic rhinitis and cardiovascular causes were considered in some studies. These studies are described in Table IV (modified and updated from EPA 2004 Table 8-B3).

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7. ANALYTIC STUDIES ON LONG-TERM PM EXPOSURE AND MORTALITY

In 2003, at the time of the EPA report, only one cohort study from the Netherlands (Hoek et al, 2002) was available. In more recent years, other four studies from Sweden (Rosenlund et al, 2006), Norway (Naess et al, 2007), Germany (Gehring et al, 2006), and France (Filleul et al, 2005) have been published.

The description and results of each of these five studies are shown in Table V. In the following sections the methods and results of the four longitudinal studies are compared.

The Swedish study (Rosenlund et al, 2006) is a population based case-control study on first AMI. Since separate analyses have also been performed for fatal AMI, the study has been included also in this table. Its results, however, will be discussed in chapter VII, together with other studies investigating the association between long-term exposure to PM and CVD morbidity.

7.1. STUDY DESIGNS, SAMPLE SIZE, TIME FRAME AND POPULATION DEFINITION

The Norwegian study (Naess et al, 2007) is a record linkage study based on all inhabitants of Oslo (n=143,842) aged 51-90 years on January 1, 1992 and followed up until 1998.

The study from the Netherlands (Hoek et al, 2002) is a case-cohort study based on a random sample of 5,000 subjects selected from the over 120,000 participants to the Netherlands Cohort Study on Diet and Cancer aged 55-69 years in 1986, recruited from 204 of 714 municipalities with computerized population registries and covered by a cancer registry, who completed a self-administered questionnaire in 1986. Ninety percent of the sample (4,492 subjects) was successfully followed up until 1994.

The German study (Gehring et al, 2006), is based on about 4,800 women aged 50-59 years who participated to several cross-sectional surveys conducted in various towns of North Rhine Westphalia between 1985 and 1994 and followed up until 2002-2003. The overall response rate to the surveys was 70%, and data on follow-up and address were obtained for 97% of the sample.

The study from France (Filleul et al, 2005) is based on the PAARC (Pollution Atmosphérique et Affections Respiratoires) cohort study and includes 14,284 adults residing in 7 French cities, aged 25-59 years at enrollment in 1974 and followed up until 2001 for vital status. Cause of death was available until 1998 for 96% of the sample.

7.2. ASSESSMENT OF EXPOSURE TO PM AND CO-POLLUTANTS

For all the studies, exposure assessment was based solely on the home address, without considering other possible sources of exposure (other locations or occupation). The French study, however, excluded from the sample heads of households who were manual workers, to avoid confounding from other heavy

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exposures. Occupation was controlled for in some studies (see section on statistical model and control of confounding).

Average ambient concentration at the home address over a period of several years was considered as indicator of exposure in all the studies. The follow-up studies evaluated exposure for 1-5 years around the baseline.

Several methods were used for estimating ambient PM concentrations based either on data from air monitor stations placed ad hoc (Filleul et al, 2005) or on air dispersion modeling systems (Hoek et al, 2002; Gehring et al, 2006; Naess et al, 2007), even corrected for distance to a major road (Hoek et al, 2002; Gehring et al, 2006).

Several PM indexes were used, including PM10, PM2.5, BS and TSP. Although other gaseous pollutants were measured in several studies, no mutual adjustments were performed.

7.3. STATISTICAL MODEL AND CONTROL OF CONFOUNDING

Cox proportional hazard models were used in the four longitudinal studies. In general, no other environmental variables were included. Sex and age were controlled for in all the studies. The record linkage study from Norway (Naess et al, 2007) recovered information on education and occupation (manual/non manual) from census data for 77% of the sample. Smoking and education/socioeconomic status were controlled for in most of the other studies, together with other potential confounders (physical activity, diabetes, body mass, diet, occupational exposure).

7.4. MAIN RESULTS

The hazard ratio (HR), as an estimate of RR, for deaths from all causes from the Norwegian record linkage study according to approximate quartiles of long-term PM2.5 exposure are presented in Table 2 of the article (Naess et al, 2007) (below), separately by sex and age at enrollment (51-70 and 71-90 years).

Compared to those in the lowest exposure categories, the HRs were 0.96 (0.89, 1.04), 1.12 (1.03, 1.22) and 1.48 (1.36, 1.60) in subsequent quartiles of exposure for men aged 51-70 years. Corresponding estimates in older men were 0.99 (0.93, 1.06), 1.10 (1.03, 1.17) and 1.19 (1.12, 1.27). Estimates in women were very similar to those of men of the corresponding age group. Adjustment for education and occupational class did not materially modify the results.

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Cause- and sex-specific HRs for PM10 and PM2.5 (and NO2) are presented in Table 3 of article for the age group 51-70 years and in Table 4 for the age group 71-90 years (Naess et al, 2007) (below).

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These results are difficult to interpret for two reasons. First, it is not clear what are the categories compared in the models. In the headings of the table the authors say “quartile increase”. It is not clear whether this means that these are risks for an increase of exposure from one quartile (i.e. the exposure variable was entered as an ordered variable coded 1, 2, 3 or 4 according to the exposure quartile) or whether the forth and first quartiles were compared. In the first and more likely case, Table 2 points to a limitation of this analysis, since there was no increase in risk between the first two quartiles, and the biggest increase was observed between the third and fourth quartiles, particularly for younger subjects. In the second case, half of the

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population (i.e. those in the second and third quartile) would not contribute to the HR estimates.

Moreover, division of the population in four subgroups according to age and sex renders the results difficult to interpret, in particular in the absence of clear justifications and formal tests of heterogeneity between subgroups.

Table 4 of the corresponding paper, below, shows the main results from the Netherlands study (Hoek et al, 2002) according to two different models. In the first model, average regional background concentration of BS and distance of the residence from a major road were entered separately, while in the second model these two were combined by adding a constant to BS exposure estimates for those living near a major road.

Subjects living near a major road had an increased risk of all cause mortality, particularly after adjustment for several confounders and in individuals who had lived 10 years or longer at their 1986 address (RR=1.53, 95% CI 1.01, 2.33). Most of the excess risk observed in total mortality appeared to be attributable to cardiopulmonary causes of death. Additional analyses of the Netherlands study have been reported in an abstract form (Beelen et al, 2007). Using a case-cohort approach, adjusted RRs for an increase of BS by 10 µg/m3 were 1.03 (0.91, 1.17) for all causes except accidents and violence, 1.04 (0.90, 1.20) for cardiopulmonary, 1.16 (0.91, 1.48) for respiratory, 0.99 (0.80, 1.23) for lung cancer, and 1.03 (0.91, 1.16) for non-cardiopulmonary, non-lung cancer mortality. Corresponding RRs in the full cohort analyses, which included confounder information only on age, gender, active smoking and area-level socio-economic status, were 1.05 (1.00, 1.10) for all natural causes, 1.06 (0.98, 1.15) for cardiopulmonary, 1.22 (0.99, 1.49) for respiratory, 1.03 (0.88, 1.20) for lung cancer, and 1.00 (0.96, 1.11) for non-cardiopulmonary, non-lung cancer mortality (Beelen et al, 2007).

In the German study too, the effects of PM and traffic appeared stronger for - or limited to - cardiopulmonary mortality (Gehring et al, 2006). In that study, a similar approach to the Dutch study was used, i.e., background exposure and distance of the residence from a road with >10,000 cars/day were estimated independently. Background exposure was computed as average concentrations for the year of recruitment and for the four years preceding recruitment.

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The adjusted RRs for a 7 µg/m3 increase in PM10 in the baseline year were 1.08 (0.94, 1.25) for all cause mortality, 1.34 (1.06, 1.71) for cardiopulmonary mortality and 0.92 (0.80, 1.10) for non cardiopulmonary non lung cancer mortality (see Table 4 of the corresponding paper, above). When exposure was measured for five years the RR for cardiopulmonary mortality increased to 1.59 (1.23, 2.04). Women living near a major road had a 70% (2, 181) increased risk of dying for cardiopulmonary causes. In the text the authors state that mutual adjustment of air pollution effects and proximity to roads did not change these estimates.

The French study (Filleul et al, 2005) estimated average exposure for the period 1974-76 (see Table 4 of the paper, below). When all 24 areas were included in the analysis, long-term exposure to BS or TSP did not affect the risk of mortality from all non-accidental causes, cardiopulmonary causes or lung cancer, all the RR ranging between 0.97 and 1.01.

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However, the authors repeated the analysis excluding subjects from six areas for which the ratio NO/NO2 (measured in ppb) was more than 3. The reason for this exclusion was that NO is the principal component of the NOx emissions by cars and the high NO/NO2 ratio indicated that the monitoring station was close to a very busy roadside. Thus, the exposure measure was heavily influenced by local traffic and non representative of the mean exposure of the population of the entire area. When the analysis was restricted to 18 areas, the RR for a 10 µg/m3 increase in TSP was 1.05 (1.02, 1.08) for total non-accidental mortality, 1.00 (0.92, 1.10) for lung cancer and 1.06 (1.01, 1.12) for all cardiopulmonary causes. Corresponding estimates for BS were 1.07 (1.03, 1.10), 1.03 (0.92, 1.15) and 1.05 (0.98, 1.12).

7.5. EFFECT MODIFICATION BY AGE, SEX, SOCIOECONOMIC STATUS OR OTHER VARIABLES

As we have already commented, the Norwegian study (Naess et al, 2007) shows all results separately for four subgroups defined by sex and age without however a formal evaluation of differences between subgroups. For total mortality, results appeared similar betweens sexes, and the associations with PM2.5 were stronger in the younger age group, although, mainly based on models for NO2, the authors argue for the opposite: The HRs for all cause mortality in the highest PM2.5 exposure quartile were 1.44 (1.32, 1.58) in younger men and 1.18 (1.10, 1.26) in older men, 1.41 (1.27, 1.57) in younger women and 1.11 (1.05, 1.17) in older women.

The German study (Gehring et al, 2006) was based on women who were of similar age at recruitment, and thus could not investigate modification effects by age and sex. In the text the authors write that they “found modestly stronger NO2 and PM10 effects on all-cause mortality for women with a low SES, for current smokers, and for nonsmokers exposed to environmental tobacco smoke”.

In the French study (Filleul et al, 2005), subgroup analyses by sex, smoking status, occupational exposure to dust, gases and fumes, education and age were shown in a graph (see Figure 2 of the paper, below). No clear differences were observed with age, sex, or smoking. The highest point estimates were observed in more educated or occupationally exposed subjects.

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7.6. COMPARISON OF EUROPEAN WITH LEADING NORTH AMERICAN STUDIES

European studies suggest that mortality from cardiopulmonary diseases is associated with long-term exposure to air pollution, but provide limited evidence that various measures of PM are related to total mortality. This is in apparent contrast with the leading North American studies, consistently providing direct associations between fine particles and total mortality. In the Harvard Six Cities study, 8,096 white participants from various cities of the USA were followed since the mid-1970 to 1998. The adjusted RRs for an increase of PM2.5 of 10 µg/m3 were 1.16 (1.07, 1.26) for total mortality, 1.28 (1.13, 1.44) for cardiovascular diseases, 1.08 (0.79, 1.49) for respiratory, 1.27 (0.96, 1.69) for lung cancer and 1.02 (0.90, 1.17) for other causes (Laden et al, 2006). In the ACS-CPS-II study, that linked air pollution data with the individual data of approximately 500,000 adults from the USA, followed from 1982 to the end of 1998 (Pope et al, 2002) (Pope et al, 2004), the adjusted RRs for an increase of PM2.5 by 10 µg/m3 were 1.06 (1.02, 1.11) for all-cause mortality, 1.12 (1.08, 1.15) for cardiovascular diseases plus diabetes, 0.92 (0.86, 0.98) for respiratory, 1.14 (1.04, 1.23) for lung cancer and 1.01 (0.95, 1.08) for all other causes. In that study, however, an interaction with education was evident. In fact, for subjects in the highest category of education (>high school), no association was found between increasing levels of PM2.5 and total, cardiopulmonary and lung

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cancer mortality. This is in contrast with the findings from the French study (Filleul et al, 2005), where the highest point estimates were observed in more educated subjects. Apart for chance and/or bias, at least part of the discrepancies could be explained by the different PM measure investigated. In fact, most European studies provided data on PM10 only, and not on finer PM.

7.7. CONCLUSIONS

In a Norwegian cohort study, a significant association was reported between PM exposure and mortality, although the interpretation of the results is not straightforward. Mortality was associated with various measures of air pollution in cohort studies from the Netherlands, Germany and France, and the excess risk in these studies was mainly attributed to cardiovascular and respiratory diseases.

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8. ECOLOGIC STUDIES ON LONG-TERM PM EXPOSURE AND MORTALITY

One study compared mortality rates before and after the ban of coal sales in Dublin (Clancy et al, 2002). Given the deterioration of the air quality in the 1980s after a switch from oil to other fuels, mainly bituminous coal for domestic space and water heating, the Irish Government banned the marketing, sale and distribution of bituminous coals within the city of Dublin on September 1990. The Figure 1 of the paper, below, shows the consequent declines in BS and SO2.

Average BS concentrations declined by 35.6 µg/m3 (70%) after the ban.

The authors compared age-adjusted death rates (directly standardized on the 1991 Irish census population) for the 72 months before (Sep 1984 to Aug 1990) and after (Sep 1990 to Aug 1996) the ban.

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Table 2 of the paper, below, presents mortality rates for the two periods, overall and by season, for total non-accidental causes, and for cardiovascular, respiratory and other causes, separately.

Significant decreases were observed for all non-accidental and cardiovascular mortality in all seasons, and the decreases were more marked in winter. Significant decreases were observed for respiratory mortality overall, in winter and spring, while no significant change was observed overall for other causes. The authors concluded that control of PM could substantially diminish daily death. However, it is worth noticing that, during the same period, mortality declined in several European countries. Thus, a causal link between the decline in mortality and the ban of coal sales is far from established. On the other hand, the authors interpreted the fact that the biggest declines were observed in winter, when the use of coal was highest, as suggestive of their hypothesis.

Two studies compared air pollution levels in 1,030 census enumeration districts in Sheffield, UK, to mortality and emergency hospital admission rates from coronary heart disease (Maheswaran et al, 2005b) and stroke (Maheswaran et al, 2005a). For each district a 5-year average PM10 concentration for the period 1994-1999 was computed. The districts were then divided according to quintiles of PM10 concentrations. The mean PM10 concentration in the highest quintile was 23.3 µg/m3, and 16.0 µg/m3 in the lowest one. Mortality and emergency hospitalization rates

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were then computed for the districts’ quintiles. For coronary heart disease, the rate ratios (adjusted for sex, age, deprivation and smoking prevalence) for the highest quintile compared to the lowest one were 1.08 (0.96, 1.20) for mortality and 1.01 (0.90, 1.14) for hospital admissions. Corresponding values for stroke were 1.33 (1.14, 1.56) and 1.13 (0.99, 1.29).

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9. LONG-TERM PM EXPOSURE AND CARDIOVASCULAR MORBIDITY

Table VII summarizes results of studies on the effect of long-term exposure to PM and cardiovascular morbidity.

A population-based case-control study on 1,393 cases of first AMI and 1,870 population controls resident in Stockholm county, aged 45-70 years was conducted between 1992 and 1994 (Rosenlund et al, 2006). Response rates to the mailed questionnaire varied between 70-85% depending on sex and case-control status. For each subject, exposure to PM10 and PM2.5 was reconstructed from 1960 to a year prior to enrollment (1992-1994), i.e., for over 20 years, using data on traffic around the home address only. Only data for long-term exposure to PM10 were used in the analysis, given the high correlation between PM10 and PM2.5 (r=0.998).

Logistic regression models adjusted for the matching variables, i.e. age, sex and hospital catchment area, and smoking, physical inactivity, diabetes and SES were used to compute odds ratios (OR). Hypertension, body mass, job strain, diet, passive smoking, alcohol and coffee intake and occupational exposure to motor exhaust and other combustion products were also evaluated, but did not appear to confound the relation with PM.

Table 2 of the article (below) presents the main results of the study.

Overall, there was no association between PM10 and AMI (OR=1.00, 95% CI 0.79, 1.27). The point estimate was above unity for fatal cases (OR=1.39, 95% CI 0.94, 2.07) and below unity for non fatal cases (OR=0.92, 95% CI 0.71, 1.19) although none of these estimates was statistically significant. A borderline significant association was found when fatal cases were further restricted to those who died out of hospital (OR=1.84, 95% CI 1.00, 3.40). These were 84 out of 1,357 cases (6%). Although the authors interpret this finding as supportive of a possible association between air pollution exposure and mortality, random variation in small subgroups cannot be excluded.

Moreover, it is not clear how covariates were measured for fatal cases in general, and specifically in this group that died out of hospital. If proxy interviews were used for deceased cases, and direct interviews for controls, the effect of differential collection of covariates has to be considered.

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The two ecologic studies from Sheffield, UK, discussed in the previous chapter found rate ratios of 1.01 (0.90, 1.14) for emergency hospital admissions for coronary heart disease and of 1.13 (0.99, 1.29) for emergency hospital admissions for stroke for subjects living in census enumeration districts with the highest levels of PM10 concentrations, as compared to the lowest ones.

Two studies investigated the association between long-term exposure to PM and prevalence of coronary or ischemic heart disease (Solomon et al, 2003; Hoffmann et al, 2006). Being based on prevalence data, these studies should be interpreted with caution.

A cross sectional postal survey on 1,166 women aged 45 years or more was conducted in 11 wards in the UK for which 30 years long concentration data on BS were available (Solomon et al, 2003). After adjustment for potential confounders, women living in areas with high BS concentrations did not report higher prevalence of ischaemic heart disease, as compared to women living in low BS areas (OR=1.00, 95% CI 0.7, 1.4).

Another study used baseline data from a newly started cohort study on 4,814 subjects aged 45-75 years from three large adjacent cities in the Rhein-Rhur region, Germany, to investigate the relation between background PM2.5 exposure, residence close to a major road, and prevalence of coronary heart disease (Hoffmann et al, 2006). After adjustment for several potential confounders, the OR for those with high traffic exposure was 1.75 (1.16, 2.62), and for background PM2.5 exposure 0.55 (0.14, 2.11), although the measurement unit for the latter OR is not given.

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10. LONG-TERM PM EXPOSURE AND RESPIRATORY MORBIDITY OR SYMPTOMS

Many European studies have investigated the relation between PM and respiratory symptoms (Table VIII, modified and updated from EPA 2004 Table 8B8). The majority of these studies were on children, but some also in adults. Several different endpoints have been considered.

10.1. LONG-TERM PM EXPOSURE AND ASTHMA IN CHILDREN

A study from the Netherlands (Brauer et al, 2002) recruited about 4,000 children (during the seconds trimester of pregnancy) and evaluated the development of respiratory infections and asthmatic and allergic symptoms using questionnaires completed by the parents when the children were 2 years old. Outdoor concentrations of traffic-related PM2.5 and soot at the home address of the children were estimated by means of a validated model. At two years of age, 176 children (5%) had developed physician-diagnosed asthma. After adjustment for several potential confounders, the OR for an increase equal to the IQR (3.2 µg/m3 for PM2.5 and 2x10-5/m for soot, corresponding to 2.9 µg/m3 of elemental carbon) were 1.12 (0.84, 1.50) for PM2.5 and 1.12 (0.88, 1.43) for soot.

A cross-sectional survey conducted in France (Penard-Morand et al, 2005) on a random sample of 6,672 schoolchildren aged 9-11 years found an adjusted OR of asthma during the past year for an increment of PM10 by 10 µg/m3 of 1.23 (0.77, 1.95), that was virtually unchanged after further adjustment for SO2.

Among the 3,193 French children aged 5-9 years and included in the PAARC survey (Baldi et al, 1999), 195 (6%) were found to be asthmatic. The adjusted OR for an increase of 50 µg/m3 in annual mean concentrations was 0.99 (0.81, 1.20) for TSP and 1.08 (0.85, 1.38) for BS.

10.2. LONG-TERM PM EXPOSURE AND LUNG FUNCTION IN CHILDREN

Spirometry was performed twice a year between 1994 and 1997 in 975 Austrian schoolchildren of grades 2-3 at baseline (Horak et al, 2002). After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM10 by 10 µg/m3 was associated with a decrease in FEV1 growth of 84 mL yr-1 and 329 mL s-1 yr-1 for MEF25–75. No association was found for FVC or in winter (see Table 4 of the paper below).

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A study from the UK (Kulkarni et al, 2006) obtained airway macrophages and assessed the carbon content from 64 healthy children. PM10 concentrations near the home address, FEV1 and FVC were also measured. They found that an increase of 1.0 μg/m3 in modeled primary PM10 was associated with a 0.10 μm2 (0.01, 0.18) increase in the carbon content of airway macrophages. Increased primary PM10 was inversely associated with the percentage of the predicted FEV1 (P = 0.04) and the FEF25–75 (P = 0.05). After adjusting for the carbon content of PM10, the carbon content of airway macrophages remained inversely associated with the percentage of the predicted values of FEV1, FVC, and FEF25–75 (P = 0.02, P = 0.04, and P = 0.02, respectively), whereas PM10 was no longer significantly associated with lung function (Table 2 of the paper, below).

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Finally, a study from eastern Germany (Frye et al, 2003) conducted three cross-sectional surveys of lung function in schoolchildren aged 11-14 between the early and late 1990s, and found that lung function of children has increased, while TSP and other pollutant levels had decreased during the study period.

10.3. LONG-TERM PM EXPOSURE AND RESPIRATORY SYMPTOMS IN CHILDREN

Two cohort studies investigated the issue.

The cohort of about 4,000 children from the Netherlands, that has been already discussed for asthma (Brauer et al, 2002), evaluated the development of respiratory infections and asthmatic and allergic symptom using questionnaires completed by the parents when the children were 2 years old.

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Outdoor concentrations of traffic-related PM2.5 and soot at the home address of the children were estimated by means of a validated model. Adjusted OR for the various symptoms and diseases were computed for an increase in exposure equal to the IQR i.e. 3.2 µg/m3 for PM2.5 and 2x10-5/m for soot, corresponding to 2.9 µg/m3 of elemental carbon. The results are presented in Table 4 of the article (above). Statistically significant increases in risk were found between PM2.5 and ear, nose and throat infections (OR=1.20 95% CI 1.01, 1.42) and doctor-diagnosed flu/serious cold (OR=1.00, 1.27). For soot, the only significant association was with ear, nose and throat infections (OR=1.15 95% CI 1.00, 1.33).

A cohort of 4,400 children aged 1-5 years was recruited in Leichestershire, UK in 1998 (Pierse et al, 2006). Parents filled in a respiratory symptom questionnaire at baseline and again in 2001. Exposure to primary PM10 was calculated from the home address using a dispersion model based on estimated traffic emissions from traffic flow data. Adjusted OR for an increase in primary PM10 of 1 µg/m3 were computed.

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The prevalence of symptoms was first evaluated cross-sectionally in the two surveys (Table 2 of the paper, above). The authors then evaluated the OR of developing symptoms in the study period (Table 3 of the paper, below). The ORs were 1.62 (1.31, 2.00) for cough without a cold, 1.19 (0.96, 1.47) for night time cold, and 1.42 (1.02, 1.97) for wheeze.

A number of cross-sectional studies investigated the association between exposure to PM and prevalence of a number of respiratory symptoms. These studies are often difficult to interpret, given the unclear time relation between exposure and outcome and the high number of outcomes considered, and consequent problems related to multiple testing. Their results are summarized in Table VIII.

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10.4. LONG-TERM PM EXPOSURE AND RESPIRATORY MORBIDITY OR SYMPTOMS IN ADULTS

A random sample of about 7,000 persons residing in 21 centres in 10 countries, who participated to the European Community Respiratory Health Study I (ECRHS I) in 1991-93, were re-interviewed in 2000-2002 to investigate the onset of symptoms for chronic bronchitis (response rate 65%). Table 4 (below) of the article presents the main findings.

No association was found between centre level of PM2.5 and chronic phlegm prevalence at follow up. The ORs were 0.97 (0.70, 1.35) for males and 0.99 (0.85, 1.17) for females, but the measurement unit was not given. A constant exposure to traffic was associated with prevalence of chronic phlegm in women (OR=1.86, 95% CI 1.24, 2.77), but not in men (OR=0.88, 95% CI 0.56, 1.38).

The PAARC study (Baldi et al, 1999) collected data also on 20,310 French adults aged 25-59 years, 1,261 (6%) of whom were found to be asthmatic. No association

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was found between long-term exposure to TSP (OR for an increase of 50 µg/m3=1.01, 95% CI 0.92, 1.11) or BS (OR=1.07, 95% CI 0.96, 1.20).

The SAPALDIA study (Zemp et al, 1999) is a cross-sectional investigation in a random sample of 9,651 Swiss adults aged 18-60 years. Asthma prevalence was inversely associated with TSP and PM10 in never smokers, while some respiratory symptoms showed a positive association with PM10.

A cross-sectional postal survey on 1,166 women aged 45 years or more was conducted in 11 wards in the UK for which 30 years long concentration data on BS were available (Solomon et al, 2003). After adjustment for potential confounders, women living in areas with high BS concentrations reported lower prevalence of asthma, as compared to women living in low BS areas (OR=0.7, 95% CI 0.5, 1.0). Productive cough was not associated with BS (OR=1.0, 95% CI 0.7, 1.5).

Three studies investigated the relation between air pollution and lung function in adults. In the SAPALDIA study (Ackermann-Liebrich et al, 1997) significant inverse effects were found between PM10 and FVC and FEV1 in the whole population and separately between never, ex and current smokers. The Health Survey for England (Wheeler and Ben-Shlomo, 2005), including 39,251 participants aged 16-79 years, found that low social class and poor air quality were independently associated with decreased lung function (FEV1), but not asthma prevalence. For men, but not for women, the effects of air pollution on lung function appeared more marked in lower social classes. In a series of cross-sectional surveys on 4,757 women living in the Rhine-Ruhr Basin in Germany (Schikowski et al, 2005), a 7 µg/m3 increase in PM10 was associated with a 5.1% (2.5, 7.7) decrease in FEV1, a 3.7% (1.8, 5.5) decrease in FVC and an OR of 1.33 (1,03, 1.72) for COPD.

Finally, among the first 3,904 participants to the EPIC study residing in Athens, those living in the most polluted areas had a two-fold increase in prevalence of chronic bronchitis, emphysema or COPD (Karakatsani et al, 2003).

10.5. CONCLUSIONS

Three studies on PM exposure and asthma in children from the Netherlands and France reported weak, non-significant associations. Two studies on PM exposure and lung function in children from Austria and UK reported associations with some of the indicators of lung function, which were not confirmed by a further study from eastern Germany. Two cohort studies from the Netherlands and UK reported significant associations with various symptoms.

Studies in adults did not provide consistent evidence of an association between PM exposure and chronic bronchitis or asthma. Studies on air pollution and lung function, on the other hand, reported positive results.

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11. LONG-TERM PM EXPOSURE AND CANCER

Table IX summarizes data on long-term PM exposure and cancer. Most studies considered lung cancer. Data for other neoplasms are sparse. A few studies considered exposure to traffic and childhood cancer, although the underlying etiologic hypothesis is in general connected to benzene, and not PM, exposure. They are listed in Table IX, but not discussed here.

11.1. ANALYTIC STUDIES ON LUNG CANCER

Three (Hoek et al, 2002; Filleul et al, 2005; Naess et al, 2007) of the four longitudinal studies that were discussed in the chapter on long-term exposure to PM and mortality (chapter V) also presented data on lung cancer mortality.

In the cohort study from the Netherlands (Hoek et al, 2002) 60 deaths from lung cancer were recorded. The adjusted relative risk for an increase of 10 µg/m3 in BS was 1.06 (0.43, 2.63), and 1.25 (0.42, 3.72) for a 30 µg/m3 increase in NO2. The number of cases was too small to compute a risk for the indicator variable of living near a major road. Preliminary results of new analyses of the Netherlands study showed that the adjusted RRs for an increase of BS by 10 µg/m3 was 0.99 (0.80, 1.23) in the case-cohort analysis, and 1.07 (0.96, 1.19) in the full cohort analysis, based on 1,935 lung cancer deaths (Beelen et al, 2007).

In the Norwegian record linkage study (Naess et al, 2007), risks were computed separately by sex and age group at baseline (51-70 and 71-90 years), for lung cancer too. For men, no significant excess was found, and the estimated RR for a “quartile increase” in PM10 was 1.07 (0.97, 1.18) in both age groups. Conversely, significantly increased risks were found for women in both age groups: 1.27 (1.13, 1.43) for younger and 1.17 (1.03, 1.33) for older women. Estimates for PM2.5 were virtually identical to those for PM10.

In the French PAARC study cohort (Filleul et al, 2005) 178 deaths from lung cancer were recorded, and the risk of lung cancer associated to an increase in exposure of 10 µg/m3 of TSP was 0.97 (0.94, 1.01) when all 24 areas were considered, and 1.00 (0.92, 1.10) when the analysis was restricted to subjects living in the 18 areas with the ratio NO/NO2 <3. Corresponding values for BS were 0.97 (0.93, 1.01) and 1.03 (0.92, 1.15). The only significant results for lung cancer was for NO2, when the analysis was restricted to 18 areas (RR=1.48, 95% CI 1.05, 2.06).

A nested case-control study within EPIC (European Prospective Investigation on Cancer and Nutrition) cohort also investigated the association between long-term exposure to PM10 and the risk of lung cancer (Vineis et al, 2006). The over 500,000 healthy volunteers aged 35-74 of the EPIC cohort were recruited in 10 European countries between 1993 and 1998. Identification of cancer cases was mostly based on cancer registries during a median follow-up time of 7 years. A nested case-control study was conducted within the cohort. For each lung cancer case within selected areas, who was a non smoker or an ex smoker since more than 10 years, 3 controls were selected, matched on sex, age, smoking status, country of recruitment and follow-up time. Assessment of exposure to traffic-related air pollution was made for the period 1990-1999 using available data from monitoring stations from the various areas under study. Distance of the home from a major road was also computed. Given the different availability of exposure data from the various areas, analyses were based on different number of cases. Of the 271 cases

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and 737 controls included in the study, data on PM10 exposure were available for 113 cases and 312 controls.

Table IV of the article (below) shows the results for pollutant concentrations. After adjustment for the matching variables, the OR was 0.91 (0.70, 1.18) for an increase in PM10 of 10 µg/m3 and 0.98 (0.66, 1.45) for exposures over 27 µg/m3, compared to less than 27 µg/m3. The marked change observed when cotinine was added to the model was interpreted by the authors as an effect of random variation due to small numbers.

The OR was 1.38 (0.87, 2.19) for those living near a heavy traffic road.

A case-control study on lung cancer was conducted among men who died in Trieste, Italy, between 1979 and 1981 and between 1985 and 1986 (Barbone et al, 1995). Cases were 755 men who died of lung cancer, and controls 755 men who had died for other causes, non COPD nor various cancers of the upper aerodigestive tract, urinary tract, pancreas, liver or gastrointestinal system. Total daily deposition of particulate measured at the closest monitor station from the last subject’s residence was used as measure of the subject’s exposure. Compared to <0.18 g/m2/day of deposition of particulate the OR was 1.1 (0.8, 1.5) for 0.18-0.30 and 1.4 (1.1, 1.8) for >0.30 g/m2/day.

Table VIII/1 shows results of the various analytical studies.

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Table VIII/1 Analytic studies investigating the relation between long-term PM exposure and lung cancer.

Study, design Sex, age at recruitment

No. of cases

Risk indicator, measurement unit

Relative risk (95% CI)

Barbone et al., 1995, case-control, Italy

M 755 Particulate deposition 0.18-0.30 vs <0.18 g/m2/day

1.1 (0.8-1.5)

Particulate deposition >0.30 vs <0.18 g/m2/day

1.4 (1.1-1.8)

Hoek et al., 2002, NLCS cohort, the Netherlands

MF, 55-69 60 BS, 10 µg/m3 1.06 (0.43-2.63)

Beelen et al., 2007 MF, 55-69 1,935 BS, 10 µg/m3 1.07 (0.96-1.19) Filleul et al., 2005, PAARC cohort, France

MF, 25-59 178 TSP, 10 µg/m3 (24 areas) 0.97 (0.94-1.01)

TSP, 10 µg/m3 (18 areas) 1.00 (0.92-1.10) BS, 10 µg/m3 (24 areas) 0.97 (0.93-1.01) BS, 10 µg/m3 (18 areas) 1.03 (0.92-1.15) Vineis et al., 2006, case-control nested in the EPIC cohort, 7 European countries

MF, 35-74 Non- or ex-

smokers 113 PM10, 10 µg/m3 0.91 (0.70-1.18)

PM10 >27 vs <27 µg/m3

0.98 (0.66-1.45)

Naess et al., 2007, cohort, Norway

M, 51-70 449 PM10, quartile increase 1.07 (0.97-1.18)

PM2.5, quartile increase 1.07 (0.97-1.18) F, 51-70 295 PM10, quartile increase 1.27 (1.13-1.43) PM2.5, quartile increase 1.27 (1.13-1.43) M, 71-90 424 PM10, quartile increase 1.08 (0.98-1.20) PM2.5, quartile increase 1.07 (0.97-1.18) F, 71-90 285 PM10, quartile increase 1.17 (1.03-1.33) PM2.5, quartile increase 1.16 (1.02-1.32)

Three other studies on the association of air pollution and lung cancer did not directly measure the effect of PM. A case-control study from Poland (Jedrychowski et al, 1990) found ORs of 1.00 (0.75, 1.33) and 1.46 (1.06, 1.99) for subjects with intermediate and high exposure to air pollution, compared to those with low exposure, based on an index combining TSP and SO2 levels. A case-control study from Sweden (Nyberg et al, 2000) did not find significant associations with NO2 (OR=1.05, 95% CI 0.93, 1.18) or SO2 (OR=1.00, 95% CI 0.96, 1.05). A cohort study from Norway (Nafstad et al, 2003) found a RR of 1.08 (1.02, 1.15) for a 10 µg/m3 increase in exposure to NO2. No association was found for SO2 (OR=1.01, 95% CI 0.94, 1.08).

The evidence concerning the association between long-term PM exposure and lung cancer risk is still scanty. Some studies were based on small numbers of cases. The Norwegian linkage study (Naess et al, 2007) included a large number of cases, but

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did not have information on possible confounding factors, particularly smoking. Moreover, an association was found only for women, but not for men, in the absence of a plausible explanation.

In general, the potential influence of residual confounding by smoking must always be taken into account when dealing with weak associations for lung cancer.

11.2. ECOLOGIC STUDIES ON LUNG AND OTHER CANCERS

A study (Nawrot et al, 2007) found a correlation of 0.57 (p=0.028) between age and smoking standardized lung cancer mortality rates in men and annual mean PM2.5 concentrations in 15 European countries. No significant association was found in women (r=0.37, p=0.18).

No clear evidence for an association between residence along main roads and the incidence of cancer in adults was found in Amsterdam (Visser et al, 2004). Overall, cancer incidence in the area around Amsterdam Schipol Airport was similar to national incidence (Visser et al, 2005). A study from northern Italy (Parodi et al, 2005) investigated lung cancer incidence near a coke oven plant, finding no clear excess risk.

11.3. STUDIES ON AIR POLLUTION AND CANCER IN CHILDREN

A few studies evaluated the association between exposure to traffic and childhood cancer, yielding conflicting results (Raaschou-Nielsen et al, 2001; Crosignani et al, 2004; Knox, 2005; Knox, 2006). The main etiologic hypotheses, however, are related to exposure to benzene and polycyclic aromatic hydrocarbons, rather than to PM.

11.4. COMPARISON OF EUROPEAN WITH LEADING NORTH AMERICAN STUDIES

The findings of European studies on PM and lung cancer are not consistent, nor was a clear pattern of risk observed. More important, no clear association emerged in the major European cohort studies including measures of PM exposure. This is at apparent variance with findings from major US studies, which reported direct associations between fine particles and lung cancer mortality. In fact, the adjusted RRs for lung cancer mortality for an increase of PM2.5 by 10 µg/m3 were 1.27 (0.96, 1.69) in the Harvard Six Cities study (Laden et al, 2006), and 1.14 (1.04, 1.23) in the ACS study (Pope et al, 2002). In the ACS study, the association with PM2.5 was limited to men, in agreement with the AHSMOG study, a cohort based on 6,338 nonsmoking white Californian adults and 36 incident lung cancer cases, which found that the RR for an IQR increase of mean concentrations of PM10 was 5.21 (1.94, 13.99) in men. The corresponding estimate for women was not significant and ranged between 1.0 and 1.2 (Beeson et al, 1998). This is in apparent contrast with the findings from the Norwegian record linkage study (Naess et al, 2007), where no significant excess risk was found for men, while there was a positive association in women.

However, most European studies provided data on PM10 only, and not on finer particulates. Other limitations of exposure measurement may account for at least part of these apparent discrepancies.

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11.5. CONCLUSIONS

Five analytical epidemiological studies from Europe provided results on various measures of particulate matter (PM) and lung cancer. A case-control study from Trieste, Italy found that, compared to <0.18 g/m2/day of deposition of particulates, the RR was 1.1 (0.8, 1.5) for 0.18-0.30 and 1.4 (1.1, 1.8) for >30 g/m2/day. In a cohort study from the Netherlands the RR was 1.06 (0.43, 2.63) for an increase of 10 µg/m3 in black smoke. In a French cohort study the RR of lung cancer associated with an increase in exposure of 10 µg/m3 of total suspended particulate (TSP) was 0.97 (0.94, 1.01). In a nested case-control study within a multicentric European cohort the RR was 0.91 (0.70, 1.18) for an increase in PM10 of 10 µg/m3 and 0.98 (0.66, 1.45) for exposures over 27 µg/m3, compared to less than 27 µg/m3. In a Norwegian record linkage study no significant excess risk was found for men, while there was an association in women. A few other studies considered indirect indicators of air pollution, and some ecological studies linked information on air pollution and cancer incidence or mortality. Although some of the latter studies reported positive associations, various limitations in their design hinder a causal inference.

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12. DISCUSSION AND RECOMMENDATIONS FOR FUTURE STUDIES

12.1. STUDIES ON SHORT-TERM EXPOSURE

Given the availability in several areas of data on daily PM concentrations, and of mortality, and in some instances, hospital admissions, several studies have investigated the association between day-to-day variations in PM concentrations and mortality or emergency hospital admissions. Many of these studies, however, have limitations, either because they were based on small populations or had questionable statistical analysis, which in several instances tended to maximize the investigated association. The latter would affect results of a systematic reanalysis of published studies, and the computing of a pooled measure of association. The use of different measures of PM (PM10, BS, TSP etc.) would further complicate the combination of results from various studies. A pooled re-analysis of various studies, based on the original data, and not on published material, would be more informative and valid, although it would require a great effort.

The APHEA2 study is the largest study on the relation between short-term PM exposure and mortality, and provides the best estimate of the relation between PM10 and day-to-day mortality in Europe. The data of the APHEA2 study were based on a large population from several different areas in Europe, and have been thoroughly re-analyzed to evaluate the influence of different statistical models, the medium-term effects of PM (up to 40 days), and the modification effects of some city characteristics, such as temperature or humidity, but also the percentage of people aged >65 years or of smokers.

Although age at death is, with sex, the only individual characteristic readily available from death certification data, the modifying effect of age on the relation between short-term PM exposure and mortality/morbidity has not been fully clarified. The data from the APHEA2 study suggest that the effect of air pollution is larger at older ages. Deaths in younger age groups are relatively rare, and even the largest study, i.e., the APHEA2, had problems with small numbers in some age categories. Only the combination of many datasets, either within Europe, or including studies from other areas of the world, would provide sufficient power to investigate the effects of air pollution in specific age groups, in particular when specific causes of death are investigated.

The issue of confounding by individual characteristics should not be a major issue, since, in time series data, comparisons are made from one day to another, using the same background populations. In the few studies that have analyzed data using a case-crossover design in addition to a time series approach, the results were comparable.

Scant or inadequate information is available in Europe on modification of the effects of air pollution exerted by individual variables (other than age and sex), e.g. socioeconomic status (SES), lifestyle habits (e.g. smoking), underlying medical conditions (e.g. COPD, coronary disease, diabetes), occupational exposures etc. In Rome a case-crossover design investigated the modification effect of SES using two area-based SES indicators, derived from census data (Forastiere et al, 2005). Although yielding interesting results, that analysis was based on small numbers and on a single population. That type of analysis was based on routinely collected data, and could, in principle, be extended to other datasets.

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Information on the separate effects of coarse, fine and ultrafine PM is still limited. Given that more and more areas within Europe have, in recent years, started the measurement of fine and/or ultrafine PM, it is likely that in the next years several studies will investigate the effects of coarse, fine and ultrafine PM separately. This should be the case, for example, of the HEAPSS study. In the cities included in this study, PNC measurements have started in 2002. In a recent publication, PNC values for a previous period have been estimated retrospectively. New data from the HEAPSS study, from more recent periods and based on actual measurements of PNC, should be available in the next future. Investigations aimed at separating the effects of PM of different diameters will have to deal with the problem of the analysis of highly correlated variables, a problem which has also arisen in the investigation of several correlated pollutants, e.g. PM, NO2, CO and SO2.

As of now, very few results are available from central and eastern European countries.

12.2. STUDIES ON LONG-TERM EXPOSURE

Very few studies have investigated the long-term effects of PM exposure on health. Ecologic studies may be suggestive and hypothesis generating, but, given the potential biases inherent in their design, they cannot provide a solid base for inference.

Record linkage studies, such as the one recently published from Norway (Naess et al, 2007) may include a high number of cases, but the lack of individual variables, first of all smoking habit, renders this type of study difficult to interpret.

Only a limited number of analytic studies have been conducted so far. Many of these were based on cohorts designed for different purposes, which have exploited the availability of PM concentration data in the area under study. This has led to studies that were often based on small numbers, often with exclusions of parts of the study population for which exposure data could not be retrieved.

It is possible that for other longitudinal studies data on exposure could be retrieved and analyzed, but limited availability of reliable data on relevant exposures limits the usefulness of this approach. Thus, only the design of ad hoc studies could provide new insights on the issue.

A somewhat less attractive approach is the pooling of existing cohorts, given the heterogeneity of information on variables used to reconstruct air pollution exposure indicators and on potential confounders. Although technically feasible and relatively inexpensive, it is unclear whether this approach would provide more informative data on long-term effects of air pollution than traditional meta-analyses of already published data. Therefore, the establishment of new multicentric cohorts in Europe remains an appealing approach to investigate long-term effect of air pollution in this region.

In short-term time series, comparisons are ideally made between different days within individuals, and adjustment for day of week and holidays is often performed. In contrast, studies on long-term exposure are necessarily based on comparisons between individuals, and on cumulative exposure assessment. Misclassification of exposure is likely to occur and to affect results. To comment about the different models used for attributing exposure at a certain address is beyond the scope of this report. In almost all the studies conducted so far, the exposure to ambient PM

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has been estimated only on the base of the subject’s home address. No additional information was available on characteristics of the home (e.g. floor of residence) or of the subject’s exposure pattern. Collecting and combining information on hours spent at home, at work, outdoors etc. during the day could improve individual estimates of long-term exposure. The collection of data on potential confounders specifically for the analysis of the association between PM exposure and mortality/morbidity would also provide important additional information.

12.3. RECOMMENDATIONS FOR FUTURE RESEARCH ON HEALTH EFFECTS OF AIR POLLUTION IN EUROPE

Previous studies on short-term effects of air pollution in Europe allow a general quantification of the risks. However, information on the possible confounding or modifying effect of covariates, and mainly data on course, fine and ultrafine particles is limited. Still, with the exception of Central and Eastern Europe, where few data are available, further research on short-term effects of air pollution should not be given high priority.

Only a limited number of analytic studies have been conducted in Europe on long-term effects of air pollution, and these were mainly cohorts designed for different purposes. Their ability to provide valid results was limited by sub-optimal strategies for exposure assessment leading to misclassification, low statistical power, and heterogeneity of approaches. While it is possible that additional exposure data can be retrieved for these and other existing longitudinal studies, it is uncertain whether this approach would lead to major advances. In any case, priority should be given to the co-ordination and harmonization of exposure data in existing cohorts.

The establishment of new studies represents the preferred strategy to provide new insights on long-term effects of air pollution. In areas where estimation of long-term PM exposure could be reconstructed, the case-control design should be considered. The design and implementation of new cohort studies would provide, in the long-term, the most reliable information, but would require great effort in terms of time and resources. Such new studies would rely on uniform methods to measure air pollutants, and be based on an increased number of new measuring stations. Participants should be periodically re-contacted and in addition to information on possible outcomes, new information on exposure based on uniform methodology should be collected. Such new cohorts should give priority to the inclusion of populations from Central and Eastern Europe, where air pollution is higher and adverse health effects may be detected sooner than in less polluted areas of Europe.

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ason

al

cycl

es,

day-

of-w

eek,

in

fluen

za

epid

emic

, ho

liday

s, t

empe

ratu

re a

nd h

um

idity

. F

inal

ana

lysi

s do

ne w

ith a

utor

egre

ssiv

e P

oiss

on

mod

els

to

allo

w

for

ove

rdis

pers

ion

an

d au

toco

rrel

atio

n. P

ollu

tion

effe

cts

exa

min

ed

at 0

th

roug

h 3

day

lags

an

d m

ulti-

day

ave

rage

s th

ereo

f. W

hen

city

-spe

cific

co

effic

ient

s w

ere

te

sted

to

be

ho

mog

eneo

us,

over

all

estim

ates

w

ere

ob

tain

ed

fixed

ef

fect

s m

odel

s.

Whe

n

sign

ifica

nt h

eter

ogen

eity

wa

s pr

esen

t, so

urc

e of

he

tero

gene

ity s

ough

t by

exa

min

ing

a pr

edef

ined

lis

t of

ci

ty-s

pec

ific

varia

ble

s,

incl

udin

g an

nual

an

d se

ason

al m

eans

of

pollu

tion

and

wea

ther

va

riabl

es,

num

ber

of

mon

itorin

g si

tes,

co

rrel

atio

n be

twee

n m

easu

rem

ents

fr

om

diffe

rent

si

tes,

ag

e-st

anda

rdiz

ed

mor

talit

y,

prop

ortio

n of

el

derly

pe

ople

, sm

okin

g pr

eval

ence

, a

nd g

eogr

aphi

c di

ffere

nce

(Nor

th-

Sou

th,

Eas

t-W

est)

. A

ran

dom

effe

cts

mod

el w

as

fit w

hen

hete

roge

neity

cou

ld n

ot b

e ex

plai

ned.

Sub

stan

tial

varia

tion

in

pollu

tion

leve

ls

(win

ter

mea

n S

O2

rang

ed f

rom

30

to 3

30

µg/

m3 ),

clim

ate,

and

sea

sona

l pat

tern

s w

ere

ob

serv

ed

acro

ss

citie

s.

Sig

nific

ant

hete

roge

neity

was

fou

nd f

or t

he e

ffect

s of

B

S

and

SO

2,

but

only

th

e se

para

tion

betw

een

we

ster

n an

d ce

ntra

l-eas

tern

E

urop

ean

citie

s re

sulte

d in

m

ore

hom

ogen

eous

su

bgro

ups.

S

igni

fica

nt

hete

roge

neity

for

SO

2 re

mai

ned

in w

est

ern

citie

s. C

umul

ativ

e ef

fect

s of

pro

long

ed (

two

to

fo

ur

days

) ex

posu

re

to

air

pollu

tant

s re

sulte

d in

est

imat

es c

ompa

rabl

e w

ith t

he

one

day

effe

cts.

The

effe

cts

of b

oth

SO

2 an

d B

S w

ere

str

onge

r du

ring

the

sum

mer

an

d w

ere

inde

pend

ent.

Tot

al m

orta

lity

exce

ss d

eath

s in

si

ngle

day

for

wes

tern

Eur

opea

n

citie

s:

BS

(pe

r 25

µg

/m3 ):

1.4

% (

1.0,

1.8

) P

M10

(pe

r 50

µg/

m3 ):

2%

(1

, 3

)

In

cent

ral/e

aste

rn

Eur

opea

n

citie

s,

BS

(p

er

25

µg/

m3 ):

0.

3%

(0.0

5, 0

.5).

Sam

oli

et

al.

(200

1)

(Sam

oli e

t al,

2001

) A

PH

EA

1

citie

s (s

ee

Kat

souy

anni

(1

997)

(K

atso

uyan

ni e

t al

, 19

97)

At

lea

st

five

year

s be

twee

n 19

80-1

992.

The

P

M l

evel

s ar

e th

e sa

me

as

tho

se i

n K

atso

uyan

ni

et

al.

(199

7)

(Kat

souy

anni

et

al

, 19

97).

In o

rder

to

furt

her

inve

stig

ate

the

sour

ce o

f th

e re

gion

al

hete

roge

neity

of

P

M

effe

cts,

an

d to

ex

amin

e th

e se

nsiti

vity

of

the

RR

s, t

he A

PH

EA

da

ta w

ere

re-a

naly

zed.

Unl

ike

prev

ious

mod

el in

w

hic

h si

nuso

idal

ter

ms

for

seas

onal

con

trol

and

po

lyno

mia

l te

rms

for

wea

ther

, th

e in

vest

igat

ors

this

tim

e us

ed

a G

AM

mo

del

with

sm

ooth

ing

te

rms

for

seas

onal

tre

nd a

nd w

eath

er,

whi

ch i

s m

ore

com

mon

ly u

sed

appr

oac

h in

rec

ent

year

s.

The

est

imat

ed R

Rs

for

cent

ral-e

aste

rn c

ities

w

ere

lar

ger

than

tho

se o

bta

ined

fro

m t

he

prev

ious

m

odel

. A

lso,

re

stric

ting

the

anal

ysis

to

day

s w

ith c

once

ntra

tion

< 1

50

µg/

m3

furt

her

redu

ced

the

diffe

renc

es

betw

een

the

w

este

rn

and

cent

ral-e

aste

rn

Eur

opea

n ci

ties.

The

aut

hors

con

clud

ed t

hat

part

of

the

hete

roge

neity

in t

he e

stim

ated

air

pollu

tion

effe

cts

betw

een

w

este

rn

and

ce

ntra

l ea

ster

n ci

ties

in

prev

ious

pu

blic

atio

ns

wa

s ca

used

by

the

sta

tistic

al

appr

oach

and

the

data

ran

ge.

Tot

al

mor

talit

y pe

r 50

µ

g/m

3 of

B

S; G

AM

app

roac

h:

all c

ities

: 2.5

% (

2.1,

2.9

) w

est

ern

citie

s: 3

.1%

(2.

3, 3

.8)

cent

ral-e

aste

rn c

ities

: 2.

3%

(1.

7,

2.9)

old

met

hod:

al

l citi

es: 1

.3%

(0.

9, 1

.7)

we

ster

n ci

ties:

2.9

% (

2.1,

3.7

) ce

ntra

l-eas

tern

citi

es:

0.6

% (

0.1,

1.

1).

report no. 4/11

92

Sam

oli

et

al.

(200

3)

(Sam

oli e

t al,

2003

) R

e-an

alys

is

of

abov

e

stud

y.

Re-

anal

ysis

of

ab

ove

stud

y us

ing

strin

gent

co

nver

genc

e cr

iteria

as

wel

l as

natu

ral s

plin

es.

BS

ris

k es

timat

es u

sing

GA

M w

ere

redu

ced

by

~

10%

w

hen

strin

gent

co

nver

genc

e cr

iteria

w

ere

appl

ied.

U

se

of

GLM

/nat

ural

sp

lines

re

sulte

d in

fu

rthe

r an

d gr

eate

r re

duct

ions

.

Res

ults

co

rres

pond

ing

to

abov

e

usin

g th

e

GA

M

with

st

ringe

nt

conv

erge

nce

crite

ria:

all c

ities

: 2.3

% (

1.9,

2.7

)

we

ster

n ci

ties:

2.7

% (

2.0,

3.4

) ce

ntra

l-eas

tern

citi

es:

2.1

% (

1.5,

2.

7).

Cor

resp

ondi

ng

GLM

/nat

ural

sp

lines

res

ults

wer

e:

all c

ities

: 1.2

% (

0.7,

1.7

) w

est

ern

citie

s: 1

.6%

(0.

8, 2

.4)

cent

ral-e

aste

rn c

ities

: 1.

0%

(0.

3,

1.7)

.

Z

miro

u et

al

. (1

998)

(Z

mir

ou e

t al,

1998

) 10

E

urop

ean

citie

s (A

PH

EA

).

1977

-199

2 (s

tudy

ye

ars

diffe

rent

fr

om c

ity to

city

).

Med

ian

BS

leve

ls r

ange

d

from

13

in L

ondo

n to

73

in K

raco

w.

Car

diov

ascu

lar,

re

spira

tory

, an

d di

gest

ive

mor

talit

y se

ries

in 1

0 E

urop

ean

citie

s an

aly

zed

to e

xam

ine

caus

e-sp

ecifi

city

of

air

pol

lutio

n. T

he

mor

talit

y se

ries

wer

e an

alyz

ed f

or a

ssoc

iatio

ns

with

P

M

(BS

, e

xcep

t T

SP

in

M

ilan

an

d B

ratis

lava

; P

M13

in

Lyon

), N

O2,

O3,

an

d S

O2.

P

oiss

on

GL

M

mod

els,

la

g/av

erag

ing

of

pollu

tion,

and

com

puta

tion

of c

ombi

ned

effe

cts

acro

ss t

he c

ities

don

e in

the

sam

e w

ay a

s by

K

atso

uyan

ni

et

al.

(199

7)

(Kat

souy

anni

et

al

, 19

97),

abo

ve.

The

car

diov

ascu

lar

and

resp

irato

ry m

orta

lity

serie

s w

ere

ass

ocia

ted

with

BS

and

SO

2 in

w

est

ern

Eur

opea

n ci

ties,

but

not

in

the

five

cent

ral

Eur

opea

n ci

ties.

NO

2 di

d no

t sh

ow

cons

iste

nt

mor

talit

y as

soci

atio

ns.

RR

s fo

r re

spira

tory

cau

ses

wer

e at

leas

t eq

ual t

o, o

r gr

eate

r th

an

thos

e fo

r ca

rdio

vasc

ula

r ca

uses

. N

o

pollu

tant

ex

hibi

ted

an

y as

soci

atio

n w

ith d

iges

tive

mor

talit

y.

Poo

led

card

iova

scul

ar

mor

talit

y pe

rcen

t e

xce

ss

deat

hs

per

25

µ

g/m

3 inc

reas

e in

BS

for

wes

tern

E

urop

ean

citie

s: 1

.0%

(0.

3,

1.7)

; fo

r re

spira

tory

m

orta

lity,

it

was

2.

0% (

0.8,

3.2

) in

lag

0 (

the

lags

ap

pare

ntly

var

ied

acro

ss c

ities

).

APH

EA 2

Kat

souy

anni

et

al.

(200

1)

(Kat

souy

anni

et a

l, 20

01)

29

Eur

opea

n ci

ties,

19

90-1

997

(var

iabl

e fr

om c

ity to

city

).

Med

ian

PM

10

rang

ed

from

14

(S

tock

holm

) to

66

(P

ragu

e).

Med

ian

BS

ra

nged

fro

m

10

(Dub

lin)

to

64

(Ath

ens)

.

The

2nd

ph

ase

of

AP

HE

A

(AP

HE

A

2)

put

emph

asis

on

th

e ef

fect

m

odifi

catio

n by

ci

ty-

spec

ific

fact

ors.

The

firs

t st

age

of c

ity s

peci

fic

regr

essi

ons

used

G

AM

P

oiss

on

mod

el.

The

se

cond

st

age

re

gres

sion

an

alys

is

was

co

nduc

ted

to e

xpla

in a

ny h

eter

ogen

eity

of

air

pollu

tion

effe

cts

usin

g ci

ty-s

peci

fic

vari

able

s.

The

se c

ity-s

pec

ific

varia

ble

s in

clud

ed a

vera

ge

air

pollu

tion

leve

ls,

ave

rage

te

mpe

ratu

re/h

umid

ity,

age

- st

and

ardi

ze

mor

talit

y ra

te, r

egio

n in

dica

tors

, etc

.

The

aut

hors

fou

nd s

ever

al e

ffect

mod

ifier

s.

The

citi

es w

ith h

ighe

r N

O2 l

evel

s sh

ow

ed

larg

er P

M e

ffec

ts.

The

citi

es w

ith w

arm

er

clim

ate

sho

we

d la

rger

PM

eff

ects

. T

he c

ities

w

ith l

ow

sta

ndar

dize

d m

orta

lity

rate

sho

we

d la

rger

PM

effe

cts.

Tot

al m

orta

lity

exce

ss r

isk

per

50

µg/

m3 in

crea

se in

PM

10:

F

ixed

ef

fect

s m

odel

: 3.

5%

(2.9

, 4.

1) R

ando

m e

ffect

s m

odel

: 3.

1%

(2.1

, 4.2

).

report no. 4/11

93

Kat

souy

anni

et

al.

(200

3)

(Kat

souy

anni

et a

l, 20

03)

Re-

anal

ysis

of

ab

ove

st

udy.

Re-

anal

ysis

of

ab

ove

stud

y us

ing

strin

gent

co

nver

genc

e cr

iteria

as

wel

l as

nat

ural

spl

ines

an

d pe

naliz

ed s

plin

es.

The

po

oled

es

timat

e (r

ando

m

effe

cts

estim

ate)

w

as

redu

ced

by

4%

whe

n st

ringe

nt c

onve

rgen

ce c

riter

ia i

n G

AM

wer

e us

ed,

by

34%

w

hen

natu

ral

splin

es

wer

e us

ed,

and

by 1

1% w

hen

pen

aliz

ed s

plin

es

wer

e u

sed.

T

he

patte

rn

of

effe

ct

mod

ifica

tion

orig

inal

ly

rep

orte

d re

mai

ned

the

sam

e.

The

or

igin

al

findi

ngs

wer

e un

chan

ged.

Tot

al m

orta

lity

exce

ss r

isk

per

50

µg/

m3

incr

ease

in

P

M10

us

ing

G

AM

(s

trin

gent

co

nver

genc

e cr

iteria

): f

ixed

effe

cts:

3.3

% (

2.7,

3.

9)

rand

om

effe

cts:

3.

0%

(2.0

, 4.

1)

GLM

/nat

ural

spl

ines

wer

e

fixed

effe

cts:

2.1

% (

1.5,

2.8

)

rand

om e

ffect

s: 2

.1%

(1.

2, 3

.0)

P

enal

ized

spl

ines

fix

ed e

ffect

s: 2

.9%

(2.

3, 3

.6)

ra

ndom

effe

cts:

2.8

% (

1.8,

3.8

).

Tou

loum

i et

al

. (1

997)

(T

oulo

umi e

t al,

1997

) 6

Eur

opea

n ci

ties

(AP

HE

A).

19

77-1

992

(stu

dy

year

s di

ffere

nt

from

city

to c

ity).

M

edia

n B

S le

vels

ran

ged

fr

om

14.6

in

Lo

ndon

to

84

.4 in

Ath

ens.

Res

ults

of

the

shor

t-te

rm e

ffect

s of

am

bien

t N

O2

and/

or

O3

on

daily

de

aths

fr

om

all

caus

es

(exc

lud

ing

acci

dent

s) w

ere

disc

usse

d to

pro

vide

a

basi

s fo

r co

mpa

rison

with

est

imat

ed S

O2

or

BS

ef

fect

s in

A

PH

EA

ci

ties.

P

oiss

on

G

LM

mod

els,

la

g/av

erag

ing

of

pollu

tion,

a

nd

the

com

puta

tion

of

com

bine

d ef

fect

s ac

ross

th

e ci

ties

wer

e do

ne i

n th

e sa

me

way

as

don

e by

K

atso

uyan

ni

et

al.

(199

7)

(Kat

souy

anni

et

al

, 19

97).

Sig

nific

ant

po

sitiv

e as

soci

atio

ns w

ere

fou

nd

betw

een

daily

dea

ths

and

bot

h N

O2

and

O3.

T

here

wa

s a

tend

ency

for

lar

ger

effe

cts

of

NO

2 in

citi

es w

ith h

ighe

r le

vels

of

BS

. W

hen

BS

w

as

incl

uded

in

th

e m

odel

, po

oled

es

timat

e fo

r O

3 ef

fect

w

as

only

sl

ight

ly

redu

ced,

bu

t co

effic

ient

fo

r N

O2

wa

s re

duce

d by

ha

lf.

Aut

hor

s sp

ecul

ated

th

at

shor

t-te

rm e

ffect

s of

NO

2 on

mor

talit

y w

ere

conf

ound

ed

by

othe

r ve

hicl

e-de

rived

po

lluta

nts.

NO

2 an

d/or

O3 e

stim

ates

onl

y.

Zan

obet

ti et

al

., 20

02

(Zan

obet

ti et

al,

2002

) 19

90-1

996

(var

iabl

e fr

om

city

to

ci

ty).

10

E

urop

ean

citie

s (2

/3

of

popu

latio

n)

from

th

e A

PH

EA

2 s

tud

y.

Mea

n P

M10

ran

ged

from

16

(S

tock

holm

) to

76

(P

ragu

e).

Ana

lysi

s of

m

orta

lity

disp

lace

men

t up

to

40

da

ys.

In T

he f

irst

stag

e co

nsis

ted

of c

ity s

pec

ific

regr

essi

ons

usin

g G

AM

Po

isso

n m

odel

s w

ith 4

th

degr

ee

poly

nom

ial

dist

ribut

ed

lag

cons

trai

nts

with

up

to 4

0 da

ys.

In t

he s

econ

d st

age

the

city

-sp

ecifi

c es

timat

es

wer

e co

mbi

ned

usin

g a

ra

ndom

effe

ct m

odel

.

The

ov

eral

l ef

fect

of

P

M10

for

the

4th

dist

ribut

ed

lag

mod

el

was

hi

gher

(1

.61%

in

crea

se i

n da

ily d

eath

s pe

r 10

µg/

m3 )

than

th

e m

odel

con

side

ring

only

lag

0-1

(0.7

0 %

).

The

re

sults

w

ere

unc

han

ged

whe

n a

n un

cons

trai

ned

di

strib

uted

la

g m

odel

w

as

used

. T

his

sugg

ests

tha

t th

e ef

fect

of

PM

on

mor

talit

y is

not

due

prim

arily

to

shor

t-te

rm

mor

talit

y di

spla

cem

ent.

Fo

r 4th

de

gree

po

lyno

mia

l di

strib

uted

la

g m

odel

, to

tal

mor

talit

y e

xces

s pe

r 50

µ

g/m

3 in

crea

se w

as 8

.1%

(5.

1, 1

1.0)

.

report no. 4/11

94

Zan

obet

ti an

d S

chw

artz

(2

003)

(Z

anob

etti

and

Sch

war

tz, 2

003)

R

e-an

alys

is o

f th

e ab

ove

stud

y.

Re-

anal

ysis

of

ab

ove

stud

y us

ing

strin

gent

co

nver

genc

e cr

iteria

as

wel

l as

nat

ural

spl

ines

an

d pe

naliz

ed s

plin

es.

The

po

oled

P

M10

(la

g 0-

1)

mor

talit

y ris

k es

timat

e w

as r

educ

ed b

y 4%

whe

n st

ringe

nt

conv

erge

nce

crite

ria i

n G

AM

wer

e us

ed,

by

18%

whe

n pe

naliz

ed s

plin

es w

ere

used

. F

or

the

4th

degr

ee

poly

nom

ial

dist

ribut

ed

lag

mod

el,

corr

espo

ndin

g re

duct

ions

wer

e 10

%

and

26%

.

Com

bine

d to

tal

mor

talit

y ex

cess

ris

k pe

r 50

µg/

m3 i

ncre

ase

PM

10

(lag

0-1)

w

as

3.4%

(2

.0,

4.8)

us

ing

GA

M

with

st

ringe

nt

conv

erge

nce

crite

ria.

For

4th

de

gree

po

lyno

mia

l di

strib

uted

lag

mod

el,

it w

as 7

.5%

(4

.4,

10.7

).

Cor

resp

ondi

ng

redu

ctio

ns

usin

g pe

naliz

ed

splin

es w

ere

2.9%

(1.

4, 4

.4)

and

5.6%

(1.

5, 9

.8),

res

pect

ivel

y.

Zan

obet

ti et

al

., 20

03

(Zan

obet

ti et

al,

2003

) 10

citi

es o

f th

e A

PH

EA

2

proj

ect,

1990

-199

6.

PM

10

mea

ns

rang

ing

betw

een

15.5

(S

tock

holm

) an

d 76

.2

(Pra

gue)

.

Thi

s st

udy

anal

ysed

the

acu

te a

nd m

ediu

m-t

erm

(w

eeks

to

mon

ths)

exp

osur

e ef

fect

s of

PM

10 o

n

card

iova

scul

ar a

nd r

espi

rato

ry m

orta

lity,

usi

ng a

m

ulti-

city

hi

erar

chic

al

mod

elin

g ap

proa

ch.

A

GA

M

Poi

sson

re

gres

sion

w

as

fitte

d an

d an

un

cons

trai

ned

dist

ribut

ed l

ag a

nd a

4th d

egre

e po

lyno

mia

l di

strib

uted

lag

wer

e us

ed t

o m

odel

th

e ef

fect

of

PM

10 e

xpos

ure

on d

eath

s up

to

40

days

afte

r th

e ex

posu

re.

The

mod

el w

as a

djus

ted

for

wea

ther

, in

fluen

za

epid

emic

s, h

olid

ays,

and

day

of t

he w

eek.

Thi

s st

udy

conf

irmed

tha

t m

ost

of t

he e

ffect

on

mor

talit

y of

air

pollu

tion

was

not

sim

ply

adva

nced

by

a fe

w w

eeks

and

tha

t ef

fect

s pe

rsis

ted

for

mor

e th

an

1 m

onth

af

ter

expo

sure

. T

he e

ffect

siz

e es

timat

e fo

r P

M10

do

uble

d w

hen

cons

ider

ing

long

er-t

erm

ef

fect

s fo

r al

l de

aths

and

for

car

diov

ascu

lar

deat

hs

and

beca

me

five

times

hi

gher

fo

r re

spira

tory

dea

ths.

The

effe

cts

wer

e si

mila

r w

hen

stra

tifyi

ng b

y ag

e gr

oups

.

Con

side

ring

PM

10 t

he d

ay o

f an

d da

y be

fore

the

dea

th,

the

perc

ent

incr

ease

m

orta

lity

for

an

incr

emen

t of

10

µ

g/m

3 of

P

M10

w

as

0.74

%

(-0.

17,

1.66

) fo

r re

spira

tory

de

aths

an

d 0.

69%

(0

.31,

1.

08)

for

CV

D

deat

hs.

Cor

resp

ondi

ng

estim

ates

in

un

rest

ricte

d di

strib

uted

la

g m

odel

s, w

ere

4.20

% (

1.08

, 7.

42)

and

1.97

%

(1.3

8,

2.55

),

resp

ectiv

ely.

report no. 4/11

95

Aga

et

al.,

2003

(A

ga e

t al

, 200

3)

28

Eur

opea

n ci

ties

AP

HE

A 2

pro

ject

. D

aily

m

ean

P

M10

(2

1

citie

s)

betw

een

15

an

d 66

an

d B

S

(14

citie

s)

betw

een

10 a

nd 6

4.

To

stud

y th

e ef

fect

s of

am

bien

t pa

rtic

le

conc

entr

atio

ns

(BS

and

PM

10)

on t

otal

mor

talit

y

amon

g pe

rson

s ag

ed 6

5 ye

ars

or m

ore,

a 2

-st

age

anal

ysis

w

as

app

lied,

as

sess

ing

city

-sp

ecifi

c ef

fect

s fir

st a

nd t

hen

over

all e

ffect

s w

as

used

afte

r ad

just

men

t fo

r se

ason

ality

, lo

ng-t

erm

tr

ends

, te

mpe

ratu

re,

hum

idity

, in

fluen

za

epid

emic

s,

othe

r un

usua

l ev

ents

, da

y of

th

e w

eek,

and

hol

iday

s. L

ag 0

-1 w

as

a p

riori

cho

sen

as e

xpos

ure

mea

sure

.

A s

igni

fican

t as

soci

atio

n w

ith t

otal

mor

talit

y w

as

foun

d fo

r bo

th P

M10

and

BS

am

ong

the

elde

rly,

with

re

lativ

e ris

ks

com

para

ble

or

slig

htly

hig

her

than

tho

se o

bser

ved

for

tota

l m

orta

lity

and

sim

ilar

effe

ct

mod

ifica

tion

patte

rns.

Per

cent

ex

cess

m

orta

lity

for

incr

ease

by

10 µ

g/m

3 of

PM

10 (

lag

0-1)

T

otal

pop

ulat

ion

Fix

ed e

ffect

s:

0.71

% (

0.60

, 0.

83)

R

ando

m

effe

cts:

0.67

%

(0.4

7,

0.87

) E

lder

ly (

65+

) F

ixed

effe

cts:

0.

79%

(0.

66,

0.92

)

Ran

dom

ef

fect

s:

0.

74%

(0

.52,

0.

95)

Per

cent

ex

cess

m

orta

lity

for

incr

ease

by

10

µg/

m3 o

f B

S (

lag

0-

1)

Tot

al p

opul

atio

n F

ixed

effe

cts:

0.

51%

(0.

39,

0.64

)

Ran

dom

ef

fect

s:

0.

58%

(0

.32,

0.

84)

Eld

erly

(65

+)

Fix

ed e

ffect

s:

0.63

% (

0.49

, 0.

78)

R

ando

m

effe

cts:

0.68

%

(0.4

3,

0.92

).

Ana

litis

et

al

., 20

06

(Ana

litis

et a

l, 20

06)

29

Eur

opea

n ci

ties

AP

HE

A2

proj

ect

. M

ean

PM

10

(21

citie

s)

betw

een

9 a

nd

64

and

BS

(1

5 ci

ties)

be

twee

n

14 a

nd 1

66.

To

stud

y th

e ef

fect

s of

am

bien

t pa

rtic

le

conc

entr

atio

ns

(BS

and

PM

10)

on c

ardi

ova

scul

ar

and

resp

irato

ry m

orta

lity,

a 2

-sta

ge h

iera

rchi

cal

mod

elin

g ap

proa

ch

asse

ssin

g ci

ty-s

pec

ific

effe

cts

first

and

the

n ov

eral

l ef

fect

s w

as

used

af

ter

adju

stm

ent

for

seas

onal

ity,

long

-ter

m

tren

ds,

tem

pera

ture

, hu

mid

ity,

influ

enza

ep

idem

ics,

ot

her

unus

ual

even

ts,

day

of

the

wee

k, a

nd h

olid

ays.

Fur

ther

adj

ustm

ent

for

the

daily

leve

ls o

f ot

her

pollu

tant

s w

as p

erfo

rmed

in

2-po

lluta

nt m

odel

s.

A s

ign

ifica

nt e

xce

ss r

isk

wa

s fo

und

for

both

P

M10

and

BS

. T

he g

reat

est

rela

tive

effe

ct

mod

ifica

tion

for

PM

10

on

CV

D

mor

talit

y ca

me

from

m

ean

tem

pera

ture

an

d ci

ty-

aver

age

NO

2 c

once

ntra

tion

s. W

arm

er t

ow

ns

with

mor

e N

O2

sho

wed

larg

er e

ffec

ts.

The

re

wa

s le

ss e

ffect

mod

ifica

tion

by N

O2

for

BS

th

an f

or P

M10

, su

gges

ting

diffe

rent

ial e

ffect

s of

tra

ffic

part

icle

s, f

or w

hich

PM

10 i

s a

less

go

od in

dica

tor

than

BS

.

An

incr

emen

t in

PM

10 o

f 10

µg/

m3

(lag

0-1)

w

as

asso

ciat

ed

with

in

crea

ses

of 0

.76%

(0.

47,

1.05

) in

C

VD

de

aths

an

d 0.

58%

(0

.21,

0.

95)

in

resp

irato

ry

deat

hs.

The

sa

me

incr

emen

t in

B

S

was

as

soci

ated

w

ith

incr

ease

s of

0.

62%

(0

.35,

0.

90)

and

0.84

%

(0.1

1, 1

.57)

, res

pect

ivel

y.

report no. 4/11

96

Tou

loum

i et

al

20

05

(Tou

loum

i et a

l, 20

05)

7 E

urop

ean

citie

s A

PH

EA

-2 p

roje

ct,

1990

-19

97.

Med

ian

PM

10

rang

ing

betw

een

13.7

and

40.

2.

To

inve

stig

ate

the

effe

ct o

f in

fluen

za e

pid

emic

s on

the

ass

ocia

tion

betw

een

PM

10 a

nd t

otal

and

ca

rdio

vasc

ular

m

orta

lity,

a

GA

M

Po

isso

n re

gres

sion

afte

r ad

just

men

t fo

r da

y of

wee

k an

d ho

liday

s w

as

used

. T

o co

ntro

l fo

r in

fluen

za

epid

emic

s, 1

0 m

etho

ds w

ere

com

pare

d.

The

si

gnifi

cant

an

d di

rect

as

soci

atio

n be

twee

n P

M10

and

dai

ly n

um

ber

of d

eath

s re

mai

ned

and

even

in

crea

sed

afte

r co

ntro

lling

for

inf

luen

za,

rega

rdle

ss o

f th

e m

etho

d us

ed f

or c

ontr

ol.

Sim

ple

met

hods

, su

ch a

s 1

or m

ultip

le in

dica

tors

for

influ

enza

ep

idem

ics,

are

rel

ativ

ely

easy

and

effe

ctiv

e w

ays

to

co

ntro

l or

to

ev

alua

te

pote

ntia

l co

nfou

ndin

g ef

fect

of

influ

enza

epi

dem

ics.

R

espi

rato

ry

mor

talit

y da

ta

may

be

us

ed

inst

ead

of i

nflu

enza

cas

es d

ata

if th

e la

tter

ar

e no

t av

aila

ble;

res

pira

tory

mor

talit

y da

ta

may

be

m

ore

appr

opria

te

way

to

co

ntro

l w

hen

the

outc

ome

stud

ied

is

a

mor

talit

y ou

tcom

e. N

one

of t

he m

eth

ods

inve

stig

ated

in

th

is

stu

dy

sugg

este

d ap

prec

iabl

e co

nfou

ndin

g b

y in

fluen

za e

pide

mic

s.

An

incr

emen

t b

y 10

µg/

m3 (

lag

0-1)

in

P

M10

co

ncen

trat

ion

s w

as

asso

ciat

ed

with

a

0.48

%

(0.2

7,

0.70

) in

crea

se

in

daily

m

orta

lity

with

out

adju

stm

ent

for

influ

enza

ep

idem

ics,

a

nd

rang

ed

betw

een

0.

45%

(0

.26,

0.

69)

to

0.67

%

(0.4

6,

0.89

),

afte

r di

ffere

nt

adju

stm

ent

for

influ

enza

ep

idem

ics.

T

he

corr

espo

ndin

g

figur

es

for

CV

D

mor

talit

y w

ere

0.85

%

(0.5

3,

1.18

) w

itho

ut

the

m

etho

ds

of

cont

rol

and

from

0.

86%

(0

.53,

1.

19)

to

1.06

%

(0.7

4, 1

.39)

with

the

met

hod

s of

co

ntro

l.

Nat

iona

l stu

dies

THE

NET

HER

LAN

DS

H

oek

et a

l. (2

000)

(H

oek

et a

l, 20

00)

The

N

ethe

rland

s,

1986

-19

94.

PM

10 m

edia

n: 3

4 B

S m

edia

n: 1

0.

Tot

al,

card

iova

scul

ar,

CO

PD

, an

d pn

eum

onia

m

orta

lity

serie

s w

ere

regr

esse

d on

PM

10,

BS

, su

lfate

, ni

trat

e,

O3,

S

O2,

C

O,

adju

stin

g fo

r se

ason

al

cycl

es,

day

of

wee

k,

influ

enza

, te

mpe

ratu

re,

and

hum

idity

usi

ng P

oiss

on G

AM

m

odel

. D

eath

s oc

curr

ing

insi

de

and

out

side

ho

spita

ls w

ere

als

o e

xam

ine

d.

Par

ticul

ate

air

pollu

tion

w

as

less

co

nsis

tent

ly a

ssoc

iate

d w

ith m

orta

lity

than

w

ere

the

gase

ous

pollu

tant

s S

O2

an

d N

O2.

S

ulfa

te,

nitr

ate,

an

d B

S

wer

e m

ore

cons

iste

ntly

ass

ocia

ted

with

tot

al m

orta

lity

than

was

PM

10.

The

RR

s fo

r al

l po

lluta

nts

w

ere

lar

ger

in t

he s

umm

er m

onth

s th

an i

n th

e w

inte

r m

onth

s.

Mor

talit

y e

xce

ss r

isk

est

ima

te p

er

50 µ

g/m

3 PM

10

(lag

0-6)

: 1.

2% (

0.2,

2.2

) fo

r to

tal m

orta

lity

0.

9% (

-0.8

, 2.7

) fo

r C

VD

5.

9% (

0.9,

11.

2) fo

r C

OP

D

10.1

% (

3.6,

17.

1) fo

r pn

eum

onia

.

Hoe

k (2

003)

(H

oek,

20

03)

Re-

anal

ysis

of

the

abov

e

stud

y.

Re-

anal

ysis

of

ab

ove

stud

y us

ing

strin

gent

co

nver

genc

e cr

iteria

and

nat

ural

spl

ines

. V

ery

little

ch

ange

in

P

M

risk

coef

ficie

nts

(o

ften

slig

htly

inc

reas

ed)

wh

ethe

r G

AM

with

st

ringe

nt

conv

erge

nce

crite

ria

or

GLM

/nat

ural

spl

ines

wer

e us

ed.

Est

imat

es p

er 5

0 µ

g/m

3 PM

10 (

lag

0-

6)

usin

g G

AM

w

ith

strin

gent

co

nver

genc

e cr

iteria

: T

otal

mor

talit

y: 1

.4%

(0.

3, 2

.6)

CV

D: 0

.9%

(-0

.8, 2

.7)

CO

PD

: 6.

1% (

1.0,

11.

4)

Pne

umon

ia: 1

0.3%

(3.

7, 1

7.2)

U

sing

GLM

/na

tura

l spl

ines

wer

e:

Tot

al m

orta

lity:

1.2

% (

-0.1

, 2.5

) C

VD

: 1.6

% (

-0.3

, 3.5

) C

OP

D:

6.0%

(0.

4, 1

1.8)

P

neum

onia

: 10.

7% (

3.5,

18.

3).

report no. 4/11

97

Hoe

k et

al.

(200

1) (

Hoe

k et

al,

2001

) T

he

Net

herla

nds.

19

86-

1994

. P

M10

med

ian:

34

BS

med

ian:

10.

Thi

s st

udy

of

the

who

le

popu

latio

n of

th

e N

ethe

rland

s, w

ith i

ts l

arge

sam

ple

size

(m

ean

daily

tot

al d

eath

s ~

330

), a

llow

ed e

xam

inat

ion

of

spec

ific

card

iova

scul

ar c

ause

of

deat

hs.

GA

M

Poi

sson

re

gre

ssio

n m

odel

s,

adju

stin

g fo

r se

ason

al c

ycle

s, t

empe

ratu

re,

hum

idity

, an

d da

y of

we

ek w

ere

used

.

Dea

ths

due

to

hear

t fa

ilure

, ar

rhyt

hmia

, ce

rebr

ovas

cula

r ca

uses

, an

d th

rom

bocy

tic

caus

es w

ere

mor

e st

rong

ly (

~ 2

.5 t

o 4

times

la

rger

re

lativ

e ris

ks)

asso

ciat

ed

with

ai

r po

llutio

n th

an

the

over

all

CV

D

deat

hs

or

AM

I and

oth

er IH

D d

eath

s.

Fo

r P

M10

(la

g 0-

6),

mor

talit

y pe

r 50

µg/

m3 in

cre

ase:

T

otal

CV

D: 0

.9%

(-0

.8, 2

.7)

AM

I/IH

D: 0

.3%

(-2

.3, 3

.0)

Arr

hyth

mia

2.5

% (

- 4.

3, 9

.9)

Hea

rt fa

ilure

2.2

% (

-2.5

, 7.2

) C

ereb

rova

scul

ar 1

.9%

(-1

.8, 5

.8)

Thr

ombo

cytic

: 0.6

% (

-6.8

, 8.7

).

The

ex

cess

ris

ks

for

BS

w

ere

la

rger

and

mor

e si

gnifi

cant

tha

n th

ose

for

PM

10.

Hoe

k (2

003)

(H

oek,

20

03)

Re-

anal

ysis

of

the

abov

e

stud

y.

Re-

anal

ysis

of

ab

ove

stud

y us

ing

strin

gent

co

nver

genc

e cr

iteria

and

nat

ural

spl

ines

. V

ery

little

ch

ange

in

P

M

risk

coef

ficie

nts

(o

ften

slig

htly

inc

reas

ed)

wh

ethe

r G

AM

with

st

ringe

nt

conv

erge

nce

crite

ria

or

GLM

/nat

ural

spl

ines

wer

e us

ed.

Fo

r P

M10

(la

g 0-

6),

perc

ent

exce

ss r

isk

mor

talit

y pe

r 50

µg/

m3

incr

ease

u

sing

G

AM

w

ith

strin

gent

co

nver

genc

e cr

iteria

w

ere:

T

otal

CV

D: 0

.9%

(-0

.8, 2

.7),

A

MI/I

HD

: 0.4

% (

-2.2

, 3.0

),

Arr

hyth

mia

: 2.7

% (

- 4.

2, 1

0.1)

, H

eart

failu

re: 2

.4%

(-2

.3, 7

.4),

C

ereb

rova

scul

ar: 2

.0%

(-1

.7, 5

.9),

T

hrom

bocy

tic: 0

.7 %

(-6.

8, 8

.8).

T

he R

Rs

for

BS

wer

e la

rger

and

m

ore

sign

ifica

nt

than

th

ose

fo

r P

M10

.

report no. 4/11

98

Fis

cher

et

al

. (2

003)

(F

isch

er e

t al,

2003

) T

he

Net

herla

nds.

19

86-

1994

. P

M10

med

ian:

34

BS

med

ian:

10.

Age

-spe

cific

ana

lysi

s of

the

pre

viou

s st

udy.

The

re

latio

nshi

p b

etw

een

da

ily

(tot

al

and

caus

e-sp

ecifi

c) m

orta

lity

and

air

pollu

tion

(PM

10,

BS

an

d ot

her

co-p

ollu

tant

s, i

nclu

ding

O3,

SO

2, C

O

and

NO

2)

wa

s m

odel

led

usin

g P

oiss

on

regr

essi

on

anal

ysis

. A

ll po

llutio

n m

orta

lity

asso

ciat

ions

wer

e ad

just

ed f

or lo

ng-t

erm

tre

nds,

se

ason

al t

ren

ds,

influ

enza

epi

dem

ics,

am

bien

t te

mpe

ratu

re,

ambi

ent

rela

tive

hum

idity

, da

y of

th

e w

eek

and

holid

ays,

usi

ng

GA

M m

odel

s. T

he

wee

kly

aver

age

conc

entr

atio

n fo

r ot

her

pollu

tant

s (la

g 0

-6)

was

use

d fo

r P

M10

and

BS

.

PM

10 s

light

ly i

ncre

ased

tot

al m

orta

lity,

and

ca

rdio

vasc

ular

mor

talit

y in

the

eld

erly

onl

y (s

ubje

cts

age

d 65

yea

rs o

r m

ore)

. B

oth

BS

an

d P

M10

si

gni

fican

tly

incr

ease

d m

orta

lity

for

pneu

mon

ia i

n th

e el

derly

, on

ly.

Sim

ilar

incr

ease

d ris

ks

wer

e sh

ow

n fo

r th

e ot

her

cons

ider

ed c

o-p

ollu

tant

s.

Per

cent

exc

ess

tota

l m

orta

lity

risk

per

100

µg/

m3 in

crea

se o

f PM

10:

2% (

0, 3

) P

erce

nt

exce

ss

for

80

µg/

m3

incr

ease

of

P

M10

(9

9th-1

st

perc

entil

e):

Car

diov

ascu

lar

mor

talit

y (y

ears

):

<45

: -9.

4 (-

27.2

, 12.

8)

45-6

4: 2

.3 (

-5.5

, 10.

6)

65-7

4: 0

.2 (

-5.5

, 6.2

) 75

+: 1

.6 (

-1.9

, 5.2

) C

OP

D m

orta

lity

(yea

rs):

<

45: 1

5.3

(-41

.3, 1

26.8

) 45

-64:

13.

9 (-

16.1

, 54.

1)

65-7

4: 1

6.6

(-0.

9, 3

7.2)

75

+: 6

.6 (

-3.5

, 17.

8)

Pne

umon

ia m

orta

lity

(yea

rs):

<

45: 4

2.7

(-19

.4, 1

52.5

) 45

-64:

71.

2 (4

.2, 1

81.5

) 65

-74:

24.

0 (-

12.1

, 74.

8)

75+

: 12.

3 (1

.1, 2

4.7)

P

erce

nt

exce

ss

for

40

µg/

m3

incr

ease

of

B

S

(99

th-1

st

perc

entil

e):

Car

diov

ascu

lar

mor

talit

y (y

ears

):

<45

: 5.7

(-6

.4, 1

9.6)

45

-64:

0.0

(-4

.3, 4

.6)

65-7

4: 4

.0 (

0.6,

7.5

) 75

+: 3

.0 (

1.0,

5.1

) C

OP

D m

orta

lity

(yea

rs):

<

45: -

12.8

(-4

0.1,

27.

0)

45-6

4: 2

.5 (

-13.

0, 2

0.9)

65

-74:

20.

4 (9

.5, 3

2.4)

75

+: 1

.2 (

-4.3

, 7.0

) P

neum

onia

mor

talit

y (y

ears

):

<45

:-25

.9 (

-48.

1, 5

.7)

45-6

4: 2

6.4

(-6.

6, 7

1.1)

65

-74:

-4.

9 (-

23.3

, 17.

9)

75+

: 12.

3 (5

.5, 1

9.6)

.

report no. 4/11

99

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Bre

mne

r et

al

. (1

999)

(B

rem

ner

et a

l, 19

99)

Lond

on,

UK

, 19

92-1

994.

B

S m

ean:

13

P

M10

mea

n: 2

9.

Tot

al,

card

iova

scul

ar,

and

resp

irato

ry (

by a

ge)

mor

talit

y se

ries

wer

e re

gres

sed

on P

M10

, B

S,

O3,

NO

2, C

O,

and

SO

2, a

djus

ting

for

sea

sona

l cy

cles

, da

y of

w

eek,

in

fluen

za,

holid

ays,

te

mpe

ratu

re,

hum

idity

, an

d au

toco

rrel

atio

n us

ing

Poi

sson

GLM

mod

el.

All

effe

ct s

ize

est

imat

es (

exc

ept

O3)

we

re

posi

tive

for

tota

l de

aths

(t

houg

h no

t si

gnifi

cant

fo

r si

ngle

la

g m

odel

s).

The

ef

fect

s of

O3

foun

d in

198

7-19

92 w

ere

not

re

plic

ated

, ex

cept

in

card

iova

scul

ar d

eath

s.

Mul

tiple

day

ave

ragi

ng (

e.g.

, 0-

1, 0

-2 d

ays)

te

nded

to

give

mor

e si

gnifi

cant

effe

ct s

ize

estim

ates

. T

he e

ffect

siz

e fo

r P

M10

and

BS

w

ere

sim

ilar

for

the

sam

e di

strib

utio

nal

incr

emen

t.

Per

cent

e

xce

ss

risk

1.9%

(0

.0,

3.8)

per

25

µg/

m3 B

S a

t la

g 1;

1.

3%

(-1.

0,

3.6)

pe

r 50

µ

g/m

3 P

M10

at l

ag 1

for

tota

l dea

ths.

R

espi

rato

ry d

eath

s (la

g 3)

: 4.

9%

(0.5

, 9.4

).

CV

D

deat

hs

(lag

1):

3.0%

(0

.3,

5.7)

.

Pre

scot

t et

al

. (1

998)

(P

resc

ott e

t al,

1998

) E

dinb

urgh

, U

K,

1981

-19

95.

PM

10

mea

n:

21,

by

TE

OM

on

ly

for

1992

-19

95;

BS

mea

n: 8

.7.

Bot

h m

orta

lity

(tot

al,

card

iova

scul

ar,

and

resp

irato

ry)

and

emer

genc

y ho

spita

l adm

issi

ons

(car

diov

ascu

lar

and

resp

irato

ry),

in

tw

o ag

e gr

oups

(<

65 a

nd ≥

65

year

s),

wer

e an

alyz

ed f

or

thei

r as

soci

atio

ns w

ith P

M10

, B

S,

SO

2, N

O2,

O3,

an

d C

O,

usi

ng

Po

isso

n

GLM

re

gres

sion

ad

just

ing

for

seas

onal

cy

cles

, da

y-of

-wee

k,

tem

pera

ture

, and

win

d sp

eed.

Am

ong

all

the

pollu

tant

s,

BS

w

as

mos

t si

gnifi

cant

ly

asso

ciat

ed

with

al

l ca

use

, ca

rdio

vasc

ular

, an

d re

spira

tory

m

orta

lity

serie

s.

In

the

su

bset

in

w

hich

P

M10

d

ata

w

ere

av

aila

ble,

th

e R

R

est

imat

es

for

BS

an

d P

M10

for

all

caus

e el

derly

mor

talit

y w

ere

com

para

ble.

O

ther

po

lluta

nts’

m

orta

lity

asso

ciat

ions

wer

e ge

nera

lly in

cons

iste

nt.

Per

cent

e

xce

ss

risk

3.8%

(1

.3,

6.4)

per

25

µg/

m3 i

ncre

ase

in B

S

for

all

caus

e m

orta

lity

in a

ge

65+

gr

oup,

lag

1-3.

Roo

ney

et

al.

(199

8)

(Roo

ney

et a

l, 19

98)

Eng

land

and

Wal

es,

and

G

reat

er L

ondo

n, U

K

PM

10

mea

n:

56

(dur

ing

the

wor

st h

eat

wa

ve);

P

M10

m

ean:

39

(J

uly-

Aug

ust)

.

Exc

ess

deat

hs,

by

age,

sex

, an

d ca

use,

dur

ing

the

1995

hea

t w

ave

wer

e es

timat

ed b

y ta

king

th

e di

ffere

nce

bet

wee

n th

e d

eath

s du

ring

heat

w

ave

an

d th

e 31

-day

m

ovin

g av

erag

es

(for

19

95 a

nd 1

993-

1994

sep

arat

ely)

. T

he p

ollu

tion

effe

cts,

add

itive

ly f

or O

3, P

M10

, an

d N

O2,

wer

e es

timat

ed

base

d on

th

e

publ

ishe

d se

ason

-sp

ecifi

c co

effic

ient

s fr

om t

he 1

987-

199

2 st

udy

(And

erso

n et

al.,

199

6) (

An

ders

on e

t al,

1996

).

Air

pollu

tion

leve

ls a

t al

l th

e lo

catio

ns r

ose

durin

g th

e h

eat

wav

e.

8.9%

an

d

16.1

%

exce

ss d

eath

s w

ere

estim

ated

for

Eng

land

an

d W

ales

, an

d G

reat

er

Lond

on,

resp

ectiv

ely.

Of

thes

e ex

cess

dea

ths,

up

to

62%

an

d

38%

, re

spec

tivel

y fo

r th

ese

lo

catio

ns,

ma

y be

attr

ibut

abl

e to

com

bin

ed

pollu

tion

effe

cts.

2.6%

incr

ease

for

PM

10 in

Gre

ater

Lo

ndon

dur

ing

hea

t w

ave.

Wor

dley

et

al

. (1

997)

(W

ordl

ey e

t al,

1997

) B

irmin

gham

, U

K,

1992

-19

94.

PM

10 m

ean:

26.

Mor

talit

y da

ta

wer

e an

alyz

ed

for

CO

PD

, pn

eum

onia

, al

l re

spira

tory

di

seas

es,

all

circ

ulat

ory

dise

ases

, an

d a

ll ca

uses

. M

ort

ality

as

soci

atio

ns w

ith P

M10

, N

O2,

SO

2, a

nd O

3 w

ere

exam

ine

d u

sing

O

LS

(w

ith

som

e he

alth

ou

tcom

es

log-

or

sq

uare

-roo

t tr

ansf

orm

ed),

ad

just

ing

for

day-

of-w

eek,

mon

th,

linea

r tr

end,

te

mpe

ratu

re

and

rela

tive

hum

idity

. T

he

stud

y al

so a

naly

zed

hosp

ital a

dmis

sion

dat

a.

Tot

al,

circ

ulat

ory,

and

CO

PD

dea

ths

wer

e si

gnifi

cant

ly a

ssoc

iate

d w

ith 1

-day

lag

PM

10.

The

ga

seou

s po

lluta

nts

“did

no

t ha

ve

sign

ifica

nt

ass

ocia

tions

in

depe

nden

t fr

om

that

of

PM

10”,

and

the

res

ults

for

gas

eou

s po

lluta

nts

wer

e no

t pr

esen

ted.

The

im

pact

of

red

ucin

g P

M10

to

belo

w 7

0 µ

g/m

3 was

es

timat

ed

to

be

“sm

all”

(0.2

%

for

tota

l de

aths

), b

ut t

he P

M10

lev

el a

bove

70

µg/

m3

occu

rred

onl

y on

ce d

urin

g th

e st

udy

perio

d.

5.6%

(0

.5,

11.0

) pe

r 50

µ

g/m

3 P

M10

at

1 d

lag

for

tot

al d

eath

s.

CO

PD

(1

da

y la

g)

deat

hs:

27.6

(5

.1,

54.9

). C

ircul

ator

y (1

day

lag)

de

aths

: 8.8

(1.

9, 1

7.1)

.

report no. 4/11

100

And

erso

n et

al

. (1

996)

(A

nder

son

et a

l, 19

96)

Lond

on, U

K, 1

987-

1992

. B

S m

ean

15.

Tot

al,

card

iova

scul

ar,

and

resp

irato

ry m

orta

lity

serie

s w

ere

regr

esse

d on

B

S,

O3,

N

O2,

an

d S

O2,

ad

just

ing

for

sea

sona

l cyc

les,

da

y of

wee

k,

influ

enza

, ho

liday

s, t

empe

ratu

re,

hum

idity

, an

d au

toco

rrel

atio

n us

ing

Poi

sson

GLM

mod

el.

Bot

h O

3 (la

g 0)

an

d B

S

(lag

1)

we

re

sign

ifica

nt p

redi

ctor

s of

tot

al d

eath

s. O

3 w

as

also

pos

itive

ly s

igni

fican

tly a

ssoc

iate

d w

ith

resp

irato

ry a

nd c

ardi

ovas

cula

r de

aths

. T

he

effe

ct

size

es

timat

es

per

the

sam

e di

strib

utio

nal

incr

emen

t (1

0% t

o 90

%)

wer

e la

rger

fo

r O

3

than

fo

r B

S.

The

se

effe

cts

wer

e la

rger

in

war

m s

easo

n. S

O2

an

d N

O2

wer

e

not

cons

iste

ntly

a

ssoc

iate

d w

ith

mor

talit

y.

Per

cent

e

xce

ss

mor

talit

y 2.

8%

(1.4

, 4.

3) p

er 2

5 µ

g/m

3 BS

at

1-d

lag

for

tota

l dea

ths.

C

VD

(1

d): 1

.0%

(-1

.1, 3

.1).

R

espi

rato

ry

(1

d):

1.1%

(-

2.7,

5.

0).

And

erso

n et

al

. (2

001)

(A

nder

son

et a

l, 20

01)

The

W

est

Mid

land

s co

nurb

atio

n,

UK

. 19

94-

1996

. P

M m

eans

: P

M10

: 23

, P

M2.

5: 1

5, P

M10

-2.5:

9,

BS

: 13.

2.

Non

-acc

iden

tal

caus

e,

card

iova

scul

ar,

and

resp

irato

ry

mor

talit

y (a

s w

ell

as

hosp

ital

adm

issi

ons)

w

ere

ana

lyze

d fo

r th

eir

asso

ciat

ions

w

ith

PM

in

dic

es

and

gase

ous

pollu

tant

s us

ing

GA

M P

oiss

on m

odel

s ad

just

ing

for

seas

onal

cyc

les,

day

of

wee

k, a

nd w

eat

her.

Dai

ly

non-

acci

dent

al

mor

talit

y w

as

not

as

soci

ated

w

ith

PM

in

dice

s or

ga

seou

s po

lluta

nts

in t

he a

ll-ye

ar a

nal

ysis

. H

ow

ever

, al

l th

e P

M i

ndic

es (

exc

ept

coar

se p

artic

les)

w

ere

posi

tivel

y an

d si

gnifi

cant

ly a

ssoc

iate

d w

ith n

on-a

ccid

enta

l m

orta

lity

(age

ove

r 65

) in

the

war

m s

easo

n. O

f ga

seou

s po

lluta

nts,

N

O2

and

O3

wer

e po

sitiv

ely

and

sign

ifica

ntly

as

soci

ated

with

non

-acc

ide

ntal

mor

talit

y in

w

arm

sea

son

. T

wo

pollu

tant

mod

els

we

re

not

cons

ider

ed

beca

use

“so

few

as

soci

atio

ns w

ere

foun

d”.

Per

cent

exc

ess

mor

talit

y fo

r P

M10

, P

M2.

5, a

nd P

M10

-2.5 (

lag

0-1)

wer

e:

0.2%

(-1

.8,

2.2

) pe

r 24

.4

µg/

m3

PM

10,

0.6%

(-

1.5,

2.

7)

per

17.7

µ

g/m

3 PM

2.5,

and

-0.

6% (

-4.2

, 2.

3)

per

11.3

µg/

m3 P

M10

-2.5 i

n al

l-yea

r an

alys

is.

The

re

sults

fo

r se

ason

sp

ecifi

c an

alys

is

wer

e gi

ven

only

as

fig

ures

.

Kea

tinge

and

Don

alds

on

(200

1)

(Kea

tinge

an

dDon

alds

on, 2

001)

G

reat

er

Lond

on,

Eng

land

, 197

6-1

995.

B

S m

ean:

17.

7.

The

st

udy

exam

ine

d po

tent

ial

conf

oun

ding

ef

fect

s of

at

ypic

al

cold

w

eat

her

on

air

pollu

tion/

mor

talit

y re

latio

nshi

ps.

Firs

t, ai

r po

llutio

n va

riabl

es

(SO

2,

CO

an

d B

S)

wer

e m

odel

ed

as

a fu

nctio

n of

la

gged

w

eath

er

varia

bles

. T

hese

var

iabl

es w

ere

dese

ason

aliz

ed

by r

egre

ssin

g o

n se

ine

and

cosi

ne v

aria

bles

. M

orta

lity

regr

essi

on

(OLS

) in

clud

ed

vario

us

lagg

ed

and

aver

aged

w

eat

her

and

pollu

tion

varia

bles

. A

naly

ses

wer

e co

nduc

ted

in th

e li

near

ra

nge

of m

orta

lity/

tem

pera

ture

rel

atio

nshi

p (1

5 to

0 d

egre

es C

).

Pol

lute

d da

ys w

ere

foun

d to

be

cold

er a

nd

less

w

indy

a

nd

rain

y th

an

usua

l. In

th

e re

gres

sion

of

m

orta

lity

on

the

mul

tiple

-la

gged

te

mpe

ratu

re,

win

d,

rain

, hu

mid

ity,

suns

hine

, S

O2,

C

O,

and

B

S,

cold

te

mpe

ratu

re w

as

asso

ciat

ed w

ith m

orta

lity

incr

ease

, bu

t no

t S

O2

or C

O.

BS

sho

we

d su

gges

tive

evid

ence

, th

ough

not

sta

tistic

ally

si

gnifi

cant

, of

asso

ciat

ion

at la

g 0

and

lag

1.

Per

cent

exc

ess

mor

talit

y 3%

(N

S)

incr

ease

in

da

ily

mor

talit

y pe

r 17

.7 µ

g/m

3 of

BS

(la

g 0

and

1).

report no. 4/11

101

And

erso

n et

al

. (1

996)

(A

nder

son

et a

l, 19

96)

Lond

on, U

K, 1

987-

1992

. B

S m

ean

15.

Tot

al,

card

iova

scul

ar,

and

resp

irato

ry m

orta

lity

serie

s w

ere

regr

esse

d on

B

S,

O3,

N

O2,

an

d S

O2,

ad

just

ing

for

sea

sona

l cyc

les,

da

y of

wee

k,

influ

enza

, ho

liday

s, t

empe

ratu

re,

hum

idity

, an

d au

toco

rrel

atio

n us

ing

Poi

sson

GLM

mod

el.

Bot

h O

3 (la

g 0)

an

d B

S

(lag

1)

we

re

sign

ifica

nt p

redi

ctor

s of

tot

al d

eath

s. O

3 w

as

also

pos

itive

ly s

igni

fican

tly a

ssoc

iate

d w

ith

resp

irato

ry a

nd c

ardi

ovas

cula

r de

aths

. T

he

effe

ct

size

es

timat

es

per

the

sam

e di

strib

utio

nal

incr

emen

t (1

0% t

o 90

%)

wer

e la

rger

fo

r O

3

than

fo

r B

S.

The

se

effe

cts

wer

e la

rger

in

war

m s

easo

n. S

O2

an

d N

O2

wer

e

not

cons

iste

ntly

a

ssoc

iate

d w

ith

mor

talit

y.

Per

cent

e

xce

ss

mor

talit

y 2.

8%

(1.4

, 4.

3) p

er 2

5 µ

g/m

3 BS

at

1-d

lag

for

tota

l dea

ths.

C

VD

(1

d): 1

.0%

(-1

.1, 3

.1).

R

espi

rato

ry

(1

d):

1.1%

(-

2.7,

5.

0).

And

erso

n et

al

. (2

001)

(A

nder

son

et a

l, 20

01)

The

W

est

Mid

land

s co

nurb

atio

n,

UK

. 19

94-

1996

. P

M m

eans

: P

M10

: 23

, P

M2.

5: 1

5, P

M10

-2.5:

9,

BS

: 13.

2.

Non

-acc

iden

tal

caus

e,

card

iova

scul

ar,

and

resp

irato

ry

mor

talit

y (a

s w

ell

as

hosp

ital

adm

issi

ons)

w

ere

ana

lyze

d fo

r th

eir

asso

ciat

ions

w

ith

PM

in

dic

es

and

gase

ous

pollu

tant

s us

ing

GA

M P

oiss

on m

odel

s ad

just

ing

for

seas

onal

cyc

les,

day

of

wee

k, a

nd w

eat

her.

Dai

ly

non-

acci

dent

al

mor

talit

y w

as

not

as

soci

ated

w

ith

PM

in

dice

s or

ga

seou

s po

lluta

nts

in t

he a

ll-ye

ar a

nal

ysis

. H

ow

ever

, al

l th

e P

M i

ndic

es (

exc

ept

coar

se p

artic

les)

w

ere

posi

tivel

y an

d si

gnifi

cant

ly a

ssoc

iate

d w

ith n

on-a

ccid

enta

l m

orta

lity

(age

ove

r 65

) in

the

war

m s

easo

n. O

f ga

seou

s po

lluta

nts,

N

O2

and

O3

wer

e po

sitiv

ely

and

sign

ifica

ntly

as

soci

ated

with

non

-acc

ide

ntal

mor

talit

y in

w

arm

sea

son

. T

wo

pollu

tant

mod

els

we

re

not

cons

ider

ed

beca

use

“so

few

as

soci

atio

ns w

ere

foun

d”.

Per

cent

exc

ess

mor

talit

y fo

r P

M10

, P

M2.

5, a

nd P

M10

-2.5 (

lag

0-1)

wer

e:

0.2%

(-1

.8,

2.2

) pe

r 24

.4

µg/

m3

PM

10,

0.6%

(-

1.5,

2.

7)

per

17.7

µ

g/m

3 PM

2.5,

and

-0.

6% (

-4.2

, 2.

3)

per

11.3

µg/

m3 P

M10

-2.5 i

n al

l-yea

r an

alys

is.

The

re

sults

fo

r se

ason

sp

ecifi

c an

alys

is

wer

e gi

ven

only

as

fig

ures

.

Kea

tinge

and

Don

alds

on

(200

1)

(Kea

tinge

an

dDon

alds

on, 2

001)

G

reat

er

Lond

on,

Eng

land

, 197

6-1

995.

B

S m

ean:

17.

7.

The

st

udy

exam

ine

d po

tent

ial

conf

oun

ding

ef

fect

s of

at

ypic

al

cold

w

eat

her

on

air

pollu

tion/

mor

talit

y re

latio

nshi

ps.

Firs

t, ai

r po

llutio

n va

riabl

es

(SO

2,

CO

an

d B

S)

wer

e m

odel

ed

as

a fu

nctio

n of

la

gged

w

eath

er

varia

bles

. T

hese

var

iabl

es w

ere

dese

ason

aliz

ed

by r

egre

ssin

g o

n se

ine

and

cosi

ne v

aria

bles

. M

orta

lity

regr

essi

on

(OLS

) in

clud

ed

vario

us

lagg

ed

and

aver

aged

w

eat

her

and

pollu

tion

varia

bles

. A

naly

ses

wer

e co

nduc

ted

in th

e li

near

ra

nge

of m

orta

lity/

tem

pera

ture

rel

atio

nshi

p (1

5 to

0 d

egre

es C

).

Pol

lute

d da

ys w

ere

foun

d to

be

cold

er a

nd

less

w

indy

a

nd

rain

y th

an

usua

l. In

th

e re

gres

sion

of

m

orta

lity

on

the

mul

tiple

-la

gged

te

mpe

ratu

re,

win

d,

rain

, hu

mid

ity,

suns

hine

, S

O2,

C

O,

and

B

S,

cold

te

mpe

ratu

re w

as

asso

ciat

ed w

ith m

orta

lity

incr

ease

, bu

t no

t S

O2

or C

O.

BS

sho

we

d su

gges

tive

evid

ence

, th

ough

not

sta

tistic

ally

si

gnifi

cant

, of

asso

ciat

ion

at la

g 0

and

lag

1.

Per

cent

exc

ess

mor

talit

y 3%

(N

S)

incr

ease

in

da

ily

mor

talit

y pe

r 17

.7 µ

g/m

3 of

BS

(la

g 0

and

1).

report no. 4/11

102

And

erso

n et

al

. (1

996)

(A

nder

son

et a

l, 19

96)

Lond

on, U

K, 1

987-

1992

. B

S m

ean

15.

Tot

al,

card

iova

scul

ar,

and

resp

irato

ry m

orta

lity

serie

s w

ere

regr

esse

d on

B

S,

O3,

N

O2,

an

d S

O2,

ad

just

ing

for

sea

sona

l cyc

les,

da

y of

wee

k,

influ

enza

, ho

liday

s, t

empe

ratu

re,

hum

idity

, an

d au

toco

rrel

atio

n us

ing

Poi

sson

GLM

mod

el.

Bot

h O

3 (la

g 0)

an

d B

S

(lag

1)

we

re

sign

ifica

nt p

redi

ctor

s of

tot

al d

eath

s. O

3 w

as

also

pos

itive

ly s

igni

fican

tly a

ssoc

iate

d w

ith

resp

irato

ry a

nd c

ardi

ovas

cula

r de

aths

. T

he

effe

ct

size

es

timat

es

per

the

sam

e di

strib

utio

nal

incr

emen

t (1

0% t

o 90

%)

wer

e la

rger

fo

r O

3

than

fo

r B

S.

The

se

effe

cts

wer

e la

rger

in

war

m s

easo

n. S

O2

an

d N

O2

wer

e

not

cons

iste

ntly

a

ssoc

iate

d w

ith

mor

talit

y.

Per

cent

e

xce

ss

mor

talit

y 2.

8%

(1.4

, 4.

3) p

er 2

5 µ

g/m

3 BS

at

1-d

lag

for

tota

l dea

ths.

C

VD

(1

d): 1

.0%

(-1

.1, 3

.1).

R

espi

rato

ry

(1

d):

1.1%

(-

2.7,

5.

0).

And

erso

n et

al

. (2

001)

(A

nder

son

et a

l, 20

01)

The

W

est

Mid

land

s co

nurb

atio

n,

UK

. 19

94-

1996

. P

M m

eans

: P

M10

: 23

, P

M2.

5: 1

5, P

M10

-2.5:

9,

BS

: 13.

2.

Non

-acc

iden

tal

caus

e,

card

iova

scul

ar,

and

resp

irato

ry

mor

talit

y (a

s w

ell

as

hosp

ital

adm

issi

ons)

w

ere

ana

lyze

d fo

r th

eir

asso

ciat

ions

w

ith

PM

in

dic

es

and

gase

ous

pollu

tant

s us

ing

GA

M P

oiss

on m

odel

s ad

just

ing

for

seas

onal

cyc

les,

day

of

wee

k, a

nd w

eat

her.

Dai

ly

non-

acci

dent

al

mor

talit

y w

as

not

as

soci

ated

w

ith

PM

in

dice

s or

ga

seou

s po

lluta

nts

in t

he a

ll-ye

ar a

nal

ysis

. H

ow

ever

, al

l th

e P

M i

ndic

es (

exc

ept

coar

se p

artic

les)

w

ere

posi

tivel

y an

d si

gnifi

cant

ly a

ssoc

iate

d w

ith n

on-a

ccid

enta

l m

orta

lity

(age

ove

r 65

) in

the

war

m s

easo

n. O

f ga

seou

s po

lluta

nts,

N

O2

and

O3

wer

e po

sitiv

ely

and

sign

ifica

ntly

as

soci

ated

with

non

-acc

ide

ntal

mor

talit

y in

w

arm

sea

son

. T

wo

pollu

tant

mod

els

we

re

not

cons

ider

ed

beca

use

“so

few

as

soci

atio

ns w

ere

foun

d”.

Per

cent

exc

ess

mor

talit

y fo

r P

M10

, P

M2.

5, a

nd P

M10

-2.5 (

lag

0-1)

wer

e:

0.2%

(-1

.8,

2.2

) pe

r 24

.4

µg/

m3

PM

10,

0.6%

(-

1.5,

2.

7)

per

17.7

µ

g/m

3 PM

2.5,

and

-0.

6% (

-4.2

, 2.

3)

per

11.3

µg/

m3 P

M10

-2.5 i

n al

l-yea

r an

alys

is.

The

re

sults

fo

r se

ason

sp

ecifi

c an

alys

is

wer

e gi

ven

only

as

fig

ures

.

Kea

tinge

and

Don

alds

on

(200

1)

(Kea

tinge

an

dDon

alds

on, 2

001)

G

reat

er

Lond

on,

Eng

land

, 197

6-1

995.

B

S m

ean:

17.

7.

The

st

udy

exam

ine

d po

tent

ial

conf

oun

ding

ef

fect

s of

at

ypic

al

cold

w

eat

her

on

air

pollu

tion/

mor

talit

y re

latio

nshi

ps.

Firs

t, ai

r po

llutio

n va

riabl

es

(SO

2,

CO

an

d B

S)

wer

e m

odel

ed

as

a fu

nctio

n of

la

gged

w

eath

er

varia

bles

. T

hese

var

iabl

es w

ere

dese

ason

aliz

ed

by r

egre

ssin

g o

n se

ine

and

cosi

ne v

aria

bles

. M

orta

lity

regr

essi

on

(OLS

) in

clud

ed

vario

us

lagg

ed

and

aver

aged

w

eat

her

and

pollu

tion

varia

bles

. A

naly

ses

wer

e co

nduc

ted

in th

e li

near

ra

nge

of m

orta

lity/

tem

pera

ture

rel

atio

nshi

p (1

5 to

0 d

egre

es C

).

Pol

lute

d da

ys w

ere

foun

d to

be

cold

er a

nd

less

w

indy

a

nd

rain

y th

an

usua

l. In

th

e re

gres

sion

of

m

orta

lity

on

the

mul

tiple

-la

gged

te

mpe

ratu

re,

win

d,

rain

, hu

mid

ity,

suns

hine

, S

O2,

C

O,

and

B

S,

cold

te

mpe

ratu

re w

as

asso

ciat

ed w

ith m

orta

lity

incr

ease

, bu

t no

t S

O2

or C

O.

BS

sho

we

d su

gges

tive

evid

ence

, th

ough

not

sta

tistic

ally

si

gnifi

cant

, of

asso

ciat

ion

at la

g 0

and

lag

1.

Per

cent

exc

ess

mor

talit

y 3%

(N

S)

incr

ease

in

da

ily

mor

talit

y pe

r 17

.7 µ

g/m

3 of

BS

(la

g 0

and

1).

report no. 4/11

103

Goo

dman

et

al

., 20

04

(Goo

dman

et

al

, 20

04);

D

ublin

, Ir

elan

d,

1980

-19

96, B

S m

ean

40.

Thi

s st

udy

anal

ysed

the

acu

te a

nd m

ediu

m-t

erm

(w

eeks

to

mon

ths)

exp

osur

e ef

fect

s of

BS

and

te

mpe

ratu

re

on

tota

l an

d ca

use-

spec

ific

mor

talit

y. I

n th

e an

alys

is o

f th

e ac

ute

effe

cts

of

expo

sure

(3

-day

m

ean

BS

),

GA

M

Po

isso

n re

gres

sion

mod

els

for

the

log

coun

ts o

f da

ily

age-

stan

dard

ized

mor

talit

y ra

tes

wer

e ad

just

ed

for

met

eoro

logi

cal

mea

sure

s,

incl

udin

g te

mpe

ratu

re,

hum

idity

o

n th

e sa

me

and

prev

ious

day

, pl

us i

ndic

ato

rs f

or d

ay o

f w

eek

and

for

resp

irato

ry e

pide

mic

s.

The

cum

ulat

ive

effe

cts

of

tem

pera

ture

an

d pa

rtic

ulat

e ai

r po

llutio

n ov

er

40

days

w

ere

anal

yzed

si

mul

tane

ousl

y in

a

GA

M

mod

el

incl

udin

g di

strib

uted

la

g fu

nctio

ns

for

min

imum

te

mpe

ratu

re a

nd B

S.

D

aily

B

S

air

pollu

tion

conc

entr

atio

ns

wer

e m

easu

red

at 6

res

iden

tial m

onito

ring

stat

ions

.

The

ef

fect

s of

pa

rtic

ulat

e ai

r po

llutio

n on

m

orta

lity

wer

e s

tron

gest

on

the

day

of a

nd

the

few

day

s af

ter

expo

sure

but

ext

end

ed

out

thro

ugh

abou

t 40

day

s af

ter

expo

sure

. T

his

ext

ende

d a

ir po

llutio

n a

ssoc

iatio

n w

as

mos

t m

arke

d fo

r th

e el

derly

po

pula

tion

grou

ps a

nd f

or r

espi

rato

ry c

ause

s of

dea

th.

The

ext

ende

d f

ollo

w-u

p ef

fect

s w

ere

two

to

thre

e tim

es g

reat

er t

han

the

acut

e ef

fect

s re

port

ed i

n ot

her

stud

ies,

and

app

roac

hed

the

effe

cts

repo

rted

in

long

er-t

erm

sur

viva

l st

udie

s. T

he s

tudi

es o

n th

e ac

ute

effe

cts

of

air

pollu

tion

cou

ld h

ave

un

dere

stim

ated

the

to

tal

effe

ct o

f te

mpe

ratu

re a

nd p

artic

ulat

e ai

r po

llutio

n o

n m

orta

lity.

For

an

incr

emen

t of

10

µg/

m3 o

f B

S,

tota

l m

orta

lity

incr

ease

d by

0.

4% (

0.3,

0.6

) w

hen

only

acu

te

effe

cts

(3-d

ay

mea

n)

wer

e

cons

ider

ed a

nd

by 1

.1%

(0.

8, 1

.3)

whe

n co

nsid

eri

ng

deat

hs

in

the

40

days

af

ter

exp

osur

e.

Cor

resp

ondi

ng

estim

ates

w

ere

0.4%

(0

.2,

0.7)

an

d 1.

1%

(0

.7,

1.5)

for

CV

D m

orta

lity,

and

0.9

%

(0.5

to

1.2)

an

d 3.

6% (

3.0,

4.3

) fo

r re

spira

tory

mor

talit

y.

FIN

LAN

D

P

önkä

et

al

. (1

998)

(P

onka

et a

l, 1

998)

H

elsi

nki,

Fin

land

, 19

87-

1993

. T

SP

med

ian:

64

P

M10

med

ian:

28.

Tot

al a

nd c

ardi

ovas

cula

r d

eath

s, f

or a

ge g

roup

s <

65

and

65 +

, w

ere

rela

ted

to

PM

10,

TS

P,

SO

2,

NO

2,

and

O

3,

usin

g P

oiss

on

GLM

m

odel

ad

just

ing

for

tem

pera

ture

, re

lativ

e hu

mid

ity,

day-

of-w

eek,

te

mpo

ral

patte

rns,

ho

liday

an

d in

fluen

za e

pid

emic

s.

No

pollu

tant

si

gnifi

cant

ly

asso

ciat

ed

with

m

orta

lity

from

al

l ca

rdio

vasc

ular

or

C

VD

ca

uses

in

65+

yea

r ag

e gr

oup.

Onl

y in

age

<

65 y

ear

gro

up,

PM

10 a

ssoc

iate

d w

ith t

otal

an

d C

VD

de

aths

w

ith

4 an

d 5

d la

gs,

re

spec

tivel

y.

The

“s

igni

fican

t”

lags

w

ere

ra

ther

“sp

iky”

. O

3 w

as

also

ass

ocia

ted

with

C

VD

m

orta

lity

<65

ye

ars

grou

p w

ith

inco

nsis

tent

sig

ns a

nd l

ate

and

spik

y la

gs

(neg

ativ

e on

d 5

and

pos

itive

on

d 6)

.

18.8

%

(5.6

, 33

.2)

per

50

µg/

m3

PM

10

4 da

y la

g (o

ther

la

gs

nega

tive

or z

ero

).

report no. 4/11

104

Goo

dman

et

al

., 20

04

(Goo

dman

et

al

, 20

04);

D

ublin

, Ir

elan

d,

1980

-19

96, B

S m

ean

40.

Thi

s st

udy

anal

ysed

the

acu

te a

nd m

ediu

m-t

erm

(w

eeks

to

mon

ths)

exp

osur

e ef

fect

s of

BS

and

te

mpe

ratu

re

on

tota

l an

d ca

use-

spec

ific

mor

talit

y. I

n th

e an

alys

is o

f th

e ac

ute

effe

cts

of

expo

sure

(3

-day

m

ean

BS

),

GA

M

Po

isso

n re

gres

sion

mod

els

for

the

log

coun

ts o

f da

ily

age-

stan

dard

ized

mor

talit

y ra

tes

wer

e ad

just

ed

for

met

eoro

logi

cal

mea

sure

s,

incl

udin

g te

mpe

ratu

re,

hum

idity

o

n th

e sa

me

and

prev

ious

day

, pl

us i

ndic

ato

rs f

or d

ay o

f w

eek

and

for

resp

irato

ry e

pide

mic

s.

The

cum

ulat

ive

effe

cts

of

tem

pera

ture

an

d pa

rtic

ulat

e ai

r po

llutio

n ov

er

40

days

w

ere

anal

yzed

si

mul

tane

ousl

y in

a

GA

M

mod

el

incl

udin

g di

strib

uted

la

g fu

nctio

ns

for

min

imum

te

mpe

ratu

re a

nd B

S.

D

aily

B

S

air

pollu

tion

conc

entr

atio

ns

wer

e m

easu

red

at 6

res

iden

tial m

onito

ring

stat

ions

.

The

ef

fect

s of

pa

rtic

ulat

e ai

r po

llutio

n on

m

orta

lity

wer

e s

tron

gest

on

the

day

of a

nd

the

few

day

s af

ter

expo

sure

but

ext

end

ed

out

thro

ugh

abou

t 40

day

s af

ter

expo

sure

. T

his

ext

ende

d a

ir po

llutio

n a

ssoc

iatio

n w

as

mos

t m

arke

d fo

r th

e el

derly

po

pula

tion

grou

ps a

nd f

or r

espi

rato

ry c

ause

s of

dea

th.

The

ext

ende

d f

ollo

w-u

p ef

fect

s w

ere

two

to

thre

e tim

es g

reat

er t

han

the

acut

e ef

fect

s re

port

ed i

n ot

her

stud

ies,

and

app

roac

hed

the

effe

cts

repo

rted

in

long

er-t

erm

sur

viva

l st

udie

s. T

he s

tudi

es o

n th

e ac

ute

effe

cts

of

air

pollu

tion

cou

ld h

ave

un

dere

stim

ated

the

to

tal

effe

ct o

f te

mpe

ratu

re a

nd p

artic

ulat

e ai

r po

llutio

n o

n m

orta

lity.

For

an

incr

emen

t of

10

µg/

m3 o

f B

S,

tota

l m

orta

lity

incr

ease

d by

0.

4% (

0.3,

0.6

) w

hen

only

acu

te

effe

cts

(3-d

ay

mea

n)

wer

e

cons

ider

ed a

nd

by 1

.1%

(0.

8, 1

.3)

whe

n co

nsid

eri

ng

deat

hs

in

the

40

days

af

ter

exp

osur

e.

Cor

resp

ondi

ng

estim

ates

w

ere

0.4%

(0

.2,

0.7)

an

d 1.

1%

(0

.7,

1.5)

for

CV

D m

orta

lity,

and

0.9

%

(0.5

to

1.2)

an

d 3.

6% (

3.0,

4.3

) fo

r re

spira

tory

mor

talit

y.

FIN

LAN

D

P

önkä

et

al

. (1

998)

(P

onka

et a

l, 1

998)

H

elsi

nki,

Fin

land

, 19

87-

1993

. T

SP

med

ian:

64

P

M10

med

ian:

28.

Tot

al a

nd c

ardi

ovas

cula

r d

eath

s, f

or a

ge g

roup

s <

65

and

65 +

, w

ere

rela

ted

to

PM

10,

TS

P,

SO

2,

NO

2,

and

O

3,

usin

g P

oiss

on

GLM

m

odel

ad

just

ing

for

tem

pera

ture

, re

lativ

e hu

mid

ity,

day-

of-w

eek,

te

mpo

ral

patte

rns,

ho

liday

an

d in

fluen

za e

pid

emic

s.

No

pollu

tant

si

gnifi

cant

ly

asso

ciat

ed

with

m

orta

lity

from

al

l ca

rdio

vasc

ular

or

C

VD

ca

uses

in

65+

yea

r ag

e gr

oup.

Onl

y in

age

<

65 y

ear

gro

up,

PM

10 a

ssoc

iate

d w

ith t

otal

an

d C

VD

de

aths

w

ith

4 an

d 5

d la

gs,

re

spec

tivel

y.

The

“s

igni

fican

t”

lags

w

ere

ra

ther

“sp

iky”

. O

3 w

as

also

ass

ocia

ted

with

C

VD

m

orta

lity

<65

ye

ars

grou

p w

ith

inco

nsis

tent

sig

ns a

nd l

ate

and

spik

y la

gs

(neg

ativ

e on

d 5

and

pos

itive

on

d 6)

.

18.8

%

(5.6

, 33

.2)

per

50

µg/

m3

PM

10

4 da

y la

g (o

ther

la

gs

nega

tive

or z

ero

).

report no. 4/11

105

THE

NET

HER

LAN

DS

R

oem

er a

nd V

an W

ijnen

(2

001)

. (R

oem

er a

ndva

n W

ijnen

, 200

1)

Am

ster

dam

. 198

7-19

98.

BS

and

PM

10 m

eans

in

“b

ackg

roun

d”: 1

0 an

d 39

B

S m

ean

in “

traf

fic”

area

: 21

. (N

o P

M10

m

easu

rem

ents

av

aila

ble

at

traf

fic s

ites)

.

Dai

ly d

eath

s fo

r th

ose

wh

o liv

ed a

long

roa

ds

with

mor

e th

an 1

0,00

0 m

otor

veh

icle

, as

we

ll as

de

aths

for

tot

al p

opul

atio

n, w

ere

ana

lyze

d us

ing

data

fr

om

bac

kgro

und

and

tr

affic

m

onito

rs.

Poi

sson

G

AM

m

odel

w

as

used

ad

just

ing

for

seas

on,

day-

of-w

eek,

and

wea

ther

. B

S,

PM

10,

SO

2, N

O2,

CO

, and

O3

wer

e an

alyz

ed.

Cor

rela

tions

be

twee

n th

e ba

ckgr

oun

d m

onito

rs a

nd t

raffi

c m

onito

rs w

ere

mod

erat

e fo

r B

S (

r =

0.5

5) b

ut h

igh

er f

or N

O2 (

r =

0.

79)

and

O3

(r =

0.8

0).

BS

and

NO

2 w

ere

asso

ciat

ed w

ith m

orta

lity

in b

oth

tota

l an

d tr

affic

pop

ulat

ion.

Est

imat

ed

RR

for

tra

ffic

popu

latio

n u

sing

ba

ckgr

ound

si

tes

was

la

rger

tha

n th

e R

R f

or t

otal

pop

ulat

ion

usin

g ba

ckgr

ound

si

tes.

T

he

RR

fo

r to

tal

popu

latio

n us

ing

traf

fic

site

s w

as

smal

ler

that

R

Rs

for

tota

l po

pula

tion

usin

g ba

ckgr

ound

si

tes.

T

his

is

not

surp

risin

g si

nce

the

mea

n B

S

for

traf

fic

site

s w

ere

la

rger

than

for

back

grou

nd s

ites.

The

exc

ess

risk

per

100

µg

/m3 o

f B

S (

lag

1):

Tot

al

popu

latio

n us

ing

back

grou

nd

site

s:

38.3

%

(15.

3,

65.9

) T

raffi

c po

pula

tion

us

ing

ba

ckgr

ound

si

tes:

88

.7%

(2

0.7,

19

4.9)

T

otal

pop

ulat

ion

usin

g tr

affic

site

s:

12.2

% (

2.3,

23.

1).

Res

ults

for

tra

ffic

popu

latio

n u

sing

tr

affic

site

s no

t re

port

ed.

Hoe

k et

al.

(199

7) (

Hoe

k et

al,

1997

) R

otte

rdam

, th

e N

ethe

rland

s, 1

983-

1991

. T

SP

med

ian:

42,

B

S m

edia

n: 1

3.

Tot

al

mor

talit

y (a

lso

by

age

grou

p)

was

re

gres

sed

on T

SP

, F

e (f

rom

TS

P f

ilter

), B

S,

O3,

S

O2,

CO

, ad

just

ing

for

sea

sona

l cy

cles

, da

y-of

-w

eek,

in

fluen

za,

tem

pera

ture

, an

d hu

mid

ity

usin

g P

oiss

on G

AM

mod

el.

Dai

ly

deat

hs

wer

e m

ost

co

nsis

ten

tly

asso

ciat

ed w

ith T

SP

. T

SP

and

O3

effe

cts

wer

e “

inde

pend

ent”

of

SO

2 an

d C

O.

To

tal

iron

(fro

m T

SP

filt

er)

was

ass

ocia

ted

“less

co

nsis

tent

ly”

with

mor

talit

y th

an T

SP

was

. T

he

estim

ated

R

Rs

for

PM

in

dice

s w

ere

hi

gher

in w

arm

sea

son

tha

n in

col

d se

ason

.

Per

cent

exc

ess

mor

talit

y:

5.5%

(1

.1,

9.9)

pe

r 10

0 µ

g/m

3 T

SP

at l

ag 1

.

report no. 4/11

106

GER

MA

NY

W

ichm

ann

et a

l., (

2000

) (W

ichm

ann

et a

l, 20

00)

Erf

urt,

Ger

man

y.

1995

-19

98.

Num

ber

coun

ts (

NC

) an

d

mas

s co

nce

ntra

tions

(M

C)

of

ultr

afin

e pa

rtic

les

usin

g S

pect

rom

etry

ll M

obile

A

eros

ol

Sp

ectr

omet

ry

(MA

S).

M

AS

M

C

PM

2.5-

0.01

(m

ean

25.8

, m

edia

n

18.8

, IQ

R

19.9

).

Filt

er

mea

sure

men

ts

of

PM

10

(mea

n 38

.2,

med

ian

31

.0,

IQR

27

.7)

and

PM

2.5

(mea

n 26

.3,

med

ian

20.2

, IQ

R 1

8.5)

. M

AS

N

C2.

5-0

.01

(mea

n

17,9

66 p

er c

m3 ,

med

ian

14,7

69, I

QR

13,

269)

.

Tot

al

non-

acci

dent

al,

card

iova

scul

ar,

and

resp

irato

ry d

eath

s (m

ean

4.88

, 2.

87,

1.08

per

da

y, r

espe

ctiv

ely)

wer

e re

late

d to

par

ticle

mas

s co

ncen

trat

ion

and

num

ber

coun

ts i

n ea

ch s

ize

clas

s, a

nd t

o m

ass

conc

ent

ratio

ns o

f g

aseo

us

co-p

ollu

tant

s N

O2,

C

O,

SO

2,

usin

g G

AM

re

gres

sion

mod

els

adju

sted

for

tem

pora

l tre

nds,

da

y of

wee

k, w

eek

ly n

atio

nal

influ

enza

rat

es,

tem

pera

ture

an

d re

lativ

e hu

mid

ity.

Dat

a an

alyz

ed b

y se

ason

, ag

e gr

oup,

and

cau

se o

f de

ath

sepa

rate

ly.

Sin

gle

- da

y la

gs

and

poly

nom

ial

dist

ribut

ed l

ag m

odel

s (P

DL)

use

d.

Par

ticle

indi

ces

and

pollu

tan

ts f

itted

usi

ng li

near

, lo

g- t

rans

form

ed,

and

LOE

SS

tra

nsfo

rmat

ions

. T

wo-

pollu

tant

mod

els

with

a p

artic

le in

dex

and

a ga

seou

s po

lluta

nt w

ere

fitte

d. T

he “

best

” m

odel

w

as

that

ha

ving

th

e hi

ghes

t t-

stat

istic

, si

nce

ot

her

crite

ria

(e.g

., lo

g-lik

elih

ood

for

nest

ed

mod

els)

and

AIC

for

non

-nes

ted

mod

els

coul

d

not

be

appl

ied

due

to

diffe

rent

nu

mbe

rs

of

obse

rvat

ions

in

each

mod

el.

The

re s

houl

d be

lit

tle d

iffer

ence

bet

wee

n t

hes

e ap

proa

ches

and

re

sulti

ng d

iffer

ence

s in

res

ults

sho

uld

be

smal

l in

pr

actic

e.

Sen

sitiv

ity

anal

yses

in

clud

ed

stra

tifyi

ng

data

by

se

ason

, w

inte

r ye

ar,

age,

ca

use

of

deat

h,

or

tran

sfor

mat

ion

of

the

pollu

tion

varia

ble

(non

e,

loga

rithm

ic,

non-

para

met

ric s

moo

th).

Loss

of

stat

istic

al p

ow

er b

y us

ing

a sm

all

city

w

ith

a sm

all

num

ber

of

deat

hs

wa

s of

fset

by

a

dvan

tage

of

ha

ving

go

od

expo

sure

re

pres

enta

tion

fr

om

sing

le

mon

itorin

g si

te.

Sin

ce u

ltraf

ine

part

icle

s ca

n co

agul

ate

into

lar

ger

aggr

egat

es i

n a

few

ho

urs,

ultr

afin

e pa

rtic

le s

ize

and

num

bers

ca

n in

crea

se i

nto

the

fine

par

ticle

cat

egor

y,

resu

lting

in

so

me

ambi

gui

ty.

Sig

nific

ant

asso

ciat

ions

wer

e fo

und

bet

we

en m

orta

lity

and

ultr

afin

e pa

rtic

le N

C,

ultr

afin

e pa

rtic

le

MC

, fin

e pa

rtic

le

mas

s co

ncen

trat

ion,

or

S

O2

conc

entr

atio

n. T

he c

orre

latio

n be

twe

en

MC

0.01

-2.5 a

nd

NC

0.01

-0.1 w

as o

nly

mod

erat

e,

sugg

estin

g it

may

be

poss

ible

to

part

ially

se

para

te

effe

cts

of

ultr

afin

e an

d fin

e pa

rtic

les.

T

he

mos

t pr

edic

tive

sing

le-d

ay

effe

cts

are

eith

er i

mm

edia

te (

lag

0 or

1)

or

dela

yed

(lag

4 or

5),

but

cum

ulat

ive

effe

cts

char

acte

rized

by

PD

L ar

e la

rger

tha

n si

ngle

-da

y ef

fect

s.

The

si

gnifi

can

ce

of

SO

2 w

as

robu

st,

but

hard

to

exp

lain

as

a tr

ue c

ausa

l fa

ctor

si

nce

its

conc

entr

atio

ns

wer

e ve

ry

low

. A

ge w

as

an im

port

ant

mod

ifyin

g fa

ctor

, w

ith l

arge

r ef

fect

s at

age

s <

70

than

> 7

0 ye

ars.

R

espi

rato

ry

mor

talit

y ha

d a

high

er

RR

tha

n C

VD

mor

talit

y. A

lar

ge n

umbe

r of

m

odel

s w

ere

fit

ted,

w

ith

som

e si

gnifi

cant

fin

ding

s of

a

ssoc

iatio

n be

twee

n m

orta

lity

and

part

icle

mas

s or

num

ber

indi

ces.

Tot

al m

orta

lity

exce

ss d

eath

s:

Filt

er

PM

10

(lag

0-4)

: 6.

6 (0

.7,

12.8

) pe

r 50

µg/

m3 .

Filt

er

PM

2.5

(lag

0-1)

: 3.

0 (-

1.7,

7.

9).

MC

for

PM

0.01

-2.5 6

.2%

(1.

4, 1

1.2)

fo

r al

l yea

r W

inte

r: 9

.2%

(3.

0, 1

5.7)

S

prin

g: 5

.2%

(-2

.0, 1

2.8)

S

umm

er: -

4.7%

(-1

8.7,

11.

7)

Fal

l: 9.

7% (

1.9

, 18.

1)

For

ultr

afin

e P

M,

NC

0.01

-0.1 (

lag

0-4)

: A

ll Y

ear:

8.2

% (

0.3,

16.

9)

Win

ter:

9.7

% (

0.3,

19.

9)

Spr

ing:

10.

5%

(-1

.4, 2

3.9)

S

umm

er: -

13.9

% (

-29.

8, 5

.7)

F

all:

12.0

% (

2.1,

22.

7)

Bes

t sin

gle-

day

lag

per

25 µ

g/m

3 : P

M0.

01-0

.1: 3

.6%

(-0

.4, 7

.7)

P

M0.

01-2

.5: 3

.9%

(0.

0, 8

.0)

P

M2.

5: -

4.0%

(-7

.9, 0

)

PM

10: 6

.4%

(0

.3, 1

2.9)

.

report no. 4/11

107

Sto

lzel

et

al

. (2

003)

(S

tölz

el e

t al,

2003

) R

e-an

alys

is o

f th

e ab

ove

st

udy.

Re-

anal

ysis

o

f ab

ove

stud

y us

ing

GA

M

with

st

ringe

nt

con

verg

ence

cr

iteria

as

w

ell

as

GLM

/nat

ural

spl

ines

. T

he p

olyn

omia

l di

strib

uted

la

g m

odel

was

not

re-

anal

yzed

.

Ver

y lit

tle

chan

ge

in

PM

ris

k co

effic

ien

ts

whe

n G

AM

m

odel

s w

ith

strin

gent

co

nver

genc

e

crite

ria

wer

e us

ed.

Wh

en

GLM

/nat

ural

spl

ines

wer

e us

ed,

man

y of

th

e co

effic

ient

s fo

r nu

mbe

r co

ncen

trat

ions

sl

ight

ly

incr

ease

d,

but

the

co

effic

ient

s fo

r m

ass

conc

entr

atio

ns d

ecre

ased

slig

htly

.

Bes

t si

ngle

-day

la

g us

ing

G

AM

(s

trin

gent

) pe

r 25

µg/

m3 :

P

M0.

01-0

.1: 3

.6%

(-0

.4, 7

.7)

P

M0.

01-2

.5: 3

.8%

(-0

.1, 7

.8)

P

M2.

5: -

4.0%

(-7

.8, -

0.1)

P

M10

: 6.2

% (

0.1

, 12.

7)

Bes

t si

ngl

e-d

ay

lag

us

ing

GLM

/nat

ural

spl

ines

:

PM

0.01

-0.1: 3

.1%

(-1

.6, 7

.9)

P

M0.

01-2

.5: 3

.7%

(-0

.9, 8

.4)

P

M2.

5: -

3.4%

(-7

.9, 1

.4)

P

M10

: 5.3

% (

-1.8

, 12.

9).

Sto

lzel

et

al

., 20

06

(Sto

lzel

et a

l, 20

06)

Erf

urt,

Ger

man

y,

1995

-20

01.

To

stud

y th

e as

soci

atio

n b

etw

een

PM

0.01

-0.1 a

nd

PM

0.1-

2.5

and

to

tal

and

card

io-r

espi

rato

ry

mor

talit

y P

oiss

on

GA

M

mod

els

adju

ste

d fo

r tr

end,

sea

sona

lity,

inf

luen

za e

pide

mic

s, d

ay o

f th

e w

eek

, a

nd

met

eoro

logy

us

ing

smoo

th

func

tions

or

indi

cato

r va

riabl

es w

ere

used

.

Thi

s st

udy

show

s th

at

ultr

afin

e pa

rtic

les,

re

pres

entin

g fr

esh

com

bust

ion

part

icle

s,

coul

d be

an

impo

rtan

t co

mpo

nent

of

urba

n ai

r po

llutio

n a

ssoc

iate

d w

ith h

ealth

effe

cts.

In

fac

t, st

atis

tical

ly s

igni

fica

nt a

ssoc

iatio

ns

wer

e fo

und

be

twee

n e

leva

ted

ultr

afin

e pa

rtic

le n

umbe

r co

ncen

trat

ions

and

tot

al a

s w

ell

as c

ardi

o-re

spira

tory

mor

talit

y (la

g 4)

. N

o as

soci

atio

n be

twee

n fin

e pa

rtic

le

MC

an

d m

orta

lity

wa

s fo

und.

The

per

cent

mor

talit

y ex

cess

ris

k (la

g 4)

for

an

inc

rem

ent

of 9

,748

no

/cm

3 in P

M0.

1-2.

5, w

as 2

.9%

(0.

3,

5.5)

for

tot

al m

orta

lity,

and

3.1

%

(0.3

, 6.

0)

for

card

io-r

espi

rato

ry

mor

talit

y.

Rah

lenb

eck

and

Kah

l (1

996)

(R

ahle

nbec

k an

dKah

l, 19

96)

Eas

t B

erlin

, 19

81-1

989.

T

SP

(b

eta

atte

nuat

ion)

: 97

.

Tot

al m

orta

lity

(as

wel

l as

dev

iatio

ns f

rom

lon

g-w

ave

cyc

les)

wa

s re

gres

sed

(OLS

) on

TS

P a

nd

SO

2, a

djus

ting

for

day

of w

eek,

mon

th,

year

, te

mpe

ratu

re,

and

rela

tive

hum

idity

, us

ing

OLS

, w

ith o

ptio

ns t

o lo

g-tr

ansf

orm

pol

lutio

n, a

nd w

/ an

d w

/o d

ays

with

pol

lutio

n ab

ove

150

µg/

m3 .

Bot

h S

P

and

SO

2 w

ere

si

gnifi

cant

ly

asso

ciat

ed w

ith t

otal

mor

talit

y w

ith 2

day

lag

in

sing

le

pollu

tant

m

odel

. W

hen

both

po

lluta

nts

wer

e in

clud

ed,

thei

r co

effic

ien

ts

wer

e re

duce

d by

33%

and

46%

for

TS

P a

nd

SO

2, r

espe

ctiv

ely.

6.1%

per

100

µg/

m3 T

SP

at

lag

2.

report no. 4/11

108

BA

VAR

IA A

ND

CZE

CH

Pet

ers

et

al.

(200

0)

(Pet

ers

et a

l, 20

00)

A

high

ly

pollu

ted

coal

ba

sin

area

in

the

Cze

ch

Rep

ublic

an

d a

rura

l ar

ea

in

Ger

man

y,

nort

heas

t B

avar

ia

dist

ricts

. 198

2-1

994.

T

SP

m

ean:

12

1.1

and

51.6

, re

spec

tivel

y,

for

thes

e tw

o re

gio

ns.

PM

10

and

PM

2.5

wer

e al

so

mea

sure

d in

th

e co

al

basi

n du

ring

1993

-199

4 (m

ean:

65

.9

and

51.0

, re

spec

tivel

y).

Non

-acc

iden

tal

tota

l an

d ca

rdio

vasc

ular

dea

ths

(mea

n: 1

8.2

and

12.0

per

day

, fo

r th

e C

zech

an

d B

avar

ia a

reas

, re

spec

tivel

y).

The

AP

HE

A

appr

oach

(P

oiss

on G

LM m

odel

with

sin

e/co

sine

, te

mpe

ratu

re

as

a qu

adra

tic

func

tion,

re

lativ

e hu

mid

ity,

influ

enza

, da

y-of

-wee

k as

cov

aria

tes)

, as

we

ll as

GL

M w

ith n

atur

al s

plin

es f

or t

empo

ral

tren

ds

and

wea

ther

te

rms

wer

e co

nsid

ered

. Lo

garit

hm o

f T

SP

, S

O2,

NO

2, O

3, a

nd C

O (

and

PM

10 a

nd P

M2.

5 fo

r 19

93-1

994)

wer

e e

xam

ined

at

lags

0 th

roug

h 3

days

.

In t

he c

oal

bas

in (

i.e.,

the

Cze

ch R

epu

blic

po

llute

d ar

ea),

on

the

aver

age,

68%

of

the

TS

P w

as P

M1

0, a

nd m

ost

of P

M10

was

PM

2.5

(75%

).

For

th

e co

al

basi

n,

asso

ciat

ions

w

ere

foun

d b

etw

een

the

lo

garit

hm o

f T

SP

an

d al

l-cau

se m

orta

lity

at l

ag 1

or

2 d

ays

. S

O2

was

al

so

asso

ciat

ed

with

al

l-cau

se

mor

talit

y w

ith

slig

htly

lo

wer

si

gnifi

canc

e.

PM

10 a

nd P

M2.

5 w

ere

both

ass

ocia

ted

with

al

l-cau

se m

orta

lity

in 1

993-

1994

with

a l

ag

of 1

-day

. N

O2,

O3

and

CO

wer

e po

sitiv

ely

but

mor

e w

eak

ly a

ssoc

iate

d w

ith m

orta

lity

than

P

M

indi

ces

or

SO

2.

In

the

Bav

aria

n re

gion

, ne

ither

TS

P n

or S

O2

wa

s as

soci

ate

d w

ith m

orta

lity,

but

CO

(at

la

g 1-

day)

and

O3

(at

lag

0-da

y)

wer

e as

soci

ated

w

ith

all-

caus

e m

orta

lity.

Tot

al m

orta

lity

exce

ss d

eath

s pe

r 10

0 µ

g/m

3 incr

ease

in T

SP

for

the

C

zech

reg

ion:

3.

8% (

0.8,

6.9

) at

lag

2 f

or 1

982-

1994

pe

riod.

F

or

perio

d 19

93-

1994

, 9.

5 %

(1.

2, 1

8.5)

per

100

µ

g/m

3 inc

reas

e in

TS

P a

t la

g 1,

an

d 4.

8% (

0.7

, 9.

0) p

er 5

0 µ

g/m

3 in

crea

se i

n P

M10

; an

d 1.

4 (-

0.5,

3.

4) p

er 2

5 µ

g/m

3 PM

2.5.

Kot

šove

c et

al

. (2

000)

(K

otes

ovec

et

al, 2

000)

N

orth

ern

Boh

emia

, C

zech

R

epu

blic

, 19

82-

1994

. T

SP

mea

n: 1

21.

3.

Tot

al (

excl

udin

g ac

cide

nts

and

child

ren

youn

ger

than

1 y

ear)

, ca

use

spec

ific

(car

diov

ascu

lar

and

canc

er),

age

(65

and

les

s vs

. ot

herw

ise)

, an

d ge

nder

spe

cific

mor

talit

y se

ries

wer

e e

xam

ined

fo

r th

eir

asso

ciat

ions

with

TS

P a

nd S

O2 u

sing

lo

gist

ic

mod

el,

adju

stin

g fo

r se

ason

al

cycl

es,

influ

enza

ep

idem

ics,

lin

ear

an

d qu

adra

tic

tem

pera

ture

ter

ms.

Lag

s 0

thro

ugh

6 da

ys,

as

we

ll as

a 7

da

y m

ean

valu

es w

ere

exa

min

ed.

For

the

tot

al m

orta

lity,

TS

P,

but

not

SO

2,

wa

s as

soci

ated

. A

ppar

ent

diffe

renc

es

in

asso

ciat

ions

wer

e fo

und

bet

we

en m

en a

nd

wom

en.

For

ex

ampl

e,

for

age

belo

w

65

year

s,

card

iova

scul

ar

mor

talit

y w

as

asso

ciat

ed

with

T

SP

in

m

en

but

not

in

wom

en.

Tot

al

mor

talit

y pe

rcen

t ex

cess

de

aths

per

10

0 µ

g/m

3 inc

reas

e in

T

SP

at l

ag 2

wa

s 3.

4% (

0.5

, 6.4

).

FRA

NC

E

Zeg

hnou

n et

al

. (2

001)

(Z

eghn

oun

et a

l, 20

01)

Rou

en

and

Le

Hav

re,

Fra

nce.

199

0-19

95.

PM

13

mea

n:

32.9

fo

r R

ouen

, 36

.4

for

Le

Hav

re.

BS

m

ean:

18

.7

for

Rou

en,

16.3

fo

r Le

H

avre

.

Tot

al,

card

iova

scul

ar,

and

resp

irato

ry m

orta

lity

serie

s w

ere

regr

esse

d on

BS

, P

M13

, S

O2,

NO

2,

and

O3

in 1

- an

d 2-

pollu

tant

mod

els

usin

g G

AM

P

oiss

on m

odel

s ad

just

ing

for

seas

onal

tre

nds,

da

y of

wee

k, a

nd w

eath

er.

In

Rou

en,

O3,

SO

2,

and

NO

2 w

ere

each

si

gnifi

cant

ly

asso

ciat

ed

with

to

tal,

resp

irato

ry,

and

card

iova

scul

ar

mor

talit

y,

resp

ectiv

ely.

In

Le

H

avre

, S

O2

and

PM

13

wer

e as

soci

ated

w

ith

card

iova

scul

ar

mor

talit

y.

Ho

we

ver,

th

e la

ck

of

stat

istic

al

sign

ifica

nce

re

port

ed

for

mos

t of

th

ese

re

sults

may

be

in p

art

due

to t

he r

elat

ive

ly

smal

l po

pula

tion

size

of

th

ese

citie

s (4

30,0

00 a

nd 2

60,0

00, r

espe

ctiv

ely)

.

PM

13 t

otal

mor

talit

y R

Rs

per

IQR

w

ere

0.5

%

(-1.

1,

2.1)

in

R

ouen

(I

QR

=20

.6,

lag

1) a

nd 1

.9%

(-0

.8,

7.4)

in L

e H

avre

(IQ

R=

23.9

, 1-

day

lag

). B

S t

ota

l m

orta

lity

RR

s pe

r IQ

R

wer

e 0.

5%

(-1.

8,

2.9)

in

R

ouen

(IQ

R=

14.2

, 1-

day

lag)

and

0.

3%

(-1.

6,

2.2)

in

Le

H

avre

(I

QR

=11

.5, l

ag

0-1)

.

report no. 4/11

109

Le T

ertr

e et

al.,

200

2 (L

e T

ertr

e et

al,

2002

b)

Nin

e F

renc

h C

ities

, 19

90-1

995.

B

S

med

ian

ra

ngin

g be

twee

n

12.7

-16.

0 μg

/m3 (

base

d on

5 c

ities

, on

ly).

Thi

s st

udy

exa

min

ed t

he s

hort

-ter

m e

ffect

s of

air

pollu

tion

(BS

, S

O2,

NO

2, O

3) o

n m

orta

lity,

usi

ng

Poi

sson

tim

e-se

ries

regr

essi

ons,

con

trol

ling

for

tren

ds

in

seas

ons,

ca

lend

ar

effe

cts,

in

fluen

za

epid

emic

s, t

em

pera

ture

, an

d hu

mid

ity.

Lag

0-1

w

as

used

for

all t

he c

ities

.

Sig

nific

ant

an

d po

sitiv

e as

soci

atio

ns

we

re

foun

d be

twee

n to

tal

daily

de

aths

and

the

fo

ur

air

pollu

tion

indi

cato

rs

cons

ider

ed.

Sim

ilar

resu

lts

wer

e

obta

ined

fo

r ca

rdio

vasc

ular

m

orta

lity.

E

xcep

t fo

r S

O2,

po

sitiv

e bu

t no

n si

gnifi

cant

as

soci

atio

ns

wer

e fo

und

with

res

pira

tory

mor

talit

y.

The

res

ults

wer

e co

nsis

tent

am

ong

all

the

citie

s co

nsid

ered

.

A 5

0 μg

/m3 in

crea

se in

BS

(la

g 0-

1) w

as a

ssoc

iate

d w

ith 2

.9%

(1.

3,

4.4)

in

crea

se

in

tota

l m

ort

ality

, 3.

1% (

0.5,

5.5

) in

car

diov

ascu

lar

mor

talit

y, a

nd 2

.7%

(-2

.6,

8.3)

in

resp

irato

ry

mor

talit

y.

Cor

resp

ondi

ng

estim

ates

af

ter

excl

usio

n of

Par

is w

ere

4.6

% (

1.9,

7.

4),

5.5%

(0.

9, 1

0.4)

and

11.

1%

(1.3

, 21.

9), r

espe

ctiv

ely.

E

ilste

in

et

al.,

2004

(E

ilste

in e

t al,

2004

) N

ine

Fre

nch

Citi

es,

1990

-199

7.

Upd

ate

of

the

abov

e st

udy.

B

S

and

PM

10

leve

l in

dica

tors

not

giv

en.

BS

da

ta w

ere

ava

ilabl

e fo

r 6

ci

ties

and

P

M10

fo

r 3

ci

ties.

Thi

s st

udy

exa

min

ed t

he s

hort

-ter

m e

ffect

s of

air

pollu

tion

(PM

10,

BS

, S

O2,

NO

2, C

O,

O3)

on

tota

l, ca

rdio

vasc

ular

and

res

pira

tory

mor

talit

y, u

sing

P

oiss

on G

AM

, ad

just

ing

for

tren

ds i

n se

aso

ns,

day

of

wee

k,

holid

ays,

in

fluen

za

epid

em

ics,

te

mpe

ratu

re,

and

hum

idity

. E

xces

s ris

ks a

t la

g 0-

1 an

d la

g 0-

5 w

ere

sho

wn.

Sig

nific

ant

di

rect

as

soci

atio

ns

wer

e fo

und

for

all

the

air

pollu

tion

ind

exes

oth

er t

han

C

O.

The

per

cent

exc

ess

ris

ks f

or

a 10

μg

/m3 in

crea

se in

BS

wer

e 0.

8 fo

r to

tal

mor

talit

y,

0.5

fo

r ca

rdio

vasc

ular

an

d 0.

7 (n

on-

sign

ifica

nt,

NS

) fo

r re

spira

tory

m

orta

lity

at

lag

0-

1.

Cor

resp

ondi

ng

estim

ates

at

lag

0-5

wer

e 1.

2,

1.2

and

2.1,

re

spec

tivel

y. T

he p

erce

nt e

xce

ss

risks

for

a 1

0 μg

/m3 i

ncre

ase

in

PM

10 w

ere

0.8

for

tota

l, 0.

3 (N

S)

for

card

iova

scul

ar

and

0.6

(NS

) fo

r re

spira

tory

mor

talit

y at

lag

0-1.

C

orre

spon

din

g es

timat

es a

t la

g 0-

5 w

ere

1.0,

0.

3 (N

S)

and

1.

9,

resp

ectiv

ely.

report no. 4/11

110

ITA

LY

Z

anob

etti

et

al.

(200

0)

(Zan

obet

ti et

al,

2000

) M

ilan,

Ital

y. 1

980

-198

9.

TS

P m

ean:

14

2.

The

foc

us o

f th

is s

tudy

was

to

quan

tify

mo

rtal

ity

disp

lace

men

t us

ing

wha

t th

ey

term

ed

“GA

M

dist

ribut

ed

lag

mod

els”

(s

moo

thin

g te

rm

was

fit

ted

with

pe

naliz

ed

splin

es).

N

on-a

ccid

enta

l to

tal

deat

hs w

ere

regr

esse

d on

sm

ooth

fu

nctio

n of

TS

P d

istr

ibut

ed o

ver

the

sam

e da

y an

d th

e pr

evio

us 4

5 da

ys u

sing

pen

aliz

ed s

plin

es f

or t

he

smoo

th

term

s an

d se

ason

al

cycl

es,

tem

pera

ture

, hu

mid

ity,

day-

of-

wee

k, h

olid

ays,

an

d in

fluen

za

epid

emic

s.

The

m

orta

lity

disp

lace

men

t w

as

mod

elle

d as

th

e

initi

al

posi

tive

incr

eas

e,

nega

tive

re

boun

d (d

ue

to

depl

etio

n),

follo

wed

by

an

othe

r po

sitiv

e co

effic

ient

pe

riod,

an

d th

e su

m

of

the

thre

e ph

ases

wer

e co

nsid

ered

as

the

tota

l cu

mul

ativ

e

effe

ct.

TS

P w

as p

ositi

vely

ass

ocia

ted

with

mor

talit

y up

to

13

da

ys,

follo

wed

by

ne

arly

ze

ro

coef

ficie

nts

bet

we

en 1

4 an

d 20

day

s, a

nd

then

fo

llow

ed

by

smal

ler

but

posi

tive

coef

ficie

nts

up

to t

he 4

5th

day

(max

imum

ex

amin

ed)

. T

he s

um o

f th

ese

coef

ficie

nts

w

as

over

thr

ee t

imes

larg

er t

han

that

for

the

si

ngle

-day

est

imat

e.

Tot

al

mor

talit

y pe

rcen

t in

crea

se

estim

ates

pe

r IQ

R

incr

ease

in

T

SP

: 2.

2%

(1.

4, 3

.1)

for

sing

le-

day

mod

el;

6.7%

(3

.8,

9.6)

fo

r di

strib

uted

lag

mod

el.

Ros

si

et

al.

(199

9)

(Ros

si e

t al,

199

9)

Mila

n, It

aly,

19

80-1

989

T

SP

(P

M13

be

ta

atte

nuat

ion)

: 142

.

Spe

cific

ca

uses

of

de

ath

(res

pira

tory

, re

spira

tory

in

fect

ions

, C

OP

D,

circ

ulat

ory,

ca

rdia

c, h

eart

fai

lure

, an

d A

MI)

wer

e re

late

d to

T

SP

, S

O2,

a

nd

NO

2,

adju

stin

g fo

r se

ason

al

cycl

es,

tem

per

atur

e,

and

hum

idity

, us

ing

P

oiss

on G

AM

mod

el.

All

thre

e po

lluta

nts

wer

e as

soci

ated

with

all

caus

e m

orta

lity.

C

ause

-spe

cific

an

alys

is

wa

s co

nduc

ted

for

TS

P

only

. R

espi

rato

ry

infe

ctio

n an

d he

art

failu

re d

eath

s w

ere

both

as

soci

ated

with

TS

P o

n th

e co

ncur

rent

day

, w

here

as

the

as

soci

atio

ns

for

myo

card

ial

infa

rctio

n an

d C

OP

D d

eath

s w

ere

foun

d fo

r th

e av

erag

e of

3 to

4 d

ay p

rior

TS

P.

3.3%

(2

.4,

4.3)

pe

r 10

0 µ

g/m

3 T

SP

at l

ag 0

.

Mic

helo

zzi

et

al.

(199

8)

(Mic

helo

zzi e

t al

, 199

8)

Rom

e, I

taly

, 19

92-1

995.

T

SP

(P

M13

be

ta

atte

nuat

ion)

: 84.

Tot

al m

orta

lity

was

rel

ated

to

PM

13,

SO

2, N

O2,

C

O,

and

O3,

us

ing

Poi

sson

G

AM

m

odel

, ad

just

ing

for

seas

onal

cy

cles

, te

mpe

ratu

re,

hum

idity

, da

y-of

-wee

k, a

nd h

olid

ay.

Ana

lysi

s of

m

orta

lity

by p

lace

of

resi

denc

e, s

easo

n, a

ge,

plac

e of

dea

th (

in o

r ou

t of

hos

pita

l), a

nd c

ause

w

as

also

con

duc

ted.

PM

13

an

d

NO

2 w

ere

mo

st

cons

iste

ntly

as

soci

ated

w

ith

mor

talit

y.

CO

an

d O

3 co

effic

ient

s w

ere

posi

tive,

SO

2 co

effic

ient

s ne

gativ

e.

RR

es

timat

es

high

er

in

the

war

mer

sea

son.

RR

s si

mila

r fo

r in

- an

d ou

t-of

hos

pita

l de

aths

.

1.9%

(0.

5, 3

.4)

per

50 µ

g/m

3 PM

13

at la

g 0.

report no. 4/11

111

Big

geri

et

al.

(200

5)

(Big

geri

et a

l, 20

05)

Eig

ht

citie

s of

N

orth

, C

entr

e an

d S

out

h of

Ital

y 19

90-1

999.

P

M10

m

ean

daily

co

ncen

trat

ion:

T

urin

, 91-

94: 7

7.6

Tur

in, 9

5-98

: 63.

8 M

ilan,

90-

94: 6

1.8

Mila

n, 9

5-97

: 45.

2 V

eron

a, 9

5-99

: 36.

5 R

aven

na, 9

1-95

: 59.

1 B

olog

na, 9

6-9

8: 4

1.2

Flo

renc

e, 9

6-98

: 40.

3 R

ome,

92-

94: 6

9.7

Pal

erm

o, 9

7-99

: 42.

9.

Met

a-an

alys

is

of

shor

t-te

rm

effe

cts

of

air

pollu

tion

on m

orta

lity

(all

caus

es,

card

iova

scul

ar

caus

es a

nd r

espi

rato

ry c

ause

s) i

n ei

ght

Italia

n ci

ties

from

199

0 to

199

9. D

aily

con

cent

ratio

ns o

f po

lluta

nts

wer

e co

llect

ed.

A g

ener

aliz

ed l

inea

r m

odel

ad

just

ed

for

age,

da

y of

th

e

wee

k,

holid

ays,

in

fluen

za

epid

em

ics,

m

eteo

rolo

gica

l va

riabl

es,

and

sea

sona

lity

pat

tern

wa

s fit

ted

for

PM

10 a

nd o

the

r co

-pol

luta

nt (

SO

2, N

O2,

CO

, an

d O

3).

City

-spe

cific

and

fix

ed-

and

rand

om-e

ffect

s po

oled

es

timat

es

wer

e sh

own.

La

g 0-

1 w

as

used

fo

r m

orta

lity.

F

ixed

- an

d ra

ndom

-eff

ects

m

odel

s w

ere

show

n.

A s

igni

fican

t di

rect

ass

ocia

tion

was

fou

nd

betw

een

PM

10

and

tota

l n

atur

al

mor

talit

y.

The

effe

ct o

f P

M10

was

gre

ater

dur

ing

the

war

m s

easo

n a

nd f

or t

he e

lder

ly.

A N

orth

-S

outh

gra

dien

t in

ris

k w

as o

bser

ved

for

tota

l na

tura

l m

orta

lity.

A

si

gnifi

cant

as

soci

atio

n w

as

also

sh

own

fo

r ca

rdio

vasc

ular

a

nd

resp

irato

ry m

orta

lity.

Sim

ilar

incr

ease

d ris

ks

wer

e fo

und

fo

r th

e ot

her

cons

ider

ed

co-

pollu

tant

s. T

he

effe

cts

of P

M10

sho

wed

the

hi

ghes

t int

er-c

ity v

aria

bilit

y.

Per

cent

ex

cess

m

orta

lity

for

10

µg/

m3 c

hang

e in

PM

10 (

lag

0-1)

: A

ll na

tura

l cau

ses

Fix

ed-e

ffect

s: 0

.85%

(0.

52,

1.18

) R

ando

m-e

ffect

s:

0.98

%

(0.3

5,

1.61

) C

VD

cau

ses

Fix

ed-e

ffect

s: 0

.97%

(0.

45,

1.50

) R

ando

m-e

ffect

s:

1.21

%

(0.3

2,

2.10

) R

espi

rato

ry c

aus

es

Fix

ed-e

ffect

s: 1

.74%

(0.

44,

3.05

) R

ando

m-e

ffect

s:

1.41

%

(-1.

41,

4.32

).

Sta

fogg

ia

et

al.,

2005

(S

tafo

ggia

et

al, 2

005)

R

ome,

Ita

ly,

1998

-200

0 P

M10

mea

n: 5

2.1;

P

NC

m

ean

51,6

69 n

o/cm

3 In

pa

rt,

rean

alys

is

of

abov

e st

udy

as

time

serie

s.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

daily

am

bien

t ai

r po

llutio

n

leve

ls

(PN

C,

as

a

prox

y of

ultr

afin

e pa

rtic

les,

PM

10,

CO

, N

O2

and

O3)

and

the

occ

urre

nce

of f

atal

, ou

t-of

-hos

pita

l co

rona

ry

even

ts

(5,1

44

subj

ects

) an

d fa

tal

hosp

italis

ed c

oron

ary

even

ts (

1,41

1 su

bjec

ts),

us

ing

a G

AM

P

oiss

on

mod

el

adju

stin

g fo

r te

mpo

ral

tren

d,

tem

pera

ture

, hu

mid

ity,

day

of

wee

k,

holid

ays

, an

d po

pula

tion

redu

ctio

n in

su

mm

er m

onth

s. L

ags

0, 1

, 0-

1 an

d 0-

4 w

ere

cons

ider

ed.

Sig

nific

ant

di

rect

as

soci

atio

ns

wer

e fo

und

for

PN

C,

PM

10 a

nd C

O,

and

bot

h ou

t-of

-ho

spita

l de

ath

s an

d fa

tal

coro

nary

eve

nts.

T

he a

ssoc

iatio

ns w

ere

stro

nger

in

subj

ects

ol

der

than

65

year

s.

Incr

ease

in

risk

of o

ut-o

f-h

ospi

tal

coro

nary

de

ath

as

soci

ated

w

ith

29.7

μg/

m3 (

IQR

) P

M10

: 7.

0% (

2.9,

11.

2) a

t lag

0

6.4%

(2.

4, 1

0.6)

at l

ag 1

8.

1% (

3.6,

12.

9) a

t lag

0-1

9.

6% (

4.4,

15.

2) a

t lag

0-4

In

crea

se i

n ris

k fo

r an

inc

rem

ent

in P

NC

of 2

8,00

1 no

/cm

3 (IQ

R):

8.

1% (

3.0,

13.

4) a

t lag

0

4.0%

(-1

.1, 9

.3)

at la

g 1

7.8%

(2.

0, 1

4.0)

at l

ag 0

-1

8.3%

(2.

1, 1

4.9)

at l

ag 0

-4

The

in

crea

ses

in

risk

of

fata

l co

rona

ry

eve

nts

at

lag

0

w

ere

5.0%

(1.

3, 8

.9)

for

PM

10 a

nd 8

.2%

(3

.6, 1

3.1)

for

PN

C.

report no. 4/11

112

For

astie

re

et

al.,

2005

(F

oras

tiere

et a

l, 20

05)

Rom

e, I

taly

, 19

98-2

001,

P

M10

mea

n 51

.0.

Thi

s st

udy

inve

stig

ated

whe

ther

soc

ial

cla

ss i

s an

effe

ct m

odifi

er o

f th

e as

soci

atio

n b

etw

een

P

M10

and

dai

ly m

orta

lity.

Sub

ject

s in

clud

ed

wer

e 83

,253

res

iden

ts o

f R

ome

aged

≥35

yea

rs w

ho

died

for

natu

ral c

ause

s be

twee

n 19

98 a

nd 2

001.

A

ca

se-c

ross

over

de

sign

w

as

used

. C

ontr

ol

days

w

ere

sele

cted

us

ing

th

e tim

e-st

ratif

ied

appr

oach

: al

l sa

me

days

of

the

wee

k w

ithin

tha

t m

onth

(of

the

sam

e ye

ar)

wer

e ch

osen

. La

g 0–

1 w

as

cons

ider

ed.

Con

ditio

nal

log

istic

reg

ress

ion

anal

ysis

was

use

d af

ter

allo

wa

nce

for

appa

rent

te

mpe

ratu

re o

n th

e in

dex

day,

and

its

diffe

renc

e fr

om t

he a

vera

ge o

f th

e pr

evio

us 3

day

s’ v

alue

s,

influ

enza

ep

idem

ics,

ho

liday

s,

and

pop

ulat

ion

re

duct

ion

in s

umm

er m

onth

s. A

s a

surr

ogat

e fo

r in

divi

dual

soc

ioec

onom

ic s

tatu

s (S

ES

) tw

o ar

ea-

base

d in

dica

tors

wer

e us

ed:

inco

me

and

SE

S o

f th

e po

pula

tion

liv

ing

in t

he s

ame

cens

us b

lock

, as

der

ived

from

the

2001

cen

sus.

A

sign

ifica

nt

exce

ss

risk

was

fo

und

fo

r P

M10

. S

ubje

cts

in t

he lo

w,

mid

-low

, m

id-h

igh

cate

gorie

s of

bo

th

inco

me

and

soci

o-ec

onom

ic s

tatu

s sh

ow

ed a

n ef

fect

of

PM

10

very

co

nsis

tent

w

ith

the

over

all

estim

ate

whe

reas

th

ose

in

the

hig

h ca

tego

ry

had

ef

fect

est

imat

es c

lose

to th

e n

ull.

The

in

crea

se

in

mor

talit

y as

soci

ated

w

ith a

n in

crem

ent

of

10 μ

g/m

3 of

PM

10 (

lag

0-1

) w

as

1.1%

(0.

7, 1

.6).

T

here

w

as

a st

atis

tical

ly

sign

ifica

nt

effe

ct

mod

ifica

tion

of

soci

al

clas

s on

a

mul

tiplic

ativ

e sc

ale.

For

the

low

est

and

high

est

quin

tile

of

SE

S

the

incr

ease

s w

ere

1.9

%

and

0.0%

fo

r th

e hi

ghes

t qu

intil

e.

Cor

resp

ondi

ng

valu

es f

or t

he l

owes

t an

d hi

ghes

t qu

intil

es

of

inco

me

wer

e

1.4%

an

d 0.

1%.

San

seba

stia

no

et

al.

(200

3)

(San

seba

stia

no

et

al,

2003

) P

arm

a, It

aly,

199

2-20

01.

mea

n da

ily

conc

entr

atio

n:

PM

10

(199

8-20

01:

from

39

,63

in 1

998

to 5

7.68

in 2

001;

T

SP

: fr

om 4

6.92

in

1996

to

62.

39 in

19

92.

Thi

s st

udy

exam

ined

the

rel

atio

nshi

p be

twee

n T

SP

an

d ot

her

co

-pol

luta

nts

(CO

, N

O2,

an

d S

O2)

, an

d ge

ner

al m

orta

lity

in t

he c

ity o

f P

arm

a (p

opul

atio

n 17

0,00

0).

The

ex

cess

ris

k of

ho

spita

l ad

mis

sion

was

no

t an

alys

ed f

or P

M10

si

nce

info

rmat

ion

for

PM

10 w

as

avai

labl

e fo

r th

e pe

riod

1998

-200

1, o

nly.

A

dire

ct

ass

ocia

tion

has

been

sh

ow

n

betw

een

TS

P,

SO

2 an

d ge

ner

al m

orta

lity.

P

erce

nt e

xce

ss r

isk

(95

% C

I) o

f to

tal

mor

talit

y fo

r 1

µg/

m3

incr

emen

t of

T

SP

: 0.

14%

(0

.08,

0.

23).

SPA

IN

T

obia

s an

d

Cam

pbel

l (1

999)

(T

obia

s an

dCam

pbel

l, 19

99)

Bar

celo

na,

Spa

in.

1991

-19

95.

BS

(no

dat

a di

strib

utio

n

wa

s re

port

ed).

Thi

s st

udy

exa

min

ed t

he s

ens

itivi

ty o

f es

timat

ed

tota

l m

orta

lity

effe

cts

of

BS

to

d

iffer

ent

appr

oach

es

to

mod

elin

g in

fluen

za

epid

emic

s:

(1)

with

a s

ingl

e du

mm

y va

riabl

e; (

2) w

ith t

hree

du

mm

y va

riabl

es;

(3)

usin

g da

ily

num

ber

of

case

s of

in

fluen

za.

Poi

sson

G

LM

regr

essi

on

used

to

mod

el t

otal

dai

ly m

ort

ality

, ad

just

ing

for

wea

ther

, lo

ng-t

erm

tr

end,

an

d se

ason

, ap

pare

ntly

follo

win

g A

PH

EA

pro

toco

l.

Usi

ng

the

re

port

ed

daily

nu

mbe

r of

in

fluen

za c

ase

s re

sulte

d in

a b

ette

r fit

(i.e

., a

low

er

AIC

) th

an

thos

e us

ing

dum

my

varia

bles

. In

th

e “b

ette

r”

mod

el,

the

BS

co

effic

ient

w

as

abou

t 10

%

smal

ler

than

th

ose

in t

he m

odel

s w

ith d

umm

y in

fluen

za

varia

bles

, bu

t re

mai

ned

sign

ifica

nt.

Lags

not

re

port

ed.

Tot

al m

orta

lity

exce

ss d

eath

s pe

r 25

µ

g/m

3 in

crea

se

in

BS

: 1.

37

(0.2

0, 2

.56)

for

mod

el u

sing

the

da

ily

case

of

in

fluen

za;

1.71

(0

.53,

2.9

1) f

or m

odel

with

thr

ee

influ

enza

dum

my

varia

bles

.

report no. 4/11

113

Alb

erdi

O

drio

zola

et

al

. (1

998)

(A

lber

di

Odr

iozo

la e

t al,

1998

) M

adrid

, S

pain

, 19

86-

1992

. T

SP

(b

eta

atte

nuat

ion)

: 47

fo

r av

erag

e of

2

st

atio

ns.

Tot

al,

resp

irato

ry,

and

card

iova

scul

ar

dea

ths

wer

e re

late

d

to

TS

P

and

SO

2.

Mul

tivar

iate

au

tore

gres

sive

in

tegr

ated

m

ovin

g av

erag

e m

odel

s us

ed t

o ad

just

for

sea

son,

tem

pera

ture

, re

lativ

e hu

mid

ity, a

nd in

fluen

za e

pide

mic

s.

TS

P

(lag

1)

and

SO

2 (la

g 3)

w

ere

inde

pend

ently

ass

ocia

ted

with

mor

talit

y.

4.8%

(1

.8,

7.7)

pe

r 10

0 µ

g/m

3 T

SP

at l

ag 1

.

Día

z et

al.

(199

9) (

Dia

z et

al,

1999

) M

adrid

, S

pain

, 19

90-

1992

. T

SP

(no

dat

a di

strib

utio

n

wa

s re

port

ed).

Non

-acc

iden

tal,

resp

irato

ry,

and

card

iova

scul

ar

deat

hs (

mea

n =

62.

4, 6

.3,

and

23.8

pe

r da

y,

resp

ectiv

ely)

. A

uto-

Reg

ress

ive

Inte

grat

ed

Mov

ing

Ave

rage

(A

RIM

A)

mod

els

fit

to

both

de

pend

ent

and

inde

pend

ent

varia

bles

fir

st

to

rem

ove

auto

-cor

rela

tion

and

seas

onal

ity

(i.e.

, pr

e-w

hite

ning

),

follo

wed

by

ex

amin

ing

cros

s-co

rrel

atio

n to

fin

d op

timal

lags

. M

ultiv

aria

te O

LS

mod

els

thus

in

clud

ed

AR

IMA

co

mpo

nent

s,

seas

onal

cy

cles

(s

ine/

cosi

ne),

V

-sha

ped

tem

pera

ture

, an

d op

timal

la

gs

foun

d fo

r po

llutio

n an

d w

eath

er v

aria

bles

. T

SP

, S

O2,

NO

2,

and

O3

wer

e ex

amin

ed.

S

easo

n-sp

ecifi

c an

alys

es w

ere

als

o co

nduc

ted.

TS

P w

as s

ign

ifica

ntly

ass

ocia

ted

with

non

-ac

cide

ntal

mo

rtal

ity a

t la

g 0

for

yea

r ar

ound

an

d w

inte

r, b

ut w

ith a

lag

1 i

n su

mm

er.

A

sim

ilar

patte

rn

wa

s se

en

for

circ

ulat

ory

deat

hs.

For

re

spira

tory

m

orta

lity,

a

sign

ifica

nt a

ssoc

iatio

n w

ith T

SP

was

fou

nd

only

in

sum

mer

(la

g 0)

. S

O2,

NO

x, a

nd

NO

2 sh

ow

ed

sim

ilar

asso

ciat

ions

w

ith

non-

acci

dent

al

dea

ths

at

lag

0 da

y.

O3

asso

ciat

ions

w

ith

non-

acci

dent

al

mor

talit

y w

as

U-s

hape

d, w

ith i

ncon

sist

ent

lags

(1,

4,

and

10).

For

no

n-ac

cide

ntal

m

ort

ality

, ex

cess

de

ath

s w

as

7.4%

(c

onfid

ence

ban

ds n

ot r

epor

ted;

p

< 0

.05)

per

100

µg/

m3 T

SP

at

lag

0.

Stud

ies

in s

ubje

cts

with

CO

PD/a

sthm

a

G

arci

a-A

ymer

ich

et

al.

(200

0) (

Gar

cia-

Aym

eric

h

et a

l, 20

00)

Bar

celo

na,

Spa

in.

1985

-19

89.

BS

(no

dat

a di

strib

utio

n

wa

s re

port

ed).

Dai

ly t

otal

(m

ean

= 1

.8/d

ay)

, re

spira

tory

, an

d ca

rdio

vasc

ular

m

orta

lity

coun

ts

of

a co

hort

(9

,987

su

bjec

ts)

with

C

OP

D

or

asth

ma

w

ere

asso

ciat

ed w

ith B

S (

24-h

r),

SO

2 (2

4- h

r an

d 1-

hr

max

), N

O2

(24-

hr a

nd 1

-hr

max

), O

3 (1

-hr

ma

x),

tem

pera

ture

, an

d re

lativ

e hu

mid

ity.

Poi

sson

G

LM r

egre

ssio

n m

odel

s us

ing

AP

HE

A p

roto

col

wer

e u

sed.

The

res

ultin

g R

Rs

wer

e co

mpa

red

with

thos

e of

the

gen

eral

pop

ulat

ion.

Dai

ly

mor

talit

y in

C

OP

D

patie

nts

was

as

soci

ated

with

all

six

pollu

tion

indi

ces.

Th

is

asso

ciat

ion

was

str

onge

r th

an in

the

gen

era

l po

pula

tion

only

for

dai

ly 1

-hr

max

of

SO

2,

daily

1-h

r m

ax a

nd d

aily

mea

ns o

f N

O2.

BS

an

d da

ily m

eans

of

SO

2 sh

owed

sim

ilar

or

wea

ker

asso

ciat

ions

fo

r C

OP

D

patie

nts

th

an fo

r th

e ge

nera

l pop

ulat

ion.

Tot

al

mor

talit

y pe

rcen

t in

crea

se

per

25 µ

g/m

3 inc

reas

e of

BS

at

lag

0-3:

2.

76%

(1

.31,

4.

23)

in

ge

nera

l po

pula

tion,

and

1.1

4% (

-4.

4, 6

.98)

in th

e C

OP

D c

oho

rt.

report no. 4/11

114

Sun

yer

et

al.

(200

0)

(Sun

yer

et a

l, 20

00)

Bar

celo

na,

Spa

in.

1990

-19

95.

BS

m

eans

: 43

.9

for

case

per

iod,

and

43.

1 fo

r co

ntro

l per

iod.

Tho

se

over

ag

e 35

w

ho

soug

ht

emer

genc

y ro

om

serv

ices

fo

r C

OP

D

exac

erba

tion

durin

g 19

85-1

989

and

died

du

ring

1990

-199

5 w

ere

incl

uded

in

an

alys

is.

Tot

al,

resp

irato

ry,

and

card

iova

scul

ar

deat

hs

wer

e an

alyz

ed

usin

g a

cond

ition

al

logi

stic

re

gres

sion

an

alys

is

with

a

case

-cro

ssov

er

desi

gn,

adju

stin

g fo

r te

mpe

ratu

re,

rela

tive

hum

idity

, an

d in

fluen

za

epid

emic

s.

Bi-d

irect

iona

l co

ntro

l pe

riod

at

7 da

ys w

as u

sed.

Lag

0-2

was

use

d fo

r po

llutio

n ex

posu

re p

erio

d. D

ata

also

str

atifi

ed b

y po

tent

ial

effe

ct m

odifi

ers

(e.g

., ag

e, g

ende

r, s

ever

ity a

nd

num

ber

of e

mer

genc

y ro

om v

isits

, etc

.).

BS

lev

els

wer

e as

soci

ated

with

all

caus

e de

aths

. T

he

asso

ciat

ion

was

st

rong

er

for

resp

irato

ry c

ause

s. O

lder

wom

en,

patie

nts

adm

itted

to

in

tens

ive

care

un

its,

and

patie

nts

with

a

high

er

rate

of

em

erge

ncy

room

vis

its w

ere

at g

reat

er r

isk

of d

eath

s as

soci

ated

with

BS

.

Per

cent

in

crea

se

per

25

µg/

m3

incr

ease

in

3-

day

aver

age

BS

: 14

.2%

(1.

6, 2

8.4)

for

all

caus

es;

9.7%

(-

10.2

, 34

.1)

for

card

iova

scul

ar

deat

hs;

23.2

%

(3.0

, 47.

4) fo

r re

spira

tory

dea

ths.

Sun

yer

and

Bas

agan

a (2

001)

(S

unye

r an

d B

asag

ana,

200

1)

Bar

celo

na,

Spa

in.

1990

- 19

95.

See

Sun

yer

et a

l. (2

000)

(S

unye

r et

al,

2000

) fo

r P

M le

vels

.

The

an

alys

is

asse

ssed

an

y “in

depe

nden

t”

part

icle

ef

fect

s,

afte

r co

ntro

lling

fo

r ga

seou

s po

lluta

nts,

on

a co

hort

of

patie

nts

with

CO

PD

(s

ee t

he s

umm

ary

desc

riptio

n fo

r S

unye

r et

al.

(200

0)

(Sun

yer

et

al,

2000

) fo

r an

alyt

ical

ap

proa

ch).

P

M10

, N

O2,

O

3,

and

CO

w

ere

anal

yzed

.

PM

10,

but

not

gase

ous

pollu

tant

s,

was

as

soci

ated

with

mor

talit

y fo

r al

l ca

uses

. In

th

e tw

o-po

lluta

nt m

odel

s, t

he P

M10

-mor

talit

y as

soci

atio

ns w

ere

not

dim

inis

hed,

whe

reas

th

ose

with

gas

eous

pol

luta

nts

wer

e.

Per

cent

exc

ess

risk

for

all

caus

e m

orta

lity

per

27 µ

g/m

3 (IQ

R)

PM

10

on

the

sam

e-da

y w

as

11%

(0

, 24

). I

n tw

o po

lluta

nt m

odel

s, t

he

PM

10

exce

ss

risks

w

ere

10.5

%,

12.9

%,

and

10.8

% w

ith N

O2,

O3,

an

d C

O, r

espe

ctiv

ely.

report no. 4/11

115

TAB

LE II

– S

HO

RT-

TER

M P

AR

TIC

ULA

TE M

ATT

ER E

XPO

SUR

E A

ND

CA

RD

IOVA

SCU

LAR

HO

SPIT

AL

AD

MIS

SIO

NS

(Der

ived

from

EPA

TA

BLE

8B

-1).

Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

ode

ling

met

hods

: lag

s,

smoo

thin

g, c

o-po

lluta

nts

and

cova

riate

s.

Res

ults

and

Com

men

ts.

PM In

dex,

lag,

per

cent

exc

ess

risk%

(95%

LC

L, U

CL)

APH

EA2

Le

T

ertr

e et

al

. (2

002a

) (L

e T

ertr

e et

al,

2002

a)

Eig

ht-C

ity -

AP

HE

A 2

S

tudy

mea

n (S

D)

PM

10

Bar

celo

na -

1/9

4-12

/96

55.7

(18

.4)

Birm

ingh

am -

3/9

2-12

/94

24.8

(13

.1)

Lond

on -

1/9

2-12

/94

28.4

(12

.3)

Mila

n -

No

PM

10

Net

herla

nds

- 1/

92-9

/95

39.5

(19

.9)

Par

is -

1/9

2-9/

96

PM

13 -

22.

7 (1

0.8)

R

ome

- N

o P

M10

S

tock

holm

- 3

/94-

12/9

6 15

.5 (

7.2)

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

PM

10

and

othe

r co

-pol

luta

nts,

an

d ho

spita

l ad

mis

sion

s fo

r ca

rdia

c ca

uses

in

ei

ght

Eur

opea

n ci

ties

with

a c

om

bine

d po

pula

tion

of

38 m

illio

n. A

utho

rs e

xam

ined

age

fac

tors

and

IH

D

and

st

udie

s al

so

stra

tifie

d by

ag

e us

ing

auto

regr

essi

ve

Poi

sson

m

odel

s co

ntro

lled

for

long

-ter

m t

rend

s, s

easo

n, i

nflu

enza

, ep

ide

mic

s,

and

met

eoro

logy

, as

w

ell

as

conf

ound

ing

by

othe

r po

lluta

nts.

A

sign

ifica

nt

effe

ct

of

PM

10

and

BS

on

ad

mis

sion

s fo

r ca

rdia

c ca

uses

(a

ll ag

es)

an

d ca

rdia

c ca

uses

and

IH

D f

or p

eopl

e o

ver

65 y

ears

was

fou

nd.

The

impa

ct o

f P

M1

0 p

er

unit

of p

ollu

tion

was

hal

f th

at f

ound

in

the

Uni

ted

Sta

tes.

P

M10

di

d n

ot

seem

to

be

co

nfou

nded

by

O3

or

SO

2. T

he e

ffect

was

re

duce

d w

hen

CO

was

inc

orp

orat

ed i

n th

e re

gres

sion

m

odel

an

d el

imin

ated

w

hen

cont

rolli

ng

for

NO

2.

The

re

was

lit

tle

evid

ence

of

an

im

pact

of

pa

rtic

les

on

hosp

ital

adm

issi

ons

for

IHD

fo

r pe

opl

e be

low

65

year

s or

str

oke

for

peop

le o

ver

65

year

s.

The

au

thor

s st

ate

re

sults

w

ere

cons

iste

nt

with

a

role

fo

r tr

affic

ex

hau

st/d

iese

l in

Eur

ope.

For

a 1

0 µ

g/m

3 incr

ease

in P

M10

C

ardi

ac a

dmis

sion

s/al

l age

s 0.

5% (

0.2,

0.8

) C

ardi

ac a

dmis

sion

s/ov

er 6

5 ye

ars

0.7%

(0.

4, 1

.0)

IHD

/ove

r 65

yea

rs

0.8%

(0.

3, 1

.2)

For

car

diac

ad

mis

sion

s fo

r p

eopl

e ov

er 6

5 ye

ars:

All

the

city

-sp

ecifi

c es

timat

es

wer

e po

sitiv

e

with

Lo

ndon

, M

ilan,

an

d S

tock

holm

si

gnifi

cant

at t

he 5

% le

vel.

report no. 4/11

116

HEA

PSS

La

nki

et a

l. (2

006)

(La

nki

et

al,

2006

) H

EA

PS

S

Stu

dy:

Fiv

e

Eur

opea

n ci

ties,

199

2-2

000.

P

M10

; P

NC

(1

/cm

3 ) m

edia

n da

ily

conc

entr

atio

n:

Aug

sbur

g,

Ge

rman

y,

95-

99: 4

3.5;

12,

400

Bar

celo

na,

Spa

in,

92-9

5:

57.4

; 76,

300

Hel

sink

i, F

inla

nd,

93-9

9:

21.0

; 13,

600

R

ome,

Ital

y, 9

8-20

00:

48.5

; 46,

000

S

tock

holm

, S

wed

en,

94-

99: 1

2.5;

11,

800.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

mea

sure

s of

dai

ly c

once

ntra

tion

of P

M10

, P

NC

(a

s a

pro

xy

for

ultr

afin

e pa

rtic

les)

, ot

her

co

-po

lluta

nts

(CO

, N

O2,

O

3),

and

hosp

ital

adm

issi

ons

for

first

AM

I in

fiv

e E

urop

ean

citie

s.

AM

I re

gist

ers

(Aug

sbur

g an

d B

arce

lon

a)

or

hosp

ital

disc

harg

e re

gist

ers

(HD

R)

(Hel

sink

i, R

ome

and

Sto

ckho

lm)

wer

e us

ed.

Dur

ing

the

stud

y pe

riod

no

dire

ct

mea

sure

men

t of

P

NC

w

as

avai

lab

le.

City

-spe

cific

m

odel

s fo

r es

timat

ing

PN

C

from

ot

her

pollu

tant

s an

d m

eteo

rolo

gica

l var

iabl

es w

ere

dev

elop

ed f

or t

he

perio

d w

hen

PN

C w

as m

eas

ured

, an

d ap

plie

d th

en

retr

ospe

ctiv

ely

to

pred

ict

daily

P

NC

co

ncen

trat

ion

s du

ring

the

stud

y pe

riod.

G

AM

m

odel

s w

ere

used

afte

r a

step

wis

e se

lect

ion

of

cova

riate

s.

The

st

artin

g m

odel

in

clud

ed

time

tren

d,

appa

rent

te

mpe

ratu

re,

day

of

wee

k,

holid

ay,

popu

latio

n re

duct

ion,

tem

pera

ture

and

ba

rom

etric

pre

ssur

e. L

ag 0

, la

g 1,

lag

2 a

nd la

g 3

wer

e co

nsid

ered

.

Dur

ing

the

stud

y pe

riod,

26,

854

indi

vidu

als

wer

e h

ospi

talis

ed f

or A

MI.

The

num

ber

of

adm

issi

ons

was

hig

her

in t

he c

entr

es w

here

H

DR

s w

ere

used

co

mpa

red

with

ce

ntre

s w

ith A

MI r

egis

ters

. Whe

n co

nsid

erin

g al

l fiv

e ci

ties,

the

sa

me

day

PN

C a

nd P

M10

wer

e no

t si

gnifi

cant

ly

asso

ciat

ed

to

hosp

italis

atio

n.

Lim

iting

an

alys

es

to

citie

s w

ith H

DR

, th

e sa

me

day

PN

C s

how

ed a

n ex

cess

ris

k of

ho

spita

lisat

ion.

N

o sp

ecifi

c pa

ttern

of

risk

was

see

n co

nsid

erin

g la

gs 1

-3.

S

imila

r as

soci

atio

ns

as

for

PN

C

we

re

foun

d fo

r C

O,

but

no e

xces

s ris

k w

as f

ound

fo

r N

O2

and

O3.

In

the

3 ci

ties

with

HD

R,

the

mos

t co

nsis

tent

as

soci

atio

ns

wer

e sh

ow

n am

ong

fata

l ca

ses

aged

<7

5 ye

ars.

Effe

cts

of m

easu

res

of c

once

ntra

tion

of P

M w

ere

m

ore

pron

ounc

ed f

or f

atal

cas

es a

ged

<7

5 ye

ars.

Per

cent

E

xce

ss

Ris

k of

ho

spita

lisat

ion

for

AM

I (95

% C

I):

Poo

led

effe

cts

(fiv

e ci

ties)

co

mpu

ted

for

10 µ

g/m

3 cha

nge

in

PM

10:

Lag

0: 0

.3%

(-0

.5, 1

.1)

Lag

1: 0

.1%

(-1

.0, 1

.1)

Lag

2: 0

.2%

(-0

.6, 1

.0)

Lag

3: 0

.2%

(-0

.9, 1

.3)

citie

s w

ith H

DR

; lag

0:

Ove

rall:

0.3

% (

-0.6

, 1.2

) N

on-f

atal

, A

ge

<75

: -0

.3%

(-1

.4,

0.8)

F

atal

, Age

<7

5: 3

.1%

(0.

0, 6

.4)

Non

-fat

al,

Ag

e 75

+:

1.2%

(-

0.5,

2.

9)

Fat

al, A

ge 7

5+

: 0.9

% (

-1.5

, 3.

4)

Poo

led

effe

cts

(fiv

e ci

ties)

co

mpu

ted

for

10,0

00/c

m3 c

hang

e in

PN

C:

Lag

0: 0

.5%

(-0

.4, 1

.5)

Lag

1: -

0.3%

(-1

.8, 1

.2)

Lag

2: -

0.1%

(-1

.0, 0

.8)

Lag

3: -

0.2%

(-2

.1, 1

.7)

citie

s w

ith H

DR

; lag

0:

Ove

rall:

1.3

% (

0.0,

2.6

) N

on-f

atal

, A

ge

<75

: 0.

1%

(-2.

5,

1.7)

F

atal

, Age

<7

5: 5

.0%

(0.

0, 1

0.1)

N

on-f

atal

, A

ge

75+

: 3.

2%

(0.8

, 5.

6)

Fat

al, A

ge 7

5+

: 1.6

% (

-2.2

, 5.

5).

report no. 4/11

117

von

Klo

t. (

200

5) (

von

Klo

t et

al

, 20

05)

HE

AP

SS

S

tudy

: F

ive

E

urop

ean

citie

s, 1

992-

200

1.

PM

10;

PN

C (

1/c

m3 )

mea

n da

ily c

once

ntra

tion:

A

ugsb

urg,

G

erm

any,

95

-20

00: 4

4.7;

13

,504

B

arce

lona

, S

pain

, 92

-20

00: 5

2.2;

76

,593

H

elsi

nki,

Fin

land

, 93

-20

00: 2

5.3;

14

,283

R

ome,

Ita

ly,

98-2

001:

51

.1;

49,1

95

Sto

ckho

lm,

Sw

eden

, 94

-20

00: 1

4.6;

12

,553

.

22,0

06 s

urvi

vors

of

a fir

st d

iagn

osis

of

AM

I w

ere

recr

uite

d in

5 E

urop

ean

citie

s an

d fo

llow

ed f

or

hosp

ital

read

mis

sion

s.

Dai

ly

conc

entr

atio

n of

P

M10

and

oth

er

co-p

ollu

tant

s (C

O,

NO

2, O

3)

was

m

easu

red

and

PN

C w

as

est

imat

ed a

s a

pro

xy

for

ultr

afin

e p

artic

les.

Sh

ort-

term

effe

cts

of a

ir po

llutio

n on

ho

spita

l re

adm

issi

ons

for

AM

I, an

gina

pec

toris

, an

d ca

rdia

c ca

uses

(m

yoca

rdia

l in

farc

tion,

ang

ina

pect

oris

, d

ysrh

ythm

ia,

or h

eart

fa

ilure

) w

ere

st

udie

d in

ci

ty-s

peci

fic

Poi

sson

re

gres

sion

an

alys

es

with

su

bseq

uent

po

olin

g.

Pot

entia

l co

nfo

unde

rs

wer

e se

lect

ed

thro

ugh

pena

lized

reg

ress

ion

splin

es o

f tr

end

(to

cont

rol

for

long

-ter

m t

rend

s, s

easo

nalit

y, a

nd c

han

ges

in

the

base

line

rate

) an

d m

eteo

rolo

gy

(dai

ly

tem

pera

ture

, re

lativ

e hu

mid

ity,

air

pres

sure

, an

d th

e di

ffere

nce

bet

wee

n cu

rren

t da

y te

mp

erat

ure

and

the

mea

n te

mpe

ratu

re o

f th

e pr

evio

us 3

da

ys),

as

w

ell

as

indi

cato

rs

of

day

of

wee

k,

vaca

tion

perio

ds,

or h

olid

ays.

Tre

nd a

nd o

ne

tem

pera

ture

ter

m r

emai

ned

in t

he m

odel

. La

g 0,

1,

2,

3

wer

e co

nsid

ered

. G

iven

th

e re

sults

ob

tain

ed,

the

ef

fect

s of

la

g 0

air

pollu

tion

conc

entr

atio

ns

wer

e sh

ow

n.

Dur

ing

follo

w-u

p,

6,65

5 ca

rdia

c re

adm

issi

ons

wer

e ob

serv

ed.

C

ardi

ac

read

mis

sion

s in

crea

sed

in

asso

ciat

ion

with

sa

me-

day

conc

entr

atio

ns

of

PM

10

and

P

NC

. N

o a

ssoc

iatio

ns

wer

e fo

und

cons

ider

ing

lags

1

-3.

Effe

cts

of

sim

ilar

stre

ngth

wer

e ob

serv

ed f

or C

O,

NO

2 an

d O

3.

Poo

led

effe

cts

com

pute

d fo

r 10

µ

g/m

3 cha

nge

in P

M10

: A

MI:

2.6%

(-0

.5, 5

.8)

Ang

ina

pect

oris

: 0.8

% (

-1.4

, 3.

2)

Car

diac

re

adm

issi

on:

2.1

%

(0.4

, 3.

9)

Poo

led

effe

cts

com

pute

d fo

r 10

,000

/cm

3 ch

ange

in P

NC

: A

MI:

3.9%

(-0

.2, 8

.2)

Ang

ina

pect

oris

: 2.0

% (

-0.8

, 4.

8)

Car

diac

re

adm

issi

on:

2.6

%

(0.5

, 4.

8).

report no. 4/11

118

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Atk

inso

n et

al

. (1

999b

) (A

tkin

son

et a

l, 19

99b)

G

reat

er L

ondo

n, E

ngla

nd

1992

-199

4.

Pol

luta

nt:

me

an,

med

ian,

90

-10

perc

entil

e ra

nge:

P

M10

: 28.

5, 2

4.8

, 30.

7 B

S: 1

2.7,

10.

8, 1

6.1.

Dai

ly e

mer

genc

y ho

spita

l ad

mis

sion

s fo

r to

tal

CV

D

(IC

D9:

39

0-45

9),

and

IHD

(I

CD

9:

410-

414)

, fo

r al

l a

ges,

for

per

sons

les

s th

an 6

5, a

nd

for

pers

ons

65

and

olde

r.

Mea

n da

ily

adm

issi

ons

for

CV

D:

172.

5 a

ll ag

es,

54.5

<65

, 11

7.8

≥ 65

; fo

r IH

D:

24.5

<

65,

37.6

≥

65.

Cov

aria

tes:

N

O2,

O

3,

SO

2,

CO

, te

mpe

ratu

re,

rela

tive

hum

idity

. P

oiss

on

regr

essi

on

usin

g A

PH

EA

met

hodo

logy

; si

ne a

nd c

osin

e fu

nctio

ns

for

seas

onal

co

ntro

l; da

y of

w

eek

dum

my

varia

bles

. La

gs

0-3,

as

wel

l as

cor

resp

ond

ing

mul

ti-da

y av

erag

es

endi

ng

on

lag

0,

wer

e

cons

ider

ed.

In s

ingl

e-po

lluta

nt m

odel

s, b

oth

PM

met

rics

sho

wed

pos

itive

ass

ocia

tion

s w

ith b

oth

CV

D

and

IHD

adm

issi

ons

acro

ss a

ge g

roup

s. I

n T

wo-

po

lluta

nt

mod

els,

th

e B

S e

ffect

, b

ut

not

the

PM

10

effe

ct,

was

ro

bust

. N

o qu

antit

ativ

e re

sults

pr

ovid

ed

for

two-

pollu

tant

m

odel

s.

Thi

s st

udy

does

no

t su

ppor

t a

PM

10 e

ffect

ind

epen

dent

of

co-

pollu

tant

s.

Effe

cts

com

put

ed

for

50

µg/

m3

PM

10 a

nd 2

5 µ

g/m

3 BS

P

M10

(la

g 0)

: A

ll ag

es:

CV

D: 3

.2%

(0.

9, 5

.5)

0- 6

4 ye

ars:

C

VD

: 5.6

% (

2.0,

9.4

) IH

D: 6

.8%

(1.

3, 1

2.7)

65

+ y

ears

: C

VD

: 2.5

% (

-0.2

, 5.3

) IH

D: 5

.0%

(0.

8, 9

.3)

BS

(la

g 0)

: A

ll ag

es:

CV

D: 2

.95

% (

1.00

, 4.9

4)

0-64

yea

rs:

CV

D: 3

.12

% (

0.05

, 6.2

9)

IHD

: 2.7

8%

(-

1.88

, 7.6

3)

65+

yea

rs:

CV

D: 4

.24

% (

1.89

, 6.6

4)

IHD

(la

g 3)

: 4.5

7% (

0.86

, 8.4

2).

Pre

scot

t et

al

. (1

998)

(P

resc

ott e

t al,

1998

) E

dinb

urgh

, Sco

tland

19

81-1

995

(BS

and

SO

2)

1992

-199

5 (P

M10

, N

O2,

O

3, C

O)

Mea

ns f

or l

ong

and

shor

t se

ries:

B

S: 1

2.3,

8.7

P

M10

: NA

, 20.

7.

Dai

ly e

mer

genc

y ho

spita

l ad

mis

sion

s fo

r C

VD

(I

CD

9: 4

10-4

14,

426

-429

, 4

34-4

40)

for

pers

ons

less

tha

n 65

yea

rs a

nd f

or p

erso

ns 6

5 or

old

er.

Sep

arat

e an

alys

es

pres

ente

d fo

r lo

ng

(198

1-19

95)

and

shor

t (1

992-

1995

) se

ries.

M

ean

hosp

ital

adm

issi

ons

for

lon

g an

d sh

ort

serie

s:

<65

, 3.

5, 3

.4;

65+

, 8.

0, 8

.7.

Cov

aria

tes:

SO

2,

NO

2, O

3, C

O,

win

d sp

eed,

tem

pera

ture

, ra

infa

ll.

PM

10

mea

sure

d by

T

EO

M.

Poi

sson

lo

g-li

near

re

gres

sion

; tr

end

and

sea

sons

co

ntro

lled

by

mon

thly

du

mm

y va

riabl

es

over

en

tire

serie

s;

day

of

we

ek

dum

my

varia

bles

; m

in

daily

te

mpe

ratu

re

mod

eled

us

ing

octil

e du

mm

ies.

P

ollu

tant

s e

xpre

ssed

as

cum

ulat

ive

lag

1-3

day

mov

ing

avg.

In

long

se

ries,

ne

ither

B

S

nor

NO

2

we

re

asso

ciat

ed w

ith C

VD

adm

issi

ons

in e

ither

ag

e gr

oup.

In

the

shor

t se

ries,

onl

y 3-

day

mov

ing

aver

age

P

M10

w

as

posi

tivel

y an

d si

gnifi

cant

ly

asso

ciat

ed

with

C

VD

ad

mis

sion

s in

sin

gle-

pol

luta

nt m

odel

s, a

nd

only

for

per

sons

65

or o

lde

r. B

S,

SO

2, a

nd

CO

al

so

sho

wed

po

sitiv

e

asso

ciat

ion

s in

th

is s

ubse

t, b

ut w

ere

not

sign

ifica

nt a

t th

e 0.

05 le

vel.

The

PM

10 e

ffect

rem

aine

d la

rgel

y un

chan

ged

whe

n al

l ot

her

pollu

tant

s w

ere

adde

d to

the

mod

el,

how

ever

qua

ntita

tive

resu

lts w

ere

not

give

n. R

esul

ts a

ppea

r to

sh

ow

an

effe

ct o

f P

M10

ind

epen

dent

of

co-

pollu

tant

s.

Per

cent

Exc

ess

Ris

k (9

5%

CI)

: E

ffect

s co

mp

uted

fo

r 50

µ

g/m

3 ch

ange

in

P

M10

an

d 25

µ

g/m

3 ch

ange

in B

S.

Long

ser

ies:

B

S, l

ag

1-3:

<

65: -

0.5%

(-5

.4, 4

.6)

65+

: -0.

5% (

-3.8

, 2.9

) S

hort

ser

ies:

B

S, l

ag

1-3:

<

65: -

9.5%

(-2

4.6,

8.0

) 65

+: 5

.8%

(-4

.9, 1

7.8)

P

M10

, lag

1-3

: <

65: 2

.0%

(-

12.

5, 1

9.0)

65

+: 1

2.4

% (

4.6,

20.

9).

report no. 4/11

119

Won

g et

al.

(200

2) (

Won

g et

al,

2002

)

Lond

on, U

K, 1

992-

1994

. m

ean

daily

con

cent

ratio

n of

PM

10: 2

8.5.

The

pr

esen

t st

udy

exa

min

ed

the

rela

tion

betw

een

PM

10

and

othe

r co

-pol

luta

nts

(NO

2,

SO

2 an

d O

3),

and

daily

ad

mis

sion

for

car

diac

di

seas

es (

ICD

9: 3

90-4

29)

and

IHD

(IC

D9

: 41

0-41

4) i

n th

e ci

ty o

f Lo

ndon

. T

he s

ame

anal

yses

w

ere

perf

orm

ed

for

the

city

of

H

ong

Kon

g (f

indi

ngs

not

sho

wn

in

the

pres

ent

repo

rt).

P

oiss

on r

egre

ssio

n w

as u

sed

adju

stin

g fo

r no

n-pa

ram

etric

sm

ooth

fu

nctio

ns

of

time,

te

mpe

ratu

re,

hum

idity

, in

fluen

za e

pide

mic

s, d

ay

of t

he w

eek,

hol

iday

s an

d se

ason

s. A

n a

prio

ri la

g 0-

1 w

as u

sed.

Est

imat

es

for

the

best

sin

gle

day

lag

(0,

1,

2,

3)

wer

e al

so

sho

wn.

T

he

exce

ss r

isks

of

hosp

italis

atio

n w

ere

also

sho

wn

afte

r m

utua

l ad

just

men

t fo

r ea

ch

sing

le

co-

pollu

tant

.

PM

10

sign

ifica

ntly

in

crea

sed

the

hosp

italis

atio

n

for

card

iac

dise

ases

an

d IH

D,

part

icul

arly

in c

old

seas

ons,

eve

n af

ter

furt

her

adju

stm

ent

for

O3.

Whe

n ad

just

ing

for

NO

2 an

d S

O2,

no

exc

ess

adm

issi

ons

for

card

iac

dise

ases

wer

e fo

und

with

PM

10.

SO

2 an

d N

O2

incr

ease

d an

d

O3

decr

ease

d ca

rdia

c ho

spita

l adm

issi

on.

R

emar

kabl

y si

mila

r as

soci

atio

ns w

ere

fou

nd

in H

ong

Kon

g.

Per

cent

e

xces

s ris

k fo

r an

in

crem

ent o

f PM

10 b

y 10

µg/

m3 :

Car

diac

dis

ease

s, a

ll ag

es,

lag

0-1:

0.

8% (

0.3,

1.4

) W

arm

sea

son

s: 0

.1%

(-0

.7,

1.0)

C

old

seas

ons:

1.2

% (

0.5,

2.0

) A

djus

ted

for

NO

2: 0

.2%

(-0

.6, 1

.0)

Adj

uste

d fo

r O

3: 0

.8%

(0.

3, 1

.3)

Adj

uste

d fo

r S

O2:

-0

.2%

(-

1.1

, 0.

4)

IHD

, all

ages

, la

g 0-

1:

0.9%

(0.

1, 1

.6)

War

m s

easo

ns:

0.1

% (

-1.1

, 1.

4)

Col

d se

ason

s: 1

.3%

(0.

3, 2

.3)

Wor

dley

et

al

. (1

997)

(W

ordl

ey e

t al,

1997

) B

irmin

gham

, U

K,

4/1/

92-

3/31

/94.

P

M10

mea

n, m

in,

ma

x: 2

6,

3, 1

31.

Dai

ly h

osp

ital

adm

issi

ons

for

IHD

(IC

D9

: 41

0-42

9)

for

all

ages

. M

ean

ho

spita

lizat

ions

: 25

.6/d

ay.

Cov

aria

tes:

tem

pera

ture

and

rel

ativ

e hu

mid

ity.

Lin

ear

regr

essi

on

was

u

sed

af

ter

adju

stm

ent

for

day

of w

eek

and

mon

thly

dum

my

varia

bles

, lin

ear

tren

d te

rm.

Lags

of

0-

3 co

nsid

ered

, as

wel

l as

the

mea

n of

lags

0-2

.

No

stat

istic

ally

si

gnifi

cant

ef

fect

s w

ere

ob

serv

ed f

or P

M10

on

IHD

adm

issi

ons

for

any

lag.

Not

e th

at P

M1

0 w

as

asso

ciat

ed w

ith

resp

irato

ry

adm

issi

ons

an

d

with

ca

rdio

vasc

ular

mor

talit

y in

the

sam

e st

udy

(res

ults

not

sho

wn

here

).

Per

cent

ch

ange

pe

r 50

µ

g/m

3 ch

ange

PM

10 I

HD

adm

issi

on

s:

lag

0: 1

.4%

(-4

.4, 7

.2)

lag

1:-1

.3%

(-7

.1, 4

.4).

report no. 4/11

120

And

erso

n et

al

. (2

001)

(A

nder

son

et a

l, 20

01)

W

est M

idla

nd,

Eng

land

(O

ctob

er 1

994-

Dec

embe

r 19

96)

Pop

ulat

ion:

2.3

mill

ion

P

M10

mea

n: 2

3.3

PM

2.5

mea

n: 1

4.5

PM

10-2

.5: 9

.0.

Car

diov

ascu

lar

hosp

ital

adm

issi

ons

(IC

D9:

390

-45

9)

rela

ted

to

PM

10,

PM

2.5,

P

M10

-2.5,

BS

, su

lfate

, N

O2,

O3,

SO

2, C

O.

GLM

reg

ress

ion

with

qu

asi-

likel

ihoo

d ap

proa

ch,

cont

rolli

ng

for

seas

onal

pa

ttern

s,

tem

pera

ture

, hu

mid

ity,

influ

enza

epi

sode

s, d

ay o

f th

e w

eek.

Adj

uste

d fo

r re

sidu

al

seria

l co

rrel

atio

n an

d

over

-di

sper

sion

. C

ardi

ac

dise

ase

(IC

D9:

39

0-42

9),

IHD

(co

nsid

ered

for

age

≥65

yea

rs,

ICD

9:

410-

414)

and

str

oke

(con

side

red

for

age ≥6

5 ye

ars

ICD

9:

430-

438)

w

ere

co

nsid

ere

d as

su

bdia

gnos

es.

Hos

pita

l ad

mis

sion

s (a

ll a

ges)

fo

r C

VD

, ca

rdia

c di

seas

e an

d IH

D

wer

e no

t as

soci

ated

w

ith

any

cons

ider

ed

pollu

tant

. A

n in

vers

e as

soci

atio

n b

etw

een

P

M10

-2.5

and

adm

issi

on

for

stro

ke w

as

foun

d. T

he

only

sig

nific

ant

seas

onal

int

erac

tion

was

for

B

S,

whi

ch s

how

ed

a po

sitiv

e as

soci

atio

n i

n

the

war

m s

easo

n.

CV

D h

ospi

tal

adm

issi

on;

lag

0-1;

P

M10

In

crem

ent

10-9

0%

(11.

4-38

.3 µ

g/m

3 ):

All

CV

D: -

0.6

(-2.

5, 1

.3)

Car

diac

: 0.3

(-1

.8, 2

.4)

IHD

: 2.1

(-2

.0, 6

.3)

Str

oke:

-3.

3 (-

7.9,

1.4

) P

M2.

5 (6

.0-2

5.8

µg/

m3 )

All

CV

D: -

0.5

(-2.

6, 1

.6)

Car

diac

: -0.

4 (-

2.8,

2.2

) IH

D: -

0.3

(-4.

5, 4

.2)

Str

oke:

-1.

6 (-

6.6,

3.6

) P

M10

-2.5 (

4.1-

15.2

µg/

m3 )

All

CV

D: -

0.7

(-3.

7, 2

.3)

Car

diac

: -0.

9 (-

4.3,

2.7

) IH

D: 1

.1 (

-4.1

, 6.6

) S

trok

e: -

8.2

(-13

.9, -

2.2)

B

S (

5.1-

23.6

µg/

m3 )

All

CV

D: 1

.0 (

-1.0

, 3.1

) C

ardi

ac: 1

.7 (

-0.6

, 3.9

) IH

D: 2

.0 (

-2.3

, 6.4

) S

trok

e: -

2.7

(-7.

6, -

2.4)

.

N

OR

WA

Y

Man

nsak

er

(200

4)

(Man

nsak

er e

t al,

2004

)

Tro

ndhe

im,

Nor

way

, 19

93-2

001.

m

edia

n da

ily

conc

entr

atio

n: P

M10

39.

3;

PM

2.5

13.2

.

Thi

s st

udy

com

pare

d th

e m

ean

daily

num

ber

of

adm

issi

ons

for

CV

D t

o th

e S

t. O

lav

Uni

vers

ity

hosp

ital

in t

he

city

of

Tro

ndh

eim

, on

da

ys w

ith

rela

tivel

y lo

w a

nd h

igh

leve

ls o

f P

M10

, P

M2,

5,

and

othe

r co

-pol

luta

nts,

in

clud

ing

NO

, N

O2,

S

O2,

O3.

A t

ime

serie

s an

alys

is w

as c

arrie

d ou

t to

se

e ho

w

day-

to-d

ay

varia

tion

s in

co

ncen

trat

ion

s of

air

pollu

tant

s co

rrel

ated

with

th

e nu

mbe

r of

ad

mis

sion

s fo

r ca

rdio

vasc

ular

di

seas

e.

Tim

e se

ries

anal

ysis

d

id

not

sho

w

an

y st

atis

tical

ly

sign

ifica

nt

corr

elat

ion

betw

een

da

y-to

-day

va

riatio

ns

in

air

pollu

tion

and

hosp

ital

adm

issi

ons

for

card

iova

scul

ar

dise

ase.

T

he m

ean

daily

num

ber

of h

ospi

taliz

atio

ns

wa

s fo

und

to b

e si

gnifi

cant

ly h

ighe

r on

da

ys

with

hig

h le

vels

of

NO

and

NO

2, b

ut n

ot w

ith

othe

r po

lluta

nts.

No

risk

sho

wn

.

report no. 4/11

121

GER

MA

NY

W

ichm

ann

et

al

(200

4)

(Wic

hman

n, 2

004)

R

hine

-Ruh

r ar

ea,

Ger

man

y,

198

5,

sing

le

epis

ode.

TS

P d

urin

g th

e ep

isod

e in

R

hine

-Ruh

r ar

ea: ~

600

.

In

Janu

ary

1985

an

ex

ten

ded

smog

ep

isod

e oc

curr

ed i

n C

entr

al E

urop

e t

oget

her

with

ver

y lo

w t

empe

ratu

res.

Thi

s pa

per

revi

ew

s th

e he

alth

ef

fect

s, i

nclu

din

g C

VD

adm

issi

on,

inve

stig

ated

du

ring

the

smog

pe

riod

and

a co

ntro

l pe

riod

befo

re a

nd a

fter

the

smog

epi

sode

. T

he R

hine

-Ru

hr a

rea

(Wes

tern

Ger

man

y) w

as

affe

cted

for

5 d

ays

with

ma

xim

um c

once

ntra

tion

of

TS

P

of

600

µ

g/m

3 (2

4 h

aver

age

s).

In

Aug

sbur

g (S

outh

ern

Ger

man

y)

the

smog

ep

isod

e w

as l

ess

seve

re (

100

µg/

m3 T

SP

, 24

h

aver

ages

).

Rhi

ne-R

uhr

hos

pita

l ad

mis

sion

s in

crea

sed

by 5

7% f

or c

ereb

ral

circ

ulat

ion

failu

re,

by

30%

for

cor

ona

ry i

nsuf

ficie

ncy,

by

19%

for

C

VD

, by

14

% f

or h

eart

ins

uffic

ienc

y an

d by

10

% fo

r A

MI.

No

risk

sho

wn

.

Pet

ers

et

al

(200

4)

(Pet

ers

et a

l, 20

04)

Aug

sbur

g,

Ger

man

y,

1999

-200

1.

No

info

rmat

ion

on P

M.

Thi

s is

a

case

-cro

ssov

er

stud

y in

w

hich

69

1 ca

ses

of

non

-fat

al

myo

card

ial

AM

I w

ere

iden

tifie

d in

th

e A

ugsb

urg

Myo

card

ial

Infa

rctio

n R

egis

try

in A

ugsb

urg,

bet

wee

n F

ebru

ary

1999

an

d Ju

ly 2

001.

Cas

es p

rovi

ded

info

rmat

ion

on

fact

ors

that

may

hav

e tr

igge

red

the

myo

card

ial

infa

rctio

n. D

ata

on s

ubje

cts'

act

iviti

es d

urin

g th

e fo

ur

days

pr

eced

ing

the

onse

t of

sy

mpt

oms

wer

e c

olle

cte

d w

ith t

he

use

of p

atie

nt d

iarie

s.

Con

ditio

nal

logi

stic

re

gres

sion

m

odel

s w

ere

used

to

es

timat

e th

e as

soci

atio

n be

twee

n tr

ansi

ent

exp

osu

re t

o tr

affic

and

the

ris

k of

AM

I. T

he “

cont

rol p

erio

d” o

f e

xpo

sure

was

def

ined

as

an e

xpos

ure

to t

raffi

c by

the

sam

e su

bjec

t 24

to

71 h

ours

bef

ore

the

hour

of

the

onse

t of

the

A

MI.

Onl

y su

bjec

ts

for

who

m

ther

e

wer

e di

scor

dant

se

ts

of

data

on

ex

posu

re

wer

e in

clud

ed in

the

ana

lyse

s.

An

asso

ciat

ion

was

fo

und

betw

een

expo

sure

to

traf

fic a

nd t

he o

nset

of

an A

MI

with

in o

ne h

our

afte

rwar

d (O

R=

2.92

; 95

%

CI:

2.22

-3.8

3).

The

tim

e th

e su

bjec

ts s

pen

t in

ca

rs,

on

publ

ic

tran

spor

tatio

n,

or

on

mot

orcy

cles

or

bi

cycl

es

wa

s co

nsis

tent

ly

linke

d w

ith a

n in

crea

sed

risk

of A

MI.

No

data

on

PM

report no. 4/11

122

FRA

NC

E

Eils

tein

et

al

(2

004)

(E

ilste

in e

t al,

2004

)

Nin

e F

renc

h ci

ties,

199

5-19

99.

No

data

di

strib

utio

n w

as

repo

rted

.

Thi

s st

udy

exa

min

ed t

he s

hort

ter

m e

ffect

s of

P

M10

, B

S

an

d ot

her

co-p

ollu

tant

s (C

O,

NO

2,

SO

2,

O3)

on

m

orta

lity

and

hosp

italis

atio

n fo

r ca

rdio

vasc

ular

(a

nd

resp

irato

ry)

diso

rder

s in

ni

ne F

renc

h ci

ties

(Bor

dea

ux,

Le H

avre

, Li

lle,

Lyon

, M

arse

ille,

Par

is,

Rou

en,

Str

asbo

urg

and

Tou

lous

e)

of

the

Sur

veill

ance

A

ir et

S

ante

pr

ogra

m.

The

an

alys

is

asse

ssed

th

e ci

ty-

spec

ific

and

com

bine

d as

soci

atio

ns w

ith v

ario

us

pollu

tant

s us

ing

Poi

sson

GA

M,

afte

r a

djus

ting

for

tren

ds i

n se

ason

s, d

ay o

f w

eek,

hol

iday

s,

influ

enza

ep

idem

ics,

tem

pera

ture

and

hu

mid

ity.

A c

ombi

ned

RR

was

cal

cula

ted

for

all t

he c

ities

. La

g 0-

1 an

d la

g 0-

5 w

ere

used

.

Nei

ther

P

M10

no

r B

S

show

ed

sign

ifica

nt

exce

ss a

dmis

sion

for

CV

D.

CV

D a

dmis

sio

n, e

ffect

s co

mpu

ted

for

10 µ

g/m

3 cha

nge

in e

xpo

sitio

n:

Lag

0-1

PM

10; a

ge 1

5-64

: 0.0

% N

S

PM

10; a

ge 6

5+

: 0.1

% N

S

Lag

0-5

PM

10; a

ge 1

5-64

: 0.0

% N

S

PM

10; a

ge 6

5+

: 0.7

% N

S

Lag

0-1

BS

; age

15-

64: 0

.4%

NS

B

S; a

ge 6

5+:

0.3%

NS

La

g 0-

5 B

S; a

ge 1

5-64

: 0.6

% N

S

BS

; age

65+

: 0.

3% N

S

ITA

LY

B

igge

ri et

al

. (2

005)

(B

igge

ri et

al,

2005

) E

ight

ci

ties

of

Nor

th,

Cen

tre

and

So

uth

of It

aly

1990

-199

9.

PM

10

me

an

daily

co

ncen

trat

ion:

T

urin

, 91-

94: 7

7.6

Tur

in, 9

5-98

: 63.

8 M

ilan,

90-

94: 6

1.8

Mila

n, 9

5-97

: 45.

2 V

eron

a, 9

5-99

: 36.

5 R

aven

na, 9

1-95

: 59.

1 B

olog

na, 9

6-9

8: 4

1.2

Flo

renc

e, 9

6-98

: 40.

3 R

ome,

92-

94: 6

9.7

Pal

erm

o, 9

7-99

: 42.

9.

Met

a-an

alys

is

of

shor

t-te

rm

effe

cts

of

air

pollu

tion

on

mor

talit

y an

d ho

spita

l ad

mis

sion

(c

ardi

ac

cau

ses

– IC

D9:

39

0-45

9-,

and

resp

irato

ry c

ause

s) i

n ei

ght

Italia

n ci

ties

from

19

90 t

o 19

99.

Dai

ly c

once

ntra

tions

of

pollu

tant

s w

ere

colle

cte

d. A

gen

eral

ized

lin

ear

mod

el w

as

used

afte

r ad

just

men

t fo

r a

ge,

day

of t

he w

eek,

ho

liday

s,

influ

enza

ep

ide

mic

s,

met

eoro

logi

cal

varia

bles

, an

d s

easo

nalit

y p

atte

rn w

as

fitte

d fo

r P

M10

and

oth

er

co-p

ollu

tant

(S

O2,

NO

2, C

O,

and

O3)

. C

ity-s

peci

fic a

nd f

ixed

- an

d ra

ndom

-effe

cts

pool

ed e

stim

ate

s w

ere

sho

wn.

La

g 0-

3 w

as

use

d fo

r ho

spita

l adm

issi

on.

A s

igni

fican

t di

rect

ass

ocia

tion

was

fou

nd

betw

een

PM

10

and

card

iac

hosp

ital

adm

issi

on.

The

ot

her

cons

ider

ed

co-

pollu

tant

s, w

ith t

he e

xcep

tion

of O

3, s

how

ed

stro

nger

as

soci

atio

ns.

Th

e ex

cess

ris

ks

wer

e m

odifi

ed b

y de

priv

atio

n sc

ore

and

by

the

NO

2/P

M10

rat

io.

Car

diac

ho

spita

l ad

mis

sion

, ef

fect

s co

mpu

ted

for

10

µg/

m3

chan

ge in

PM

10 (

lag

0-3)

: F

ixed

-effe

cts:

0.7

7% (

0.40

, 1.

15)

Ran

dom

-effe

cts:

0.

82%

(0

.32,

1.

32).

report no. 4/11

123

D’Ip

polit

i (20

03)

(D

'Ippo

liti

et a

l, 20

03)

Rom

e, It

aly,

199

5-19

97.

TS

P

mea

n da

ily

conc

entr

atio

n

from

5

mon

itors

(S

D):

66

.9

(19.

7).

A

case

-cro

ssov

er

anal

ysis

w

as

cond

uct

ed

to

eval

uate

the

rel

atio

n be

twee

n T

SP

and

oth

er

co-p

ollu

tant

s (S

O2,

C

O,

NO

2)

and

hosp

ital

adm

issi

on

for

a fir

st

epis

ode

of

acut

e A

MI

(IC

D9:

410

). I

n th

e pe

riod

of o

bser

vatio

n 6,

531

subj

ects

res

idin

g in

Rom

e w

ere

hosp

italiz

ed f

or

AM

I.

A

time-

stra

tifie

d ca

se-c

ross

over

de

sign

w

as

cons

ider

ed,

usin

g as

con

trol

day

s th

e sa

me

day

of

the

wee

k as

th

e m

yoca

rdia

l in

farc

tion

occu

rred

, in

ot

her

wee

ks

of

the

mon

th.

OR

s w

ere

der

ived

by

cond

ition

al

logi

stic

reg

ress

ion

mod

els

afte

r al

low

ance

fo

r te

mpe

ratu

re

and

hum

idity

. A

n

a pr

iori

lag

0-2

wa

s us

ed.

Est

imat

es f

or l

ags

0, 1

, 2,

3,

and

4 w

ere

also

sh

ow

n.

Pos

itive

as

soci

atio

ns

wer

e

foun

d fo

r to

tal

susp

ende

d p

artic

ulat

e,

NO

2 an

d C

O.

The

st

rong

est

and

m

ost

cons

iste

nt

effe

ct

wa

s fo

und

for

TS

P,

in p

artic

ular

dur

ing

the

war

m

seas

on,

amon

g th

e el

derly

an

d am

ong

peop

le w

ith h

ear

t con

duct

ion

dis

turb

ance

s.

Per

cent

exc

ess

ris

k (9

5% C

I) f

or

an in

crem

ent o

f TS

P b

y 10

µg/

m3 ;

Lag

0: 2

.3 (

0.4,

4.2

) La

g 1:

1.5

(-0

.4, 3

.4)

Lag

2: 1

.7 (

-0.1

, 3.5

) La

g 3:

-0.

9 (-

2.6,

0.3

La

g 4:

0.1

(-1

.3, 1

.6)

Lag

0-2:

O

vera

ll: 2

.8 (

0.5,

5.2

)

Mal

es: 2

.3 (

-0.5

, 5.1

) F

emal

es: 3

.9 (

0.0,

8.0

) A

ge 1

8-64

: 1.3

(-2

.2, 4

.8)

Age

65-

74: 3

.2 (

-1.0

, 7.6

) A

ge 7

5+: 4

.6 (

0.5,

8.9

) C

old

perio

d: 1

.8 (

-1.1

, 4.7

) W

arm

per

iod:

4.6

(0.

8, 8

.7).

S

tafo

ggia

et

al

. (2

005)

(S

tafo

ggia

et

al, 2

005)

R

ome,

Ital

y, 1

998-

2000

. P

M10

; P

NC

(n

o/cm

3 ) m

ean

daily

co

ncen

trat

ion:

52

.1;

51,6

69,

resp

ectiv

ely.

The

stu

dy e

xam

ined

the

rel

atio

nshi

p be

twee

n P

M10

, P

NC

and

oth

er c

o-po

lluta

nts

(CO

, N

O2,

S

O2

and

O3)

and

cor

onar

y ev

ents

for

res

iden

ts

in

Rom

e,

cons

ider

ing

bot

h ou

t-of

-hos

pita

l de

aths

an

d ho

spita

lisat

ions

. G

ener

alis

ed

addi

tive

mod

els

adju

sted

by

te

mpo

ral

tren

d,

tem

pera

ture

, hu

mid

ity,

day

of w

eek,

ho

liday

s,

and

popu

latio

n re

duct

ion

in

sum

mer

m

onth

s w

ere

used

. La

gs

0,

1,

0-1

and

0-4

wer

e co

nsid

ered

.

A

sign

ifica

nt

exce

ss

risk

of

hosp

ital

adm

issi

on

for

coro

nary

ev

ents

w

as

foun

d w

ith

sam

e-d

ay

PN

C

and

C

O.

No

asso

ciat

ion

was

fou

nd w

ith s

ame-

day

PM

10,

NO

2, S

O2

and

O3.

T

he a

ssoc

iatio

ns w

ith P

NC

and

CO

wer

e st

rong

er fo

r el

derly

sub

ject

s.

Per

cent

exc

ess

ris

k (9

5% C

I) f

or

an

incr

emen

t of

P

M10

by

29

.7

µg/

m3 (

IQR

)

Lag

0: 0

.9 (

-2.3

, 4.2

) La

g 1:

-1.

2 (-

4.4,

2.2

) La

g 0-

1: 0

.3 (

-3.2

, 4.0

) La

g 0-

4: -

2.0

(-6.

5, 2

.6)

Lag

0; a

ge 3

5-65

: -2.

5 (-

7.2,

2.4

) La

g 0;

age

65-

74: 1

.5 (

-4.2

, 7.6

) La

g 0;

age

75

+: 3

.2 (

-2.4

, 9.2

) P

erce

nt e

xce

ss r

isk

(95%

CI)

for

an

inc

rem

ent

of P

NC

by

28,0

01

no/c

m3 (

IQR

)

Lag

0: 4

.0 (

0.1,

8.1

) La

g 1:

0.4

(-3

.5, 4

.4)

Lag

0-1:

2.8

(-1

.6, 7

.4)

Lag

0-4:

0.2

(-4

.7, 5

.5)

Lag

0; a

ge 3

5-65

: 2.4

(-3

.5, 8

.6)

Lag

0; a

ge 6

5-74

: -0.

2 (-

6.9,

6.9

) La

g 0;

age

75

+: 9

.0 (

2.2,

16

.2).

report no. 4/11

124

SPA

IN

D

íaz

et a

l. (1

999

) (D

iaz

et

al, 1

999)

M

adrid

, Spa

in,

1994

-199

6 T

SP

by

beta

atte

nuat

ion.

S

umm

ary

stat

istic

s no

t gi

ven.

Dai

ly

emer

genc

y ho

spita

l ad

mis

sion

s fo

r al

l ca

rdio

vasc

ular

cau

ses

(IC

D9:

390

-459

) fo

r th

e G

rego

rio M

aran

on U

nive

rsity

Tea

chin

g H

ospi

tal.

Mea

n ad

mis

sion

s:

9.8/

day.

C

ovar

iate

s:

SO

2,

NO

2,

O3,

te

mpe

ratu

re,

pres

sure

, re

lativ

e hu

mid

ity,

exc

ess

sunl

ight

. B

ox-

Jenk

ins

time-

serie

s m

etho

ds

wer

e us

ed

to

rem

ove

auto

corr

elat

ions

, fo

llow

ed b

y cr

oss-

cor

rela

tion

an

alys

is;

sine

and

cos

ine

term

s fo

r se

ason

ality

; de

tails

unc

lear

.

No

sign

ifica

nt

effe

cts

of

TS

P

on

CV

D

repo

rted

. N

o qu

antit

ativ

e re

sults

pre

sent

ed

for

PM

.

Llor

ca

et

al.

(200

5)

(Llo

rca

et a

l, 20

05)

T

orre

lave

ga,

Spa

in,

1992

-199

5.

No

data

di

strib

utio

n w

as

repo

rted

.

Thi

s st

udy

anal

ysed

the

rel

atio

ns b

etw

een

TS

P

and

othe

r co

-pol

luta

nts

(NO

, N

O2,

S

O2

and

hydr

ogen

sul

fide)

, an

d em

erge

ncy

adm

issi

ons

for

card

iac

dise

ase

(IC

D9:

39

0-4

59)

in

Tor

rela

vega

(6

0,00

0 in

hab

itant

s).

RR

s w

ere

estim

ated

fo

r ea

ch

pollu

tant

by

P

oiss

on

regr

essi

on a

djus

ted

for

influ

enza

, da

y of

wee

k,

win

d sp

eed,

win

d an

d te

mpe

ratu

re.

Lag

0 w

as

appa

rent

ly u

sed.

A s

ign

ifica

nt i

nver

se a

ssoc

iatio

n w

as f

ound

be

twee

n T

SP

an

d ad

mis

sion

fo

r ca

rdia

c di

seas

es;

hyd

roge

n su

lfide

dec

reas

ed a

nd

NO

x in

crea

sed

the

risk

of

card

iac

adm

issi

ons.

Afte

r m

utua

l ad

just

men

t fo

r th

e ot

her

cons

ider

ed

co-p

ollu

tant

s,

no

asso

ciat

ion

em

erge

d.

Per

cent

e

xces

s ris

k fo

r an

in

crem

ent o

f TS

P b

y 1

0 µ

g/m

3 . A

fter

adj

ustm

ent

for

met

eoro

logi

cal

fact

ors,

da

y an

d in

fluen

za:

-1.2

(-1

.9, -

0.5)

A

fter

furt

her

adju

stm

ent

for

all

the

co-p

ollu

tant

s co

nsid

ered

: 0.

2 (-

0.8,

1.2

).

report no. 4/11

125

TAB

LE II

I – S

HO

RT-

TER

M P

AR

TIC

ULA

TE M

ATT

ER E

XPO

SUR

E A

ND

RES

PIR

ATO

RY

HO

SPIT

AL

AD

MIS

SIO

NS

(Der

ived

from

EPA

TA

BLE

8B

-2).

Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

ode

ling

met

hods

: lag

s,

smoo

thin

g, c

o-po

lluta

nts

and

cova

riate

s.

Res

ults

and

Com

men

ts.

PM In

dex,

lag,

per

cent

exc

ess

risk%

(95%

LC

L, U

CL)

APH

EA 1

Sun

yer

et

al.

(199

7)

(Sun

yer

et a

l, 19

97)

Bar

celo

na (

86 -

92)

B

S M

edia

n: 4

0 B

S R

ange

: 11

-258

H

elsi

nki (

86 -

92)

B

S M

edia

n: -

B

S R

ange

: -

Par

is (

86 -

92)

B

S M

edia

n: 2

8 B

S R

ange

: 4-1

86

Lond

on (

86 -

92)

B

S M

edia

n: 1

3 B

S R

ange

: 3-9

5.

Thi

s st

udy

exa

min

ed t

he r

elat

ion

betw

een

BS

, S

O2,

NO

2, a

nd

O3,

and

dai

ly c

ount

s of

hos

pita

l ad

mis

sion

s fo

r as

thm

a an

d em

erge

ncy

visi

ts i

n ad

ults

(ag

es 1

5-64

yea

rs:

mea

n/da

y =

3.9

(B

);

0.7

(H);

13.

1 (L

); 7

.3 (

P))

and

chi

ldre

n (a

ges

<

15 y

ears

: m

ean/

day

= 0

.9 (

H);

19.

8 (L

); 4

.6 (

P))

. A

sthm

a (I

CD

9: 4

93)

was

stu

died

in

each

city

, bu

t th

e ou

tcom

e ex

amin

ed

diffe

red

acro

ss

citie

s:

ED

vi

sits

in

B

arce

lona

; em

erge

ncy

hosp

ital

asth

ma

adm

issi

ons

in

Lo

ndon

an

d H

elsi

nki,

and

tot

al a

sthm

a ad

mis

sion

s in

Par

is.

Est

imat

es

fro

m

all

citie

s ob

tain

ed

for

entir

e pe

riod

and

also

by

war

m o

r co

ld s

easo

ns,

usin

g tim

e-se

ries

GLM

re

gres

sion

, co

ntro

lling

fo

r te

mpe

ratu

re

and

RH

, vi

ral

epid

emic

s,

day

of

wee

k ef

fect

s, a

nd s

easo

nal

and

secu

lar

tren

ds

appl

ied

usin

g th

e A

PH

EA

stu

dy a

ppro

ach.

Dai

ly

adm

issi

ons

for

asth

ma

in

adul

ts

incr

ease

d si

gnifi

cant

ly

with

in

crea

sin

g am

bien

t le

vels

of

NO

2, a

nd

posi

tivel

y (b

ut

non-

sign

ifica

ntly

) w

ith B

S.

The

ass

ocia

tion

betw

een

asth

ma

adm

issi

ons

and

pollu

tion

varie

d ac

ross

citi

es,

likel

y du

e to

diff

erin

g as

thm

a ou

tco

mes

con

side

red.

In

child

ren,

da

ily a

dmis

sio

ns in

crea

sed

sign

ifica

ntly

with

S

O2

and

posi

tivel

y (b

ut

non-

sign

ifica

ntly

) w

ith B

S a

nd N

O2,

tho

ugh

the

latte

r on

ly i

n co

ld s

easo

ns.

No

asso

ciat

ion

wa

s ob

serv

ed

in c

hild

ren

for

O3.

Aut

hors

con

clud

ed t

hat

“I

n ad

ditio

n to

par

ticle

s, N

O2

and

SO

2 (b

y th

emse

lves

or

as a

con

stitu

ent

of a

pol

lutio

n m

ixtu

re)

may

be

im

port

ant

in

as

thm

a ex

acer

batio

ns”.

Exc

ess

risk

per

25

µg/

m3 B

S (

24

h A

vera

ge)

Ast

hma

Adm

issi

ons/

Vis

its:

<15

yea

rs.:

Lo

ndon

: 1.5

% (

lg 0

d)

Par

is: 1

.5%

(lg

2d)

T

otal

: 1.5

% (

-1.1

, 4.1

) 15

-64

year

s:

Bar

celo

na: 1

.8%

(lg

3d)

Lo

ndon

: 1.7

% (

lg 0

d)

Par

is: 0

.6%

(lg

0d)

T

otal

: 1.0

% (

-0.8

, 2.9

) T

wo

Pol

luta

nt (

per

25 µ

g/m

3 BS

) A

sthm

a A

dmis

sion

s (2

4 h

Avg

) <

15 y

ears

, (B

S &

NO

2):

Lond

on: 0

.6%

(lg

0d)

P

aris

: 2.9

% (

lg 2

d)

Tot

al: 1

.8%

(-0

.6, 4

.3)

<15

yea

rs, (

BS

& S

O2)

: Lo

ndon

: -1.

1% (

lg 0

d)

Par

is: -

1.4%

(lg

2d)

T

otal

: -1.

3 (-

5.0,

2.5

) 15

-64

year

s, (

BS

& N

O2)

: B

arce

lona

: 1.5

% (

lg 0

d)

Lond

on: -

4.7%

(lg

0d)

P

aris

: -0.

7% (

lg 1

d)

Tot

al: -

0.5%

(-5

.1, 4

.4).

report no. 4/11

126

APH

EA 2

Atk

inso

n

et

al.

(200

1)

(Atk

inso

n et

al,

2001

) E

ight

Eur

opea

n ci

ties

Med

ian/

rang

e B

arce

lona

1/9

4 -

12/9

6 P

M10

53.

3 (1

7.1,

131

.7)

Birm

ingh

am 3

/92

-12/

94

PM

10 2

1.5

(6.5

, 115

) Lo

ndon

1/9

2 -

12/9

4 P

M10

24.

9 (7

.2, 8

0.4)

M

ilan

-No

PM

10

(TS

P)

Net

herla

nds

1/9

2 -

9/95

P

M10

33.

4 (1

1.3,

130

.8)

Par

is 1

/92

- 9/

96

PM

13 2

0.1

(5.8

, 80.

9)

Rom

e -

No

PM

10 (

TS

P)

Sto

ckho

lm 3

/94

- 12

/96

PM

10 1

3.6

(4.3

, 43.

3).

As

part

of

th

e A

PH

EA

2

pr

ojec

t, as

soci

atio

n be

twee

n P

M1

0 an

d da

ily c

ount

s of

em

erg

ency

ho

spita

l adm

issi

ons

for

Ast

hm

a (0

-14

and

15-6

4 ye

ars)

, C

OP

D a

nd a

ll-re

spira

tory

dis

ease

(65

+

year

s)

regr

esse

d us

ing

GA

M,

cont

rolli

ng

for

envi

ronm

enta

l fac

tors

and

tem

pora

l pat

tern

s.

Thi

s st

udy

repo

rts

that

PM

wa

s as

soci

ated

w

ith d

aily

adm

issi

ons

for

resp

irato

ry d

isea

se

in a

sel

ectio

n o

f E

urop

ean

citi

es.

Ave

rage

da

ily

ozon

e

leve

ls

exp

lain

ed

a la

rge

prop

ortio

n of

the

bet

wee

n-ci

ty v

aria

bilit

y in

th

e si

ze o

f th

e pa

rtic

le e

ffect

est

imat

es i

n th

e ov

er 6

5 ye

ar a

ge g

roup

. In

chi

ldre

n, t

he

part

icle

eff

ects

wer

e co

nfo

unde

d w

ith N

O2

on a

day

-to-

day

basi

s.

For

10

µg/

m3 in

crea

se

Ast

hma

Ad

mis

sion

A

ge

0-

14

year

s:

PM

10 f

or c

ities

ran

ged

from

-0.

9%

(-2.

1, 0

.4)

to 2

.8%

(0.

8, 4

.8)

with

an

ove

rall

effe

ct e

stim

ate

of 1

.2%

(0

.2, 2

.3)

Ast

hma

Adm

issi

on

Age

15

-64

year

s:

Ove

rall

PM

1.1

% (

0.3,

1.8

) A

dmis

sion

of

CO

PD

and

Ast

hma

Age

65+

yea

rs:

Ove

rall

PM

1.0

% (

0.4,

1.5

) A

dmis

sion

A

ll R

espi

rato

ry

Dis

ease

Age

65+

yea

rs:

Ove

rall

PM

0.9

% (

0.6,

1.3

).

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Atk

inso

n et

al

. (1

999a

) (A

tkin

son

et a

l, 19

99a)

Lo

ndon

(92

- 9

4)

Pop

ulat

ion:

7.2

MM

P

M10

Mea

n: 2

8.5

10th-9

0th IQ

R: 1

5.8-

46.5

B

S m

ean:

12.

7 10

th-9

0th IQ

R: 5

.5-2

1.6

All-

age

resp

irat

ory

(mea

n=15

0.6/

day)

, al

l-age

as

thm

a (3

8.7/

day)

, C

OP

D p

lus

asth

ma

in a

dults

>

64

year

s (2

2.9/

day)

, an

d lo

wer

re

spira

tory

(6

4.1/

day)

in

ad

ults

>

64

year

s (1

6.7/

day)

ho

spita

l ad

mis

sion

s in

Lon

don

hosp

itals

wer

e co

nsid

ered

. C

ount

s fo

r ag

es

0-14

, 15

-64,

and

>

64 y

ears

we

re a

lso

exam

ined

. P

oiss

on G

LM

regr

essi

on w

as

used

, co

ntro

lling

for

sea

son,

day

of

w

eek,

m

eteo

rolo

gy,

auto

corr

elat

ion,

ov

erdi

sper

sio

n, a

nd in

fluen

za e

pide

mic

s.

Pos

itive

ass

oci

atio

ns w

ere

fou

nd b

etw

een

re

spira

tory

- re

late

d em

erge

ncy

hosp

ital

adm

issi

ons

and

PM

10

and

SO

2, b

ut n

ot f

or

O3

or

BS

. W

hen

SO

2

and

PM

10

wer

e in

clud

ed

sim

ulta

neou

sly,

si

ze

and

si

gnifi

canc

e o

f ea

ch w

as r

educ

ed.

Aut

hor

s co

nclu

ded

that

S

O2

and

PM

10

are

both

in

dica

tors

of

the

sam

e po

lluta

nt m

ix i

n th

is

city

. S

O2

and

PM

10 a

naly

ses

by t

empe

ratu

re

tert

ile

sugg

est

that

w

arm

se

ason

ef

fect

s do

min

ate.

O

vera

ll,

resu

lts

cons

iste

nt

with

ea

rlier

an

alys

es

for

Lond

on,

and

com

para

ble

with

th

ose

for

Nor

th

Am

eric

a an

d E

urop

e.

PM

10 (

50 µ

g/m

3 ), n

o co

-pol

luta

nt.

All

Re

spira

tory

Adm

issi

ons

: A

ll ag

e (la

g 1d

):

4.9%

(C

I: 1.

8,

8.1)

0-

14 (

lag

1d):

8.1

% (

CI:

3.5,

12.

9)

15-6

4 (la

g 2

d):

6.9%

(C

I:

2.1,

12

.9)

65+

(la

g 3d

): 4

.9%

(C

I: 0.

8, 9

.3)

Ast

hma

Adm

issi

ons:

A

ll ag

e (la

g 3d

): 3

.4%

(C

I: -1

.8,

8.9)

0-

14

(lag

3d):

5.

4%

(CI:

-1.2

, 12

.5)

15-6

4 (la

g 3

d):

9.4%

(C

I:

1.1,

18

.5)

65+

(la

g 0d

): 1

2% (

CI:

-1.8

, 27

.7)

CO

PD

&

A

sthm

a A

dmis

sion

s (6

5+; l

ag 3

): 8

.6%

(C

I: 2.

6, 1

5)

Low

er

Res

pira

tory

A

dmis

sion

s (6

5+;

lag

3d):

7.

6%

(CI:

0.

9,

14.8

).

report no. 4/11

127

And

erso

n et

al

. (1

998)

(A

nder

son

et a

l, 19

98)

Lond

on, 1

987-

1992

) P

opul

atio

n: 7

.2 M

M

BS

da

ily m

ean

: 14.

6 B

S 2

5-75

th IQ

R: 2

4-38

.

Poi

sson

GLM

log

-line

ar r

egre

ssio

n w

as

used

to

estim

ate

the

RR

of

Lo

ndon

da

ily

asth

ma

hosp

ital

adm

issi

ons

asso

ciat

ed w

ith c

hang

es i

n O

3, S

O2,

NO

2 an

d pa

rtic

les

(BS

) fo

r al

l age

s an

d fo

r 0-

14

year

s (m

ean=

19.5

/day

),

15-6

4 ye

ars

(mea

n=13

.1/d

ay)

and

65

+

year

s (m

ean

=2.

6/da

y).

Ana

lysi

s w

as

cont

rolle

d fo

r tim

e tr

ends

, se

ason

al

fact

ors,

ca

lend

ar

effe

cts,

in

fluen

za

epid

emic

s,

RH

, te

mpe

ratu

re,

and

auto

-cor

rela

tion.

Int

erac

tion

s w

ith c

o-po

lluta

nts

and

aero

alle

rgen

s w

ere

test

ed v

ia 2

po

lluta

nt

mod

els

and

mod

els

with

pol

len

coun

ts (

gras

s,

oak

and

birc

h).

Dai

ly h

ospi

tal

adm

issi

ons

for

asth

ma

we

re

foun

d to

hav

e as

soci

atio

ns

with

O3,

S

O2,

N

O2,

an

d B

S,

but

ther

e w

as

lack

of

co

nsis

tenc

y a

cros

s th

e ag

e gr

oups

in

the

spec

ific

pollu

tant

. B

S

ass

ocia

tion

was

st

rong

est

in t

he 6

5 +

gro

up,

espe

cial

ly i

n w

inte

r.

Pol

lens

w

ere

not

co

nsis

ten

tly

asso

ciat

ed

with

ho

spita

l ad

mis

sion

fo

r as

thm

a,

som

etim

es

bein

g po

sitiv

e,

som

etim

es

nega

tive.

A

ir po

llutio

n as

soci

atio

ns w

ith h

ospi

tal

adm

issi

ons

wer

e no

t ex

pla

ine

d by

ai

rbor

ne

polle

ns

in

sim

ulta

neou

s re

gres

sion

s, a

nd t

here

was

no

cons

iste

nt p

olle

n-po

lluta

nt in

tera

ctio

n.

Ast

hma

Ad

mis

sion

s.

BS

=25

µ

g/m

3 B

S L

ag 0

-3.

All

age:

5.9

8%

(0.

4, 1

1.9)

<

15: 2

.2%

(-4

.6, 9

.5)

15-6

4: 1

.2%

(-5

.3, 8

.1)

65+

: 22.

8%

(6.

1, 4

2.5)

B

S=

50

µg/

m3 ,

lag

2 &

co

-po

lluta

nt:

Old

er A

dult

(>64

yea

rs.)

Ast

hma

Vis

its:

BS

alo

ne: 1

4.6%

(2.

7, 2

7.8)

&

O3:

20.

0%

(3.

0, 3

9.8)

&

NO

2: 7

.4%

(-8

.7, 2

6.5)

S

O2:

11.

8%

(-2

.2, 2

7.8)

.

W

ong

et a

l. (2

002)

(W

ong

et a

l, 20

02)

Lond

on, U

K, 1

992-

1994

. m

ean

daily

co

ncen

trat

ion:

of

PM

10: 2

8.5.

The

pr

esen

t st

udy

exa

min

ed

the

rela

tion

betw

een

PM

10

and

othe

r co

-pol

luta

nts

(NO

2,

SO

2 an

d O

3),

and

daily

adm

issi

on f

or a

sthm

a (I

CD

9:

493)

fo

r ag

es

15-6

4 ye

ars,

an

d re

spira

tory

dis

ease

s (I

CD

9:

460-

519)

for

age

s 65

+

year

s in

th

e ci

ty

of

Lond

on.

The

sa

me

anal

yses

wer

e pe

rfor

med

for

the

city

of

Hon

g K

ong

(fin

ding

s no

t sh

ow

n in

the

pre

sent

rep

ort)

. P

oiss

on

regr

essi

on

was

us

ed

cont

rolli

ng

for

non-

para

met

ric

smoo

th

func

tions

of

tim

e,

tem

pera

ture

, hu

mid

ity,

influ

enza

epi

dem

ics,

day

of

the

wee

k, h

olid

ays

and

seas

ons.

An

a pr

iori

aver

age

lag

0-1

wa

s us

ed.

Est

imat

es f

or t

he

best

sin

gle

day

lag

(0,

1, 2

, 3)

wer

e al

so s

how

n.

The

ex

cess

ri

sks

of

hosp

italis

atio

n w

ere

al

so

sho

wn

afte

r m

utua

l ad

just

men

t fo

r ea

ch s

ingl

e co

-pol

luta

nt.

No

sign

ifica

nt

asso

ciat

ion

s ha

ve

bee

n sh

ow

n be

twee

n P

M10

and

hosp

ital

adm

issi

on

for

asth

ma

(15-

64

year

s)

and

resp

irato

ry d

isea

ses

(age

65+

), e

ven

afte

r al

low

ance

for

oth

er c

o-po

lluta

nts,

alth

ough

ex

cess

ris

ks w

ere

syst

ema

tical

ly o

ver

zero

. In

w

arm

se

aso

ns,

the

dire

ct

asso

ciat

ion

reac

hed

sta

tistic

al

sign

ifica

nce.

W

hen

co

nsid

erin

g th

e be

st

sing

le

lag

day,

a

sign

ifica

nt a

ssoc

iatio

n w

as f

ound

bet

we

en

PM

10 a

nd a

dmis

sion

for

bot

h as

thm

a an

d re

spira

tory

dis

ease

s.

NO

2 in

crea

sed

the

adm

issi

on

for

asth

ma

and

O3

the

one

of r

espi

rato

ry d

isea

ses.

Per

cent

exc

ess

ris

k (9

5% C

I) f

or

an

incr

emen

t of

P

M10

b

y 10

µ

g/m

3 ; R

espi

rato

ry

dis

ease

s,

age

65

+,

lag

0-1:

0.4

% (

-0.3

, 1.2

) W

arm

sea

son

s: 1

.8%

(0.

5, 3

.1)

Col

d se

ason

s: -

0.5%

(-1

.5, 0

.5)

Adj

uste

d fo

r N

O2:

0.9

% (

-0.3

, 2.0

) A

djus

ted

for

O3:

0.4

% (

-0.3

, 1.

2)

Adj

uste

d fo

r S

O2:

0.7

% (

-0.5

, 1.8

) La

g 3

(bes

t lag

): 1

.5%

(0.

8-2.

2)

Ast

hma,

age

15-

64, l

ag 0

-1:

1.4%

(-0

.1, 3

.0)

War

m s

easo

ns:

0.6

% (

-1.9

, 3.

1)

Col

d se

ason

s: 1

.6%

(-1

.5, 0

.5)

Lag

2 (b

est l

ag):

2.2

% (

0.8-

3.6)

.

report no. 4/11

128

Pon

ce

de

Leo

n et

al

. (1

996)

(P

once

de

Leon

et

al, 1

996)

Lo

ndon

, 4/1

987-

2/19

92.

Pop

ulat

ion:

7.3

mill

ion

B

S m

ean.

:14.

6 B

S 5

th-9

5th %

=6

– 27

.

Poi

sson

GLM

log

-line

ar r

egre

ssio

n an

alys

is o

f da

ily c

ount

s o

f ho

spita

l adm

issi

ons

(mea

ns/d

ay:

all

ages

=12

5.7

; A

ges

0-14

=45

.4;

Ag

es

15-

64=

33.6

; A

ges

65

+=

46.7

).

Effe

cts

of

tren

d,

seas

on a

nd

othe

r cy

clic

al

fact

ors,

day

of

the

wee

k,

holid

ays,

in

fluen

za

epid

emic

, te

mpe

ratu

re,

hum

idity

, an

d a

utoc

orre

latio

n w

ere

addr

esse

d. H

owe

ver,

tem

pera

ture

mod

eled

as

linea

r,

with

no

R

H

inte

ract

ion.

P

ollu

tion

va

riabl

es w

ere

BS

, S

O2,

O3,

and

NO

2, la

gge

d 0-

3 da

ys.

O3

asso

ciat

ed w

ith in

crea

se in

dai

ly h

ospi

tal

adm

issi

on,

espe

cial

ly in

the

"w

arm

" se

ason

. H

ow

ever

, U

-sha

pe o

f th

e O

3 do

se-r

espo

nse

sugg

ests

th

at

linea

r te

mp

erat

ure

cont

rol

wa

s no

t ad

equa

te.

Few

si

gnifi

cant

as

soci

atio

ns

wer

e fo

und

w

ith

othe

r po

lluta

nts,

but

the

se t

ende

d to

be

posi

tive

(esp

ecia

lly i

n co

ld s

easo

n, O

ct-M

arch

, an

d fo

r ol

der

indi

vidu

als

for

BS

).

Res

pira

tory

ho

spita

l ad

mis

sion

(a

ll ag

es);

BS

: 25

µg/

m3 :

Sin

gle

Pol

luta

nt M

odel

s

Oct

-Mar

; Lag

1: 0

.2%

(–1

.9,

2.3)

A

pr-S

ep; L

ag 1

: -2.

7% (

-6.0

, 0.8

) R

espi

rato

ry

hos

pita

l ad

mis

sion

s (>

65)

Sin

gle

Pol

luta

nt M

odel

s; B

S:

25

µg/

m3

Oct

-Mar

; Lag

2: 1

.2%

(-2

.1, 4

.5)

Apr

-Sep

; La

g 2:

: 4.

5%

(-1.

0,

10.4

).

Wor

dley

et a

l. (1

997)

(W

ordl

ey e

t al,

1997

) B

irmin

gham

, U

K,

4/19

92

–3/1

994.

P

M10

dai

ly v

alue

s:

Mea

n: 2

5.6

rang

e: 2

.8, 1

30.9

P

M10

3 d

ay m

ean:

M

ean:

25.

5 ra

nge:

7.3

, 104

.7.

Rel

atio

n be

twee

n P

M1

0

and

tota

l ho

spita

l ad

mis

sion

fo

r re

spira

tory

(m

ean

=

21.8

/day

),

asth

ma

(mea

n=6.

2/da

y),

bron

chiti

s (m

ean=

2.4/

day)

, pn

eum

onia

(m

ean=

3.4/

day)

, an

d C

OP

D

(mea

n=3.

2/da

y)

was

an

alyz

ed,

usin

g lo

g-lin

ear

reg

ress

ion

afte

r ad

just

men

t fo

r da

y of

w

eek,

m

onth

, lin

ear

tr

end,

R

H,

and

tem

pera

ture

(b

ut

not

tem

pera

ture

-RH

in

tera

ctio

n).

PM

10 p

ositi

vely

ass

ocia

ted

with

all

hosp

ital

adm

issi

ons

for

resp

irato

ry,

asth

ma,

br

onch

itis,

pn

eum

onia

, an

d C

OP

D.

Pne

umon

ia,

all

resp

irato

ry,

and

asth

ma

hosp

ital

adm

issi

ons

also

si

gnifi

cant

ly

posi

tivel

y as

soci

ated

with

the

mea

n of

PM

10

over

the

pas

t th

ree

days

, w

hich

gav

e 1

0 to

20

%

grea

ter

RR

’s

per

10 μg

/m3 ,

as

expe

cted

gi

ven

smal

ler

day

to

day

devi

atio

ns.

Oth

er

air

pollu

tant

s w

ere

exam

ine

d bu

t no

t pr

esen

ted,

as

“the

se d

id

not

have

a

si

gnifi

cant

as

soci

atio

n

with

he

alth

out

com

es i

ndep

ende

nt f

rom

tha

t of

P

M10

”.

50 µ

g/m

3 in P

M10

A

ll R

espi

rato

ry

hosp

ital

adm

issi

ons

(all

ages

) La

g 0:

12.

6% (

5.7,

20)

A

sthm

a ho

spita

l ad

mis

sion

s (a

ll ag

es)

Lag

2: 1

7.6%

(3,

34.

4)

Bro

nchi

tis h

ospi

tal a

dmis

sio

ns (

all

ages

) La

g 0:

32.

6% (

4.4,

68.

3)

Pne

umon

ia

hos

pita

l ad

mis

sion

s (a

ll ag

es)

Lag

3: 3

1.9%

(15

, 51.

4)

CO

PD

ho

spita

l ad

mis

sion

s (a

ll ag

es)

Lag

1: 1

1.5%

(-3

, 28.

2).

McG

rego

r et

al

. (1

999)

(M

cGre

gor

et a

l, 19

99)

Birm

ingh

am,

UK

. M

ean

PM

10: 3

0.0.

A

syno

ptic

cl

imat

olog

ical

ap

proa

ch

used

to

in

vest

igat

e lin

kage

s be

twe

en

air

mas

s ty

pes

(wea

ther

si

tuat

ions

),

PM

10,

and

all

resp

irato

ry

hosp

ital

adm

issi

ons

(mea

n=

19.2

/day

) fo

r th

e B

irmin

gham

are

a.

Thi

s st

udy

resu

lts s

how

dis

tinct

diff

eren

tial

resp

onse

s of

res

pira

tory

adm

issi

on r

ates

to

the

six

win

ter

air

mas

s ty

pes.

Tw

o of

thr

ee

type

s of

air

mas

ses

asso

cia

ted

with

abo

ve-

aver

age

adm

issi

on

rate

s al

so

favo

r hi

gh

PM

10 l

evel

s. T

his

is s

ugg

est

ive

of p

ossi

ble

linka

ge

betw

een

w

eath

er,

air

qual

ity,

and

he

alth

.

Est

imat

es n

ot r

epor

ted

report no. 4/11

129

And

erso

n et

al

. (2

001)

(A

nder

son

et a

l, 20

01)

Wes

t Mid

land

, E

ngla

nd

(Oct

ober

199

4-D

ecem

ber

1996

) P

opul

atio

n: 2

.3 m

illio

n

PM

10 m

ean:

23.

3 P

M2.

5 m

ean:

14.

5 P

M10

-2.5: 9

.0.

Res

pira

tory

hos

pita

l ad

mis

sion

s (m

ean:

66/

day)

re

late

d to

P

M10

, P

M2.

5,

PM

10-2

.5,

BS

, su

lfate

, N

O2,

O3,

SO

2, C

O.

GLM

re

gres

sion

with

qua

si-

likel

ihoo

d ap

proa

ch,

cont

rolli

ng

for

seas

onal

pa

ttern

s,

tem

p,

hum

idity

, in

fluen

za

epis

odes

, da

y of

w

eek.

A

djus

ted

fo

r re

sidu

al

seria

l co

rrel

atio

n an

d ov

er-d

ispe

rsio

n.

Res

pira

tory

adm

issi

ons

(all

ages

) w

ere

not

asso

ciat

ed w

ith a

ny p

ollu

tant

. A

naly

ses

by

age

reve

aled

so

me

asso

ciat

ions

to

P

M10

an

d P

M2.

5 a

nd r

espi

rato

ry a

dmis

sion

s in

the

0-

14

age

grou

p.

The

re

wa

s a

strik

ing

seas

onal

in

tera

ctio

n in

th

e co

ol

seas

on

vers

us

the

war

m

seas

on.

PM

10-2

.5

effe

cts

cann

ot b

e ex

clud

ed.

Tw

o po

lluta

nt m

odel

s ex

amin

ed

par

ticul

ate

mea

sure

s.

PM

2.5

effe

cts

redu

ced

by in

clus

ion

of b

lack

sm

oke.

Res

pira

tory

ho

spita

l ad

mis

sion

(la

g 0-

1);

PM

10 i

ncre

men

t 10

-90%

(1

1.4-

38.3

µg/

m3 ):

A

ll ag

es: 1

.5 (

-0.7

, 3.6

) A

ges

0-14

: 3.9

(0.

6, 7

.4)

Age

s 15

-64:

0.1

(-4

.0, 4

.4)

Age

s 65

: -1.

1 (-

4.3,

2.1

) P

M2.

5 (6

.0-2

5.8)

A

ll ag

es: 1

.2 (

-0.9

, 3.4

) A

ges

0-14

: 3.4

(-0

.1, 7

.0)

Age

s 15

-64:

-2.

1 (-

6.4,

2.4

) A

ges

65: -

1.3

(-4.

7, 2

.2)

PM

10-2

.5 (

4.1,

15.

2)

All

ages

: 0.2

(-2

.5, 3

.0)

Age

s 0-

14: 4

.4 (

-0.3

, 9.4

) A

ges

15-6

4: -

4.9

(-9.

9, 0

.4)

Age

s 65

: -1.

9 (-

6.0,

2.5

) C

OP

D (

ICD

9: 4

90-4

92, 4

94-4

96)

PM

10:

Age

65

+: -

1.8

(-6.

9, 3

.5)

PM

2.5:

Age

65

+: -

3.9

(-9.

0, 1

.6)

PM

10-2

.5: A

ge 6

5+: -

1.7

(-8.

9, 5

.3)

Ast

hma

(IC

D9

: 493

) (la

g 0-

1)

PM

10;

Age

s 0-

14: 8

.3 (

1.7,

15.

3)

PM

10;

Age

s 15

-64:

-2

.3

(-10

.0,

6.1)

P

M2.

5; A

ges

0-14

: 6.0

(-0

.9, 1

3.4)

P

M2.

5;A

ges

15-

64:

-8.4

(-

16.4

, 0.

3)

PM

10-2

.5;

Age

s 0-

14:

7.1

(-

2.1,

17

.2)

PM

10-2

.5;

Age

s 15

-64:

-10

.7 (

-19.

9,

-0.5

)

T

hom

pson

et

al

. (2

001)

(T

hom

pson

et a

l, 20

01)

Bel

fast

, N

orth

ern

Irel

and

1/1/

93 –

12

/31/

95.

PM

10 m

ean

(SD

) M

ay

– O

ctob

er

24.9

(1

3.7)

N

ovem

ber

– A

pril

31.9

(2

4.3)

The

ra

tes

of

acut

e as

thm

a ad

mis

sion

to

ch

ildre

n’s

emer

genc

y w

as s

tudi

ed i

n re

latio

n to

da

y-to

-day

flu

ctua

tion

of

PM

10

and

othe

r po

lluta

nts

usin

g G

LM P

oiss

on

regr

essi

on.

A w

eak

, bu

t si

gnifi

cant

ass

oci

atio

n be

twee

n P

M10

con

cent

ratio

n an

d as

thm

a em

erge

ncy-

de

part

men

t ad

mis

sion

s w

as

seen

. A

fter

adju

stin

g fo

r m

ultip

le

pollu

tant

s on

ly

the

benz

ene

leve

l w

as

inde

pend

ently

as

soci

ated

w

ith

asth

ma

emer

genc

y de

part

men

t ad

mis

sion

. B

enze

ne w

as h

ighl

y co

rrel

ated

to P

M10

, S

O2

and

NO

2 le

vels

.

—

report no. 4/11

130

Pre

scot

t et

al

. (1

998)

(P

resc

ott e

t al,

1998

) E

dinb

urgh

(1

0/19

92-

6/19

95).

P

opul

atio

n: 0

.45

MM

P

M10

mea

n.:2

0.7

PM

10 m

in/m

ax=

5/72

P

M10

90th

-10t

h%

: 20.

Poi

sson

lo

g-lin

ear

regr

essi

on

mod

els

use

d to

in

vest

igat

e re

latio

n of

dai

ly h

ospi

tal

adm

issi

ons

with

NO

2, O

3, C

O,

and

PM

10.

Adj

ustm

ents

wer

e

mad

e fo

r se

ason

al

and

day

of

wee

k,

daily

te

mpe

ratu

re

(usi

ng

8 du

mm

y va

riabl

es),

an

d w

ind

spee

d.

Sep

arat

e a

naly

ses

for

age<

65

year

s (m

ean

resp

irato

ry

hosp

ital

adm

issi

on:

3.4/

day)

and

age

>64

yea

rs (

mea

n re

spira

tory

ho

spita

l ad

mis

sion

: 8.

7/da

y),

and

for

subj

ects

w

ith m

ultip

le h

ospi

tal a

dmis

sion

s.

PM

10 w

as c

onsi

sten

tly p

osi

tivel

y as

soci

ate

d w

ith R

esp

irato

ry h

ospi

tal a

dm

issi

ons

in b

oth

ag

e gr

oups

, w

ith t

he g

reat

est

effe

ct s

ize

in

thos

e >

64,

espe

cial

ly

amo

ng t

hose

with

>4

hosp

ital

adm

issi

ons

duri

ng

1981

-199

5.

Wea

k si

gnifi

canc

es l

ikel

y co

ntrib

uted

to

by

low

pop

ulat

ion

siz

e.

Sin

gle

Pol

luta

nt M

odel

s P

M10

: 50

µg/

m3 , l

ag 1

-3

Res

pira

tory

h

ospi

tal

adm

issi

ons

(age

<65

): 1

.25%

(-1

2.8,

17.

5)

Res

pira

tory

h

ospi

tal

adm

issi

ons

(age

>64

): 5

.33%

(-9

.3, 2

2.3

) R

espi

rato

ry

hos

pita

l ad

mis

sion

s (a

ge>

64,

>4

hos

pita

l adm

issi

ons)

: 7.

93%

(-1

9.0,

43.

7).

SWED

EN

Hag

en

et

al.

(200

0)

(Hag

en e

t al,

2000

) D

ram

men

, S

wed

en

(11/

1994

-12/

1997

) P

opul

atio

n: 1

10,

000

PM

10 m

ean:

16.

8 P

M10

IQR

: 9.

8-2

0.9.

Exa

min

ed

PM

10,

SO

2,

NO

2,

VO

C’s

, an

d O

3 as

soci

atio

ns

with

re

spira

tory

ho

spita

l ad

mis

sion

s fr

om o

ne h

ospi

tal

(mea

n =

2.2

/day

).

Use

d P

oiss

on

GA

M c

ontr

ollin

g fo

r te

mpe

ratu

re

and

RH

(b

ut

not

thei

r in

tera

ctio

n),

lon

g-w

ave

and

seas

onal

ity,

day

of

wee

k,

holid

ays,

an

d in

fluen

za e

pid

emic

s.

As

a si

ngle

pol

luta

nt,

the

PM

10 e

ffect

was

of

sam

e or

der

of

mag

nitu

de

as

repo

rted

in

ot

her

stud

ies.

T

he

PM

10

asso

ciat

ion

decr

ease

d w

hen

othe

r po

lluta

nts

wer

e ad

ded

to t

he m

odel

. H

ow

ever

, th

e V

OC

’s

sho

wed

the

stro

nges

t ass

ocia

tions

.

Res

pira

tory

h

ospi

tal

adm

issi

ons

(all

ages

) fo

r IQ

R=

50 µ

g/m

3

-Sin

gle

Pol

luta

nt M

odel

: P

M10

(la

g 0)

: 18.

3% (

-4.2

, 46

) -T

wo

Pol

luta

nt M

odel

(w

ith O

3):

PM

10 (

lag

0): 1

8.3%

(-4

.2, 4

5.4

) -T

wo

Pol

luta

nt

Mod

el

(with

B

enze

ne):

P

M10

(la

g 0)

: 6.5

% (

-14

, 31.

8).

NO

RW

AY

O

fteda

l et

al

. (2

003)

(O

fteda

l et a

l) D

ram

men

, N

orw

ay,

1995

-20

00.

Pop

ulat

ion:

11

0,00

0 P

M10

mea

n (S

D):

to

tal p

erio

d: 1

6.6

(10.

2).

1995

-199

7: 1

6.8

(10.

2).

1998

-200

0: 1

6.5

(10.

3).

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

PM

10,

and

othe

r co

-pol

luta

nts

(incl

udin

g

SO

2,

NO

2 an

d

O3)

an

d re

spira

tory

h

ospi

tal

adm

issi

ons

in D

ram

men

(m

ean

= 2

.3/d

ay).

T

ime-

serie

s an

alys

is o

f co

unts

was

per

form

ed

by m

eans

of

GA

M w

ith l

og l

ink

and

Poi

sson

di

strib

utio

n,

cont

rolli

ng

for

time

tren

ds.

Lag

0 w

as

appa

rent

ly u

sed.

PM

10 d

id n

ot s

igni

fican

tly i

ncr

ease

hos

pita

l ad

mis

sion

for

res

pira

tory

dis

ease

s. A

dire

ct

asso

ciat

ion

was

fou

nd f

or N

O2

and

SO

2. N

o as

soci

atio

n w

ith O

3. D

ivid

ing

the

tota

l st

udy

perio

d in

to t

wo

3-ye

ar p

erio

ds,

anal

yses

for

th

e se

cond

tim

e pe

riod

show

ed

wea

ker

asso

ciat

ion

bet

we

en

thes

e

pollu

tant

s an

d th

e he

alth

out

com

e.

Per

cent

exc

ess

ris

k of

res

pira

tory

ho

spita

l ad

mis

sion

s fo

r 11

.04

µg/

m3 (

IQR

):

Sin

gle

Po

lluta

nt M

odel

; P

M10

(la

g 0)

T

otal

per

iod:

2.1

% (

-1.0

, 5.3

) 19

94-1

997:

3.5

% (

-1.0

, 8.3

) 19

98-2

000:

-0.

8% (

-5.2

, 3.7

) T

wo

Pol

luta

nt

Mod

el

(with

be

nzen

e): 1

.0%

(-2

.2, 4

.3)

Tw

o P

ollu

tant

Mod

el (

with

NO

2):

-0.3

% (

-4.1

, 3.7

).

report no. 4/11

131

THE

NET

HER

LAN

DS

S

chou

ten

et

al.

(199

6)

(Sch

oute

n et

al,

1996

) A

mst

erda

m/R

otte

rdam

, 19

77-1

989.

A

mst

erda

m

Pop

.: 0.

69

MM

R

otte

rdam

Po

p.: 0

.58

MM

A

mst

erda

m:

BS

mea

n.:1

1

BS

5th

-95t

h%

: 1

- 37

R

otte

rdam

: B

S m

ean.

:26

B

S 5

th-9

5th %

= 6

-61.

Dai

ly

emer

gen

cy

hosp

ital

adm

issi

on

for

resp

irato

ry

dise

ases

(I

CD

9:

460-

519)

, C

OP

D

(490

-492

, 49

4,

496)

, an

d as

thm

a (4

93).

T

he

mea

n H

A/d

(ra

nge)

for

the

se w

ere:

6.7

0 (0

-23)

, 1.

74

(0-9

) an

d 1.

13

(0-7

) re

spec

tivel

y in

A

mst

erda

m

and

4.79

(0

-19)

, 1.

57

(0-9

),

and

0.53

(0

-5)

in

Rot

terd

am.

Hos

pita

l ad

mis

sion

as

soci

atio

ns w

ith B

S,

O3,

NO

2, a

nd S

O2

wer

e an

alyz

ed,

usin

g au

tore

gres

sive

P

oiss

on

GLM

re

gres

sion

al

low

ing

for

ove

rdis

pers

ion

an

d co

ntro

lling

fo

r se

ason

, da

y of

w

eek,

m

eteo

rolo

gica

l fac

tors

, and

influ

enza

epi

dem

ics.

BS

did

not

sho

w a

ny c

onsi

sten

t ef

fect

s in

A

mst

erda

m;

but

in

Rot

terd

am

BS

w

as

posi

tivel

y re

late

d to

ad

mis

sion

s.

Mos

t co

nsis

tent

BS

as

soci

atio

ns

in a

dults

>64

ye

ars.

in

win

ter.

Pos

itive

O3

asso

ciat

ion

in

sum

mer

in

peop

le a

ged

>6

4 in

Am

ster

dam

an

d R

otte

rda

m.

SO

2 a

nd

NO

2 di

d no

t sh

ow

any

clea

r ef

fect

s. R

esul

ts d

id n

ot c

hang

e in

po

lluta

nt i

nter

actio

n an

alys

es.

The

aut

hors

co

nclu

ded

that

sh

ort-

term

ai

r po

llutio

n-

emer

genc

y ad

mis

sion

as

soci

atio

n is

n

ot

alw

ays

cons

iste

nt a

t th

ese

indi

vidu

al c

itie

s’

rela

tivel

y lo

w

coun

ts

of

daily

ho

spita

l ad

mis

sion

s a

nd l

ow l

eve

ls o

f ai

r po

llutio

n.

Ana

lyse

s fo

r al

l ag

es o

f al

l th

e N

ethe

rland

s ga

ve

a st

rong

B

S-h

ospi

tal

adm

issi

on

asso

ciat

ion

in w

inte

r.

Sin

gle

Pol

luta

nt M

odel

s F

or B

S=

25 µ

g/m

3 , lag

2;

For

all

of th

e N

ethe

rland

s:

Res

pira

tory

h

ospi

tal

adm

issi

ons

(all

ages

):

Win

ter:

2.0

% (

-1.5

, 5.7

) S

umm

er: 2

.4%

(0.

6, 4

.3).

GER

MA

NY

W

ichm

ann

(2

004)

(W

ichm

ann,

200

4)

Rhi

ne-R

uhr

area

, G

erm

any,

1

985,

si

ngle

ep

isod

e. T

SP

dur

ing

the

epis

ode

in

Rhi

ne-R

uhr

area

: ~ 6

00.

In

Janu

ary

1985

an

ex

ten

ded

smog

ep

isod

e oc

curr

ed i

n C

entr

al E

urop

e. T

his

pape

r re

vie

ws

the

heal

th

effe

cts,

in

clud

ing

resp

irato

ry

adm

issi

on,

inve

stig

ated

dur

ing

the

smog

per

iod

and

a co

ntro

l pe

riod

befo

re a

nd a

fter

the

smog

ep

isod

e.

The

Rhi

ne-R

uhr

are

a (W

este

rn G

erm

any)

was

af

fect

ed f

or 5

day

s w

ith m

axi

mum

con

cent

ratio

n of

T

SP

of

60

0 µ

g/m

3 (2

4h

aver

age

s).

In

Aug

sbur

g (S

outh

ern

Ger

man

y)

the

smog

ep

isod

e w

as l

ess

seve

re (

100

µg/

m3 T

SP

, 24

h

aver

ages

).

Rhi

ne-R

uhr

hos

pita

l ad

mis

sion

s in

crea

sed

by 3

9% f

or c

hron

ic b

ronc

hitis

, by

7%

(no

t si

gnifi

cant

) fo

r re

spira

tory

di

seas

es,

and

de

crea

sed

by

14%

fo

r as

thm

a (n

ot

sign

ifica

nt).

No

risk

sho

wn

.

report no. 4/11

132

FRA

NC

E

Dab

et

al.

(199

6) (

Dab

et

al, 1

996)

P

aris

, F

ran

ce

(198

7-19

92)

Pop

ulat

ion:

6.1

MM

P

M13

mea

n: 5

0.8

PM

13 5

th-9

5th r

ange

: 19

.0-

137.

3 B

S m

ean:

31.

9 B

S

5th-9

5th

Ran

ge:1

1.0-

123.

3.

Dai

ly m

orta

lity

and

gene

ral

adm

issi

ons

to P

aris

pu

blic

ho

spita

ls

for

resp

irato

ry

caus

es

wer

e

cons

ider

ed

(mea

ns:

all

resp

irato

ry=

79/d

ay,

asth

ma=

14/d

ay,

C

OP

D=

12/d

ay).

T

ime

serie

s an

alys

is u

sed

lin

ear

regr

essi

on m

odel

fo

llow

ed

by a

Po

isso

n re

gres

sion

adj

uste

d fo

r ep

idem

ics

of in

fluen

za A

and

B,

tem

pera

ture

, RH

, ho

liday

s,

day

of w

eek,

tre

nd,

long

-wa

ve v

aria

bilit

y, a

nd

nurs

es’

strik

e.

No

two

po

lluta

nt

mod

els

cons

ider

ed.

For

the

all

resp

irato

ry c

ause

s ca

tego

ry,

the

auth

ors

foun

d “t

he

stro

nge

st

asso

ciat

ion

wa

s ob

serv

ed w

ith P

M13

” fo

r bo

th h

ospi

tal

adm

issi

ons

and

mor

talit

y,

indi

catin

g

a co

here

nce

of a

ssoc

iatio

n ac

ross

out

com

es.

Ast

hma

was

si

gnifi

cant

ly

corr

elat

ed

with

N

O2

leve

ls, b

ut n

ot P

M13

.

Fo

r P

M13

: 5

0 µ

g/m

3 ;

BS

: 25

µ

g/m

3 ; R

espi

rato

ry a

dmis

sion

s (a

ll ag

es)

PM

13 L

ag 0

: 2.2

% (

0.2,

4.3

) B

S L

ag 0

: 1.0

% (

0.2,

1.8

) C

OP

D a

dmis

sion

s (a

ll ag

es)

PM

13 L

ag 2

: 2.3

% (

-6.7

, 2.2

) B

S L

ag 2

: 1.1

% (

-2.9

, 0.6

) A

sthm

a ad

mis

sion

s (a

ll ag

es):

P

M13

Lag

2: 1

.3%

(-4

.6, 2

.2)

BS

Lag

0: 1

.2%

(-0

.5, 2

.9)

Eils

tein

et

al

(2

004)

(E

ilste

in e

t al,

2004

) N

ine

Fre

nch

citie

s, 1

990-

1997

. N

o da

ta

dist

ribut

ion

was

re

port

ed.

Thi

s st

udy

exa

min

ed t

he s

hort

-ter

m e

ffect

s of

P

M10

, B

S

an

d ot

her

co-p

ollu

tant

s (C

O,

NO

2,

SO

2,

O3)

on

m

orta

lity

and

hosp

italis

atio

n fo

r ca

rdio

vasc

ular

or

resp

irato

ry d

isor

ders

in

nine

F

renc

h ci

ties

(Bor

deau

x, L

e H

avre

, Li

lle,

Lyon

, M

arse

ille,

P

aris

, R

ouen

, S

tras

bour

g

and

Tou

lous

e)

of

the

Sur

veill

ance

A

ir et

S

ante

pr

ogra

m.

The

an

alys

is

asse

ssed

th

e ci

ty-

spec

ific

and

com

bine

d as

soci

atio

ns w

ith v

ario

us

pollu

tant

s us

ing

Poi

sson

GA

M,

afte

r ad

just

men

t fo

r tr

ends

in

seas

ons,

day

of

wee

k, h

olid

ays,

in

fluen

za e

pid

emic

s, t

empe

ratu

re a

nd h

um

idity

. A

com

bine

d R

R w

as c

alcu

late

d fo

r al

l the

citi

es.

Lag

0-1

and

Lag

0-5

wer

e u

sed.

At

sele

cted

la

gs,

som

e di

rect

ass

ocia

tion

s w

ere

fou

nd b

etw

een

both

PM

10 a

nd B

S,

and

ad

mis

sion

fo

r re

spira

tory

di

seas

es,

part

icul

arly

in

ch

ildre

n ag

ed

0-14

ye

ars.

S

tron

ger

asso

ciat

ions

wer

e f

ound

for

SO

2,

NO

2 an

d pa

rtic

ular

ly fo

r C

O.

Effe

cts

com

put

ed

for

10

µg/

m3

chan

ge in

exp

ositi

on:

Lag

0-1

PM

10; a

ge 1

5-64

: 0.0

NS

P

M10

; age

65

+: 0

.8 N

S

Lag

0-5

PM

10; a

ge 1

5-64

: 1.7

p<

0.05

P

M10

; age

65

+: 1

.4 p

<0.

05

Lag

0-1

BS

; age

15-

64: 1

.8 p

<0.

05

BS

; age

65+

: 0.

0 N

S

Lag

0-5

BS

; age

15-

64: 4

.7 p

<0.

05

BS

; age

65+

: 0.

0 N

S.

report no. 4/11

133

ITA

LY

Big

geri

et

al.

(200

5)

(Big

geri

et a

l, 20

05)

Eig

ht

citie

s of

N

orth

, C

entr

e an

d S

outh

of

Italy

, 19

90-1

999.

P

M10

m

ean

da

ily

conc

entr

atio

n:

Tur

in, 9

1-94

: 77.

6 T

urin

, 95-

98: 6

3.8

Mila

n, 9

0-94

: 61.

8 M

ilan,

95-

97: 4

5.2

Ver

ona,

95-

99: 3

6.5

Rav

enna

, 91-

95: 5

9.1

Bol

ogna

, 96-

98:

41.

2 F

lore

nce,

96-

98: 4

0.3

Rom

e, 9

2-94

: 69.

7 P

aler

mo,

97-

99: 4

2.9.

Met

a-an

alys

is

of

shor

t-te

rm

effe

cts

of

air

pollu

tion

on m

orta

lity

(all

caus

es,

card

iova

scul

ar

caus

es

and

resp

irato

ry

caus

es)

and

hosp

ital

adm

issi

on

(car

diac

ca

use

s,

and

resp

irato

ry

caus

es –

IC

D9:

460

-519

) in

eig

ht I

talia

n c

ities

fr

om

1990

to

19

99.

Dai

ly

conc

entr

atio

ns

of

pollu

tant

s w

ere

colle

cted

. A

gen

eral

ized

lin

ear

mod

el

adju

sted

fo

r ag

e,

day

of

the

w

eek,

ho

liday

s,

influ

enza

ep

ide

mic

s,

met

eoro

logi

cal

varia

bles

, an

d s

easo

nalit

y p

atte

rn w

as

fitte

d fo

r P

M10

and

oth

er

co-p

ollu

tant

(S

O2,

NO

2, C

O,

and

O3)

. Lag

0-3

was

use

d fo

r ho

spita

l adm

issi

on.

A s

igni

fican

t di

rect

ass

ocia

tion

was

fou

nd

betw

een

PM

10

and

resp

irato

ry

hosp

ital

adm

issi

on.

NO

2 an

d C

O s

how

ed s

tron

ger

as

soci

atio

ns.

Effe

cts

com

put

ed

for

10

µg/

m3

chan

ge in

PM

10 (

lag

0-3

avg

.):

Fix

ed-e

ffect

s: 0

.73%

(0.

27,

1.20

) R

ando

m-e

ffect

s:

0.91

%

(-0.

04,

1.86

).

Vig

otti

et

al.

(199

6)

(Vig

otti

et a

l, 1

996)

M

ilan,

Ialy

, 19

80-1

989

Pop

ulat

ion:

1.5

MM

T

SP

mea

n: 1

39.

0 T

SP

IQR

: 82.

0, 1

75.7

.

Ass

ocia

tion

betw

een

ad

ult

resp

irato

ry

(15-

64

year

s m

ean

=11

.3/d

ay,

and

65 +

yea

rs m

ean

=8.

8/da

y) a

nd a

ir po

llutio

n e

valu

ated

, us

ing

the

AP

HE

A p

roto

col.

Poi

sson

reg

ress

ion

wa

s us

ed

afte

r ad

just

men

t fo

r w

eath

er

and

long

te

rm

tren

d, y

ear,

influ

enza

epi

dem

ics,

and

sea

son.

Incr

ease

d ris

k of

re

spira

tory

ho

spita

l ad

mis

sion

w

as

asso

ciat

ed

with

bo

th

SO

2 an

d T

SP

. T

he r

elat

ive

risks

wer

e si

mila

r fo

r bo

th p

ollu

tant

s. T

here

wa

s no

mod

ifica

tion

of t

he T

SP

eff

ect

by S

O2

leve

l. T

here

was

a

sugg

estio

n o

f a

high

er

TS

P

effe

ct

on

hosp

ital a

dmis

sion

s in

the

cool

mon

ths.

You

ng

Adu

lt (1

5-64

ye

ars.

) R

espi

rato

ry

adm

issi

on

per

100

µg/

m3 in

crea

se in

TS

P:

Lag

2: 5

% (

CI:

0, 1

0)

Old

er

Adu

lt (6

5+

year

s.)

Res

pira

tory

ad

mis

sion

pe

r 10

0 µ

g/m

3 incr

ease

in T

SP

: La

g 1

ER

: 5%

(C

I: -1

, 10)

.

F

usco

et

al

. (2

001)

(F

usco

et a

l, 20

01)

Rom

e, It

aly,

199

5-19

97.

PM

– s

uspe

nded

par

ticle

s m

easu

red.

Dai

ly

cou

nts

of

hosp

ital

adm

issi

ons

for

tota

l re

spira

tory

co

nditi

ons,

ac

ute

resp

irato

ry

infe

ctio

n in

clud

ing

pneu

mon

ia,

CO

PD

, an

d as

thm

a w

as

anal

yzed

in

re

latio

n to

P

M

mea

sure

s a

nd

gase

ous

pollu

tant

s us

ing

gene

raliz

ed a

dditi

ve G

AM

mod

els

cont

rolli

ng f

or

mea

n te

mpe

ratu

re,

influ

enza

, ep

ider

mic

s, a

nd

othe

r fa

ctor

s us

ing

splin

e sm

ooth

s.

No

effe

ct

wa

s fo

und

for

PM

. T

otal

re

spira

tory

ad

mis

sion

w

ere

si

gnifi

cant

ly

asso

ciat

ed w

ith s

ame-

day

leve

l of

NO

2 a

nd

CO

. T

here

wa

s no

indi

catio

n t

hat

the

effe

cts

of a

ir po

llutio

n w

ere

pres

ent

at la

gs >

2 d

ays.

A

mon

g ch

ildre

n,

tota

l re

spira

tory

an

d as

thm

a ad

mis

sion

s w

ere

stro

ngly

as

soci

ated

with

NO

2 an

d C

O.

Mul

tipol

luta

nt

mod

el

anal

ysis

yi

elde

d w

eak

er

and

mo

re

unst

able

res

ults

.

—

report no. 4/11

134

San

seba

stia

no

et

al.

(200

3)

(San

seba

stia

no

et

al,

2003

) P

arm

a, It

aly,

199

2-20

01.

Mea

n da

ily c

onc

entr

atio

n:

PM

10

(199

8-2

001)

: fr

om

39,6

3 in

199

8 t

o 57

.68

in

2001

; T

SP

: fr

om 4

6.92

in

1996

to 6

2.39

in 1

992.

Thi

s st

udy

exam

ined

the

rel

atio

nshi

p be

twee

n T

SP

an

d ot

her

co

-pol

luta

nts

(CO

, N

O2,

an

d S

O2)

, an

d da

ily h

ospi

tal

adm

issi

on f

or s

peci

fic

resp

irato

ry

dise

ases

(in

clud

ing

B

PC

O,

polm

oniti

s,

ple

uriti

s,

asth

ma

and

resp

irato

ry

sym

ptom

s)

in

the

city

of

P

arm

a (p

opul

atio

n 17

0,00

0).

The

exc

ess

risk

of

hosp

ital

adm

issi

on

wa

s no

t an

alys

ed f

or P

M10

sin

ce i

nfor

mat

ion

for

PM

10 w

as a

vaila

ble

for

the

perio

d 19

98-

2001

, on

ly.

A

dire

ct

ass

ocia

tion

has

been

sh

ow

n

betw

een

TS

P,

NO

2 an

d S

O2,

and

adm

issi

on

for

sele

cted

res

pira

tory

dis

eas

es.

Effe

cts

com

put

ed

for

1 µ

g/m

3 in

crem

ent o

f TS

P:

0.14

% (

0.04

, 0.

23).

Mig

liare

tti

et

al.

(200

4)

(Mig

liare

tti

andC

aval

lo,

2004

)

Tur

in,

Italy

, 1/

1997

-12

/199

9.

TS

P l

evel

s fo

r th

e pe

riod

sho

wn

in o

ne f

igur

e.

Thi

s st

udy

exam

ined

the

rel

atio

nshi

p be

twee

n T

SP

and

NO

2, a

nd h

ospi

talis

atio

n fo

r as

thm

a (I

CD

9: 4

93)

sepa

rate

ly f

or c

hild

ren

(<15

yea

rs)

adul

ts (

15-6

4 ye

ars)

and

eld

erly

(65

+ y

ear

s) i

n th

e ci

ty o

f T

urin

usi

ng a

cas

e-co

ntro

l de

sign

. O

vera

ll,

1,40

1 pa

tient

s re

side

nt

in

Tur

in

and

adm

itted

fo

r as

thm

a w

ere

de

fined

as

ca

ses;

20

1,07

1 pa

tient

s ad

mitt

ed f

or c

ause

s ot

her

tha

n re

spira

tory

di

seas

es

or

hear

t di

seas

es

wer

e de

fined

as

cont

rols

. P

erce

nt e

xces

s ris

ks w

ere

de

rived

by

mul

tiple

log

istic

reg

ress

ion

mod

els

adju

sted

fo

r se

x,

age,

ed

ucat

ion,

se

ason

ality

, te

mpe

ratu

re,

hum

idity

, so

lar

radi

atio

n,

day

of

wee

k an

d ho

liday

.

The

num

ber

of e

mer

genc

y ad

mis

sion

s fo

r re

spira

tory

ca

uses

si

gnifi

cant

ly

rose

w

ith

incr

ease

d e

xpos

ure

to

TS

P

and

NO

2,

part

icul

arly

am

ong

youn

g an

d el

derly

pa

tient

s fo

r bo

th

pollu

tant

s.

Afte

r m

utua

l ad

just

men

t fo

r bo

th

pollu

tant

s,

the

asso

ciat

ions

bec

ame

wea

ker

and

no m

ore

sign

ifica

nt.

Effe

cts

com

put

ed

for

10

µg/

m3

incr

emen

t of T

SP

: S

ingl

e-po

lluta

nt a

naly

sis:

T

otal

: 2.3

% (

1.1

, 3.6

) A

ge <

15: 1

.9%

(0.

4, 3

.4)

Age

15-

64: 2

.3%

NS

A

ge 6

5+: 8

.3%

(2.

9, 1

3.7)

T

wo-

pollu

tant

s an

alys

is

Tot

al: 0

.9%

NS

A

ge <

15: -

0.1

% N

S

Age

15-

64: 1

.2%

NS

A

ge 6

5+: 0

.9%

NS

.

Mig

liare

tti

et

al.

(200

5)

(Mig

liare

tti e

t al,

2005

)

Tur

in,

Italy

, 1/

1997

-12

/199

9.

Sam

e st

udy

as

abov

e,

incl

udin

g ad

ults

. T

SP

lev

els

for

the

perio

d sh

ow

n in

one

fig

ure.

Thi

s st

udy

exam

ined

the

rel

atio

nshi

p be

twee

n T

SP

and

NO

2, a

nd h

ospi

talis

atio

n fo

r as

thm

a (I

CD

9: 4

93)

in c

hild

ren

aged

<15

yea

rs i

n th

e ci

ty o

f T

urin

usi

ng a

cas

e-co

ntro

l des

ign.

On

the

basi

s of

the

prim

ary

diag

nos

is,

1,06

0 p

edia

tric

pa

tient

s re

sid

ent

in

Tur

in

and

adm

itted

fo

r as

thm

a w

ere

de

fined

as

ca

ses;

25

,52

3 ag

e-m

atch

ed p

atie

nts

adm

itted

for

cau

ses

oth

er th

an

resp

irato

ry

dise

ases

or

he

art

dise

ases

w

ere

defin

ed a

s co

ntro

ls.

Per

cent

exc

ess

risks

wer

e

deriv

ed b

y m

ultip

le l

ogis

tic r

egre

ssio

n m

odel

s af

ter

adju

stm

ent

for

1)

sex

and

age

, an

d 2

) af

ter

furt

her

allo

wa

nce

for

seas

onal

ity,

tem

pera

ture

, hu

mid

ity,

sola

r ra

diat

ion,

da

y of

w

eek

an

d ho

liday

. Lag

0-3

was

ap

pare

ntly

use

d.

The

num

ber

of e

mer

genc

y ad

mis

sion

s fo

r re

spira

tory

ca

uses

si

gnifi

cant

ly

rose

w

ith

incr

ease

d e

xpos

ure

to

TS

P

and

NO

2.

Con

side

ring

the

mul

tivar

iate

m

odel

, af

ter

mut

ual

adju

stm

ent

for

both

po

lluta

nts,

no

si

gnifi

cant

ass

ocia

tion

was

evi

dent

.

Effe

cts

com

put

ed

for

10

µg/

m3

incr

emen

t of T

SP

: S

ingl

e-po

lluta

nt a

naly

sis:

A

ge-s

ex

adju

sted

mod

el:

Tot

al: 2

.8%

(1

.7, 4

.0)

Age

<4:

2.3

% (

0.2,

3.4

) A

ge 4

-15:

3.1

% (

0.1,

4.8

) M

ultiv

aria

te m

odel

: T

otal

: 1.8

% (

0.3

, 3.2

) A

ge <

4: 1

.8%

(0.

0, 3

.5)

Age

4-1

5: 3

.0%

(0.

1, 5

.8)

Tw

o-po

lluta

nts

anal

ysis

A

ge-s

ex

adju

sted

mod

el:

Tot

al: 1

.4%

(1

.1, 4

.0)

Mul

tivar

iate

mod

el:

Tot

al: 0

.6%

(-0

.2, 3

.0)

report no. 4/11

135

SPA

IN

Ten

ías

et

al

(199

8)

(Ten

ias

et a

l, 19

98)

Stu

dy P

erio

d.:

94 -

95

Val

enci

a, S

pain

H

osp.

C

achm

ent

Pop

.:200

,000

B

S m

ean:

57.

7 B

S IQ

R: 2

5.6-

47.7

Ass

ocia

tions

be

twee

n ad

ult

(14+

ye

ars)

em

erge

ncy

asth

ma

emer

genc

y vi

sits

to

one

city

ho

spita

l (m

ean

=1.

0/da

y) a

nd B

S,

NO

2, O

3, S

O2

anal

yzed

us

ing

GLM

P

oiss

on

auto

-reg

ress

ive

mod

elin

g, a

fter

adju

stm

ent

for

wea

ther

se

ason

an

d tr

ends

usi

ng th

e A

PH

EA

pro

toco

l.

Ass

ocia

tion

with

ast

hma

was

pos

itive

and

m

ore

cons

iste

nt f

or N

O2

and

O3

than

for

BS

or

SO

2. T

he s

tudy

sug

gest

s th

at s

econ

dary

ox

idat

ive-

envi

ronm

ent

pollu

tant

s m

ay

be

mor

e as

thm

a re

leva

nt

than

pr

imar

y re

duct

ion-

envi

ronm

ent

pollu

tant

s (e

.g.,

carb

onac

eous

par

ticle

s).

NO

2 ha

d gr

eate

st

effe

ct o

n B

S i

n co

-pol

luta

nt m

odel

s, b

ut B

S

beca

me

sign

ifica

nt o

nce

1993

was

add

ed,

sh

ow

ing

pow

er

to

be

a lim

itatio

n of

th

is

stud

y.

Adu

lt A

sthm

a, B

S:

25

µg/

m3 ;

Lag

0:

For

199

3-19

95: 1

0.6%

(0.

9, 2

1.1)

F

or 1

994-

1995

: 6.4

% (

-4.8

, 18.

8).

Gal

an e

t al

(2

003)

(G

alan

et

al,

2003

) M

adrid

, S

pain

(1

995-

1998

).

Hos

pita

l C

atch

men

t P

opul

atio

n:55

5,00

0 P

M10

mea

n: 3

2.1.

Thi

s st

udy

show

s th

e as

soci

atio

ns

betw

een

emer

genc

y ro

om a

dmis

sion

for

ast

hma

to o

ne

city

ho

spita

l (m

ean

=3.

3/da

y)

in

Mad

rid,

and

PM

10 a

nd o

the

r co

-pol

luta

nts,

incl

udin

g N

O2,

O3,

an

d S

O2.

T

wo

anal

ytic

al

stra

tegi

es

wer

e

purs

ued:

1)

auto

regr

essi

ve P

oiss

on m

ode

ls a

nd

2)

GA

M

mod

els.

B

oth

the

mod

els

incl

uded

te

rms

for

lon

g-te

rm t

rend

s, s

easo

nalit

y, d

ay o

f w

eek,

hol

iday

, te

mpe

ratu

re,

hum

idity

, in

fluen

za

and

acut

e re

spira

tory

infe

ctio

ns.

Fur

ther

mod

els

incl

uded

var

ious

pol

lens

. La

g 0,

1,

2, 3

, 4

wer

e

cons

ider

ed.

Rel

ativ

e ris

ks o

f a

sthm

a em

erge

ncy

room

ad

mis

sion

s fo

r a

rise

in p

ollu

tant

leve

ls w

ere

syst

emat

ical

ly,

alth

ough

no

t al

way

s si

gnifi

cant

ly,

over

un

ity

for

PM

10

and

the

othe

r po

lluta

nts

, fo

r ea

ch

lag

used

, al

so

afte

r fu

rthe

r al

low

ance

for

var

ious

diff

ere

nt

type

rs o

f po

llen.

The

str

onge

st a

ssoc

iatio

ns

wer

e ob

serv

ed

at 1

day

lag

for

O3

and

3 da

ys

lag

for

the

rem

aini

ng

pollu

tan

ts.

Fur

ther

adj

ustm

ent

for

the

diffe

rent

typ

es o

f po

llen

did

not

sen

sibl

y m

odify

the

est

imat

es.

S

light

diff

eren

ces

wer

e ob

serv

ed b

etw

een

the

estim

ates

ob

tain

ed

with

pa

ram

etric

m

odel

ling

and

thos

e ob

tain

ed

with

G

AM

m

odel

s.

Effe

cts

on a

dm

issi

on f

or a

sthm

a co

mpu

ted

for

10 µ

g/m

3 inc

rem

ent

of P

M10

: La

g 0:

1.1

% (

-2.0

, 4.2

) La

g 1:

0.6

% (

-2.4

, 3.7

) La

g 2:

0.8

% (

-2.2

, 3.8

) La

g 3:

3.9

% (

1.0,

6.8

) La

g 4:

2.7

% (

-0.1

, 5.6

) A

fter

furt

her

adju

stm

ent

for

four

ty

pes

of p

olle

n;

Bes

t lag

(3)

: 4.5

% (

1.6,

7.4

) G

AM

mod

el; 5

.8 (

2.5,

9.1

).

GR

EEC

E

Kon

tos

et

al.

(199

9)

(Kon

tos

et a

l, 19

99)

Pira

eus,

A

the

ns

Gre

ece,

19

87-1

992)

B

S m

ean:

46.5

B

S m

ax:

200.

Rel

atio

n of

re

spira

tory

ho

spita

l ad

mis

sion

fo

r ch

ildre

n (0

-14

year

s.)

(mea

n =

4.3

/day

) to

BS

, S

O2,

N

O2,

an

d O

3 ev

alua

ted

usi

ng

a

nonp

aram

etric

st

ocha

stic

dy

nam

ical

sy

stem

ap

proa

ch a

nd f

requ

ency

do

mai

n an

alys

es.

Long

w

ave

an

d ef

fect

s of

w

eath

er

cons

ider

ed,

but

non-

linea

rity

and

inte

ract

ions

of

te

mp

erat

ure

and

RH

rel

atio

n w

ith H

A’s

no

t add

ress

ed.

Pol

lutio

n w

as

foun

d to

ex

plai

n si

gnifi

cant

po

rtio

n of

th

e H

A

varia

nce.

O

f po

lluta

nts

cons

ider

ed,

BS

w

as

con

sist

ently

am

ong

m

ost

stro

ngly

exp

lana

tory

pol

luta

nts

acro

ss

vario

us r

epor

ted

anal

yses

.

Ris

ks n

ot r

epo

rted

report no. 4/11

136

TAB

LE IV

. AC

UTE

PA

RTI

CU

LATE

MA

TTER

EXP

OSU

RE

AN

D R

ESPI

RA

TOR

Y M

EDIC

AL

VISI

TS (D

eriv

ed fr

om E

PA T

AB

LE 8

B-3

). Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

ode

ling

met

hods

: lag

s,

smoo

thin

g, c

o-po

lluta

nts

and

cova

riate

s.

Res

ults

and

Com

men

ts.

PM In

dex,

lag,

per

cent

exc

ess

risk%

(95%

LC

L, U

CL)

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Atk

inso

n et

al

. (1

999b

) (A

tkin

son

et a

l, 19

99b)

Lo

ndon

(92

- 9

4)

Pop

ulat

ion:

no

t rep

orte

d P

M10

Mea

n: 2

8.5

10th

-90t

h IQ

R: 1

5.8-

46.5

B

S m

ean:

12.7

10

th-9

0th

IQR

: 5.5

-21.

6.

All-

age

resp

irato

ry

(mea

n=90

/day

),

asth

ma

(25.

9/da

y),

and

othe

r re

spira

tory

(6

4.1/

day)

em

erge

ncy

doc

tor

(ED

) vi

sits

fro

m 1

2 Lo

ndon

ho

spita

ls

we

re

cons

ider

ed,

but

asso

ciat

ed

popu

latio

n si

ze

wa

s no

t re

port

ed.

Cou

nts

for

ages

0-1

4, 1

5-64

, an

d >

64 w

ere

also

exa

min

ed.

Poi

sson

GLM

reg

ress

ion

was

use

d, c

ontr

ollin

g fo

r se

ason

, da

y of

w

eek,

m

ete

orol

ogy,

au

toco

rrel

atio

n,

over

disp

ersi

on,

and

in

fluen

za

epid

emic

s.

PM

10 w

as p

ositi

vely

ass

ocia

ted,

but

not

BS

, fo

r al

l- ag

e/al

l-res

pira

tory

ca

tego

ry.

PM

10

resu

lts

wer

e dr

iven

by

sig

nific

ant

child

ren

and

youn

g ad

ult

asso

ciat

ions

, w

hile

old

er

adul

t vi

sits

ha

d ne

gativ

e (b

ut

non-

sign

ifica

nt)

PM

10-E

D v

isit

rela

tions

hip.

PM

10

wa

s po

sitiv

ely

asso

ciat

ed

for

all

age

s,

child

ren,

and

you

ng a

dults

for

ast

hma

ED

vi

sits

. H

ow

eve

r,

PM

10-a

sth

ma

rela

tions

hip

coul

d no

t be

sep

arat

ed f

rom

SO

2 in

mul

ti-

pollu

tant

reg

ress

ions

. O

lde

r ad

ult

ED

vis

its

mos

t st

rong

ly a

ssoc

iate

d w

ith C

O.

No

O3-

ED

vis

its r

ela

tions

hips

was

fou

nd (

but

no

war

m s

easo

n an

alys

es a

ttem

pted

).

PM

10 (

50 µ

g/m

3 ) N

o co

-pol

luta

nt:

All

Re

spira

tory

ED

vis

its

All

age

(lag

1):

4.9%

(1.

3, 8

.6)

<15

(la

g 2)

: 6.4

% (

1, 1

2.2)

15

-64

(lag

1): 8

.6%

(3.

4, 1

4)

Ast

hma

ED

vis

its

All

age

(lag

1):

8.9%

(3,

15.

2)

<15

(la

g 2)

: 12.

3% (

3.4,

22)

15

-64

(lag

1): 1

3% (

4.6,

22.

1)

PM

10

(50

µg

/m3 );

la

g 2

&

co-

pollu

tant

; ch

ildre

n’s

PM

al

one:

12

.3%

(3.

4, 2

2)

& N

O2:

7.8

% (

-1.2

, 17.

6)

& O

3: 1

0.5

% (

1.6,

20.

1)

& S

O2:

8.1

% (

-1.1

, 18.

2)

& C

O: 1

2.1

% (

3.2,

21.

7).

Haj

at e

t al

. (1

999)

(H

ajat

et

al,

1999

) Lo

ndon

, E

ngla

nd,

1992

-19

94.

Pop

ulat

ion:

28

2,00

0 P

M10

mea

n: 2

8.2

PM

10 1

0-90

th%

=16

.3-4

6.4

B

S m

ean:

10.

1 B

S 1

0t-9

0th%

=4.

5-15

.9

Thi

s st

udy

exa

min

ed a

ssoc

iatio

ns o

f P

M1

0, B

S,

NO

2,

O3,

S

O2,

an

d C

O,

with

pr

imar

y ca

re

gene

ral

prac

titio

ner

asth

ma

and

othe

r lo

wer

re

spira

tory

di

seas

es

(LR

D)

cons

ulta

tions

. A

sthm

a co

nsu

ltatio

n m

eans

per

day

= 3

5.3

(all

ages

); 1

4.(0

-14

year

s,);

17.

7 (1

5-64

yea

rs.)

; 3.

6 (>

64

year

s.).

LR

D

mea

ns

=

155

(all

ages

);

39.7

(0-1

4 ye

ars,

);

73.8

(1

5-64

ye

ars.

);

41.1

(>

64

year

s.).

T

ime-

serie

s an

alys

es

of

daily

nu

mbe

rs o

f co

nsul

tatio

ns p

erfo

rmed

, co

ntro

lling

fo

r tim

e tr

ends

, se

ason

fac

tors

, da

y of

wee

k,

influ

enza

, w

eat

her,

po

llen

leve

ls,

and

seria

l co

rrel

atio

n.

Pos

itive

ass

ocia

tions

, w

eakl

y si

gnifi

cant

and

co

nsis

tent

acr

oss

lags

, ob

serv

ed b

etw

een

asth

ma

cons

ulta

tions

and

NO

2 an

d C

O i

n ch

ildre

n,

and

w

ith

PM

10

in

adul

ts,

and

betw

een

othe

r LR

D c

onsu

ltatio

ns a

nd S

O2

in

child

ren.

A

utho

rs

con

clud

ed

that

th

ere

are

asso

ciat

ions

bet

wee

n a

ir po

llutio

n an

d da

ily c

once

ntra

tions

for

ast

hma

and

oth

er

low

er

resp

irato

ry

dise

ase

in

Lo

ndon

. In

ad

ults

, th

e au

thor

s co

nclu

ded

tha

t th

e on

ly

cons

iste

nt

ass

ocia

tion

was

w

ith

PM

10.

Acr

oss

all

of t

he v

ario

us a

ge,

caus

e, a

nd

seas

on

cate

gor

ies

cons

ide

red,

P

M10

w

as

the

pollu

tant

m

ost

cohe

rent

in

gi

ving

po

sitiv

e po

lluta

nt

RR

es

timat

es

for

both

as

thm

a an

d ot

her

LRD

(11

of

12 c

ateg

orie

s po

sitiv

e)

in

sing

le

pollu

tant

m

odel

s co

nsid

ered

.

Ast

hma

Doc

tor’s

Vis

its

50 µ

g/m

3 PM

10

-Yea

r-ro

und,

Sin

gle

Pol

luta

nt:

All

ages

(la

g 2

): 5

.4%

(-0

.6, 1

1.7)

0-

14 (

lag

1): 6

.4%

(-1

.5, 1

4.6)

15

-64

(lag

0): 9

.2%

(2.

8, 1

5.9)

>

64 (

lag

2): 1

1.7%

(-1

.8, 2

6.9

) -Y

ear-

roun

d, 2

Pol

luta

nt,

Chi

ldre

n (0

-14)

: (la

g 1)

PM

10:

W/ N

O2:

0.8

% (

-8.7

, 11.

4)

W/ O

3: 5

.5%

(-2

.1, 1

3.8)

W

/ SO

2: 3

.2%

(-6

.4, 1

3.7)

O

ther

LR

D; 5

0 µ

g/m

3 PM

10

-Yea

r-ro

und,

Sin

gle

Pol

luta

nt:

All

ages

(la

g 2

): 3

.5%

(0,

7.1

) 0-

14 (

lag

1): 4

.2%

(-1

.2, 9

.9)

15-6

4 (la

g 2)

: 3.7

% (

0.0,

7.6

) >

64yr

s.(la

g 2)

: 6.2

% (

0.5,

12

.9).

report no. 4/11

137

Haj

at e

t al

. (2

001)

(H

ajat

et

al,

2001

) Lo

ndon

,199

2-19

94.

44,4

06-4

9,59

6 re

gist

ered

pa

tient

s <

1 to

14

year

s.

PM

10 m

ean

28.5

(13

.9)

Dai

ly p

hysi

cia

n co

nsul

tatio

ns

(mea

n da

ily 4

.8 f

or

child

ren;

15

.3

for

adul

ts)

for

alle

rgic

rh

initi

s (I

CD

9:

477)

, S

O2,

O

3,

NO

2,

CO

, P

M1

0,

and

polle

n us

ing

gene

raliz

ed a

dditi

ve m

odel

s w

ith

nonp

aram

etric

sm

ooth

er.

SO

2 an

d O

3 sh

ow s

tron

g as

soci

atio

ns w

ith

the

num

ber

of

cons

ulta

tions

fo

r al

lerg

ic

rhin

itis.

Est

imat

es l

arge

st f

or a

lag

of

3 or

4

days

prio

r to

con

sulta

tions

, w

ith c

umul

ativ

e m

easu

res

stro

nger

th

an

sing

le

day

lag

s.

Str

onge

r ef

fect

s w

ere

foun

d fo

r ch

ildre

n th

an a

dults

. T

he t

wo-

po

lluta

nt a

naly

sis

of

the

child

ren’

s m

odel

sho

we

d th

at P

M10

and

N

O2

asso

ciat

ions

dis

appe

are

d on

ce e

ither

S

O2

or O

3 w

as in

corp

orat

ed in

to th

e m

odel

.

PM

10 -

Incr

emen

t (10

-90%

)

(15.

8-46

.5)

Age

<1-

14 y

ear

s la

g 3:

10.

4 (2

.0 to

19.

4)

Cum

0-3

: 17.

4 (6

.8 to

29.

0)

Age

s 15

-64

year

s la

g 2:

7.1

(2.

6 to

11.

7)

Cum

0-6

: 20.

2 (1

4.1

to 2

6.6)

report no. 4/11

138

Haj

at e

t al

. (2

002)

(H

ajat

et

al,

2002

) Lo

ndon

, 199

2-19

94.

268,

718-

295,

740

regi

ster

ed p

atie

nts.

P

M10

mea

n 28

.5 (

13.7

).

BS

mea

n 12

.7 (

7.9)

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

daily

phy

sici

an

cons

ulta

tion

s (m

ean

daily

4.8

for

ch

ildre

n; 1

5.3

for

adu

lts)

for

uppe

r re

spira

tory

di

seas

es,

exc

ludi

ng a

llerg

ic r

hini

tis (

ICD

9:46

0-46

3,,

465,

47

0-47

5),

and

PM

10,

BS

, S

O2,

O3,

N

O2,

C

O,

usi

ng

GA

Ms

with

no

npar

am

etric

sm

ooth

ers

to c

ontr

ol f

or s

eas

onal

pat

tern

s. T

he

mod

els

wer

e

furt

her

adju

sted

fo

r da

y of

th

e

wee

k,

holid

ay,

in

fluen

za,

wea

ther

, po

llen

conc

entr

atio

ns

and

seria

l co

rrel

atio

n.

Lag

0, l

ag1,

lag

2, l

ag3

we

re c

onsi

dere

d. T

he

mos

t si

gnifi

cant

ly a

ssoc

iate

d la

g, r

egar

dles

s of

w

heth

er

the

as

soci

atio

n

was

po

sitiv

e or

ne

gativ

e, w

as s

how

n.

Hig

her

leve

ls o

f S

O2

incr

ease

d nu

mbe

rs o

f ch

ildho

od

cons

ulta

tion.

S

tron

ger

asso

ciat

ions

wer

e f

ound

with

PM

10

and

BS

in

adu

lts a

ged

15-

64 a

nd i

n a

dults

age

d 65

an

d ov

er,

also

afte

r fu

rthe

r ad

just

men

t fo

r ot

her

co-p

ollu

tant

s. I

n ge

nera

l, as

soci

atio

ns

wer

e st

rong

est

in e

lder

ly p

eopl

e, w

eake

st in

th

e ch

ildre

n, a

nd w

ere

larg

ely

foun

d in

the

w

inte

r m

onth

s fo

r th

ese

two

ag

e gr

oups

, an

d in

the

su

mm

er m

onth

s fo

r ad

ults

ag

ed

15-6

4.

An

ap

pare

nt

decr

ease

in

co

nsul

tatio

ns

was

as

soci

ated

in

co

lder

m

onth

s w

ith O

3 fo

r al

l ag

es

and

with

BS

in

child

ren.

PM

10 -

Incr

emen

t (10

-90%

)

(16-

47 µ

g/m

3 ) A

ll ye

ar:

Age

0-1

4:

2.0%

(-0

.2, 4

.2)

adju

stm

ent

NO

2: 2

.0%

(-0

.2, 4

.2)

adju

stm

ent O

3: 1

.8%

(-0

.4, 3

.9)

adju

stm

ent S

O2:

2.0

% (

-0.6

, 4.6

) A

ge 1

5-64

:

5.7%

(2.

9, 8

.6)

adju

stm

ent

NO

2: 2

.8%

(0.

7, 4

.9)

adju

stm

ent O

3: 4

.8%

(2.

6, 7

.0)

adju

stm

ent S

O2:

4.8

% (

2.2,

7.5

) A

ge 6

5+:

10

.2%

(5.

3, 1

5.3)

ad

just

men

t N

O2:

4.6

% (

0.5,

8.8

) ad

just

men

t O3: 1

0.7%

(5.

7, 1

6.0)

ad

just

men

t S

O2:

10

.6%

(4

.5,

17.1

) W

arm

sea

son:

A

ge 0

-14:

1.1

% (

-2.4

, 4.8

) A

ge 1

5-64

: 6.0

% (

2.7,

9.4

) A

ge 6

5+: 0

.1%

(-7

.7, 8

.5)

Col

d se

ason

A

ge 0

-14:

2.7

% (

-0.1

, 5.5

) A

ge 1

5-64

: 3.6

% (

1.0,

6.4

) A

ge 6

5+: 1

8.9

% (

11.7

, 26.

7)

BS

- In

crem

ent (

10-9

0%)

(6

-22

µg/

m3 )

All

year

: A

ge 0

-14:

-2.

4% (

-4.4

, -0.

3)

Age

15-

64: 3

.5%

(0.

6, 6

.4)

Age

65+

: 8.8

% (

4.6,

13.

3)

War

m s

easo

n:

Age

0-1

4: 3

.5%

(0.

3, 6

.9)

Age

15-

64: 6

.6%

(3.

6, 9

.6)

Age

65+

: 2.8

% (

-3.9

, 10.

1)

Col

d se

ason

A

ge 0

-14:

-3.

3% (

-6.0

, -0.

6)

Age

15-

64: 1

.5%

(-0

.9, 4

.1)

Age

65+

: 9.9

% (

3.7,

16.

3).

report no. 4/11

139

FRA

NC

E

Med

ina

et

al.

(199

7)

(Med

ina

et a

l, 19

97)

Gre

ater

Par

is,

1991

-199

5 P

opul

atio

n: 6

.5 M

M

Mea

n P

M13

: 25

PM

13 m

in/m

ax:

6/9

5 M

ean

BS

: 21

B

S m

in/m

ax:

3/1

30.

Thi

s st

udy

eva

luat

ed

shor

t-te

rm

rela

tions

hips

be

twee

n P

M13

an

d B

S

conc

entr

atio

ns

and

doct

ors'

hou

se c

alls

(m

ean

=8/

day;

20

% o

f ci

ty

tota

l) in

Gre

ater

Par

is.

Poi

sson

reg

ress

ion

used

, w

ith

non-

para

met

ric

smoo

thin

g fu

nct

ions

co

ntro

lling

fo

r tim

e tr

end,

se

ason

al

patt

erns

, po

llen

coun

ts,

influ

enza

ep

idem

ics,

day

of

wee

k,

holid

ays,

and

wea

ther

.

A r

elat

ions

hip

betw

een

all a

ge (

0-64

yea

rs.)

as

thm

a ho

use

calls

an

d P

M13

, B

S,

SO

2,

NO

2,

and

O3

air

pollu

tion,

es

peci

ally

fo

r ch

ildre

n ag

ed 0

-14

year

s (m

ean

= 2

/day

). I

n tw

o-po

lluta

nt

mod

els

incl

udin

g B

S

with

, su

cces

sive

ly,

SO

2, N

O2,

and

O3,

onl

y B

S

and

O3

effe

cts

rem

aine

d st

able

. T

hese

re

sults

al

so

indi

cate

th

at

air

pollu

tant

as

soci

atio

ns n

oted

for

hos

pita

l ED

vis

its a

re

also

app

licab

le t

o a

wid

er p

opul

atio

n th

at

visi

ts th

eir

doct

or.

Doc

tor’s

Ast

hm

a H

ouse

Vis

its:

50 µ

g/m

3 13

P

M Y

ear-

roun

d, S

ingl

e P

ollu

tant

: A

ll ag

es (

lag

2):

12.

7% (

4.1,

21.

9)

0-14

(la

g 0-

3): 4

1.5%

(20

, 66.

8)

15-6

4 (la

g 2)

: 6.3

% (

-4.6

, 18

.5).

ITA

LY

Veg

ni e

t al

. (2

005)

(V

egni

et

al,

2005

) C

omo,

Ital

y 19

95-1

997.

P

opul

atio

n.=

~85

,000

M

ean

TS

P=

62.

4 (2

8.6)

.

Thi

s st

udy

eval

uate

d re

spira

tory

dr

ug

disp

ensi

ng

dat

a as

he

alth

in

dica

tors

fo

r th

e ef

fect

s of

TS

P.

Wee

kly

air

mea

n co

ncen

trat

ions

of

TS

P w

ere

mod

eled

with

: 1)

wee

kly

coun

t of

in

divi

dual

s ha

ving

had

at

leas

t on

e re

spira

tory

dr

ug d

ispe

nse

d (c

ases

) an

d 2

) to

tal w

eek

ly s

um

of

daily

de

fined

do

ses

(DD

D)

of

resp

irato

ry

drug

s di

spen

sed.

A P

ois

son

regr

essi

on m

odel

ad

just

ed

for

long

-ter

m

tren

ds,

seas

onal

va

riatio

ns, h

olid

ays,

and

wea

ther

was

use

d.

Sig

nific

ant

dire

ct a

ssoc

iatio

ns b

etw

een

TS

P

and

both

ca

ses

and

DD

D

wer

e fo

und.

A

utho

rs

conc

lude

d th

at

both

ca

ses

and

DD

D o

f di

spe

nsed

res

pira

tory

dru

gs c

oul

d be

use

ful

for

epid

emio

logi

cal

surv

eilla

nce

of

air

pollu

tant

hea

lth e

ffect

s.

Exc

ess

risk

for

a va

riatio

n fr

om

10th

to

90

th

perc

entil

e of

T

SP

(2

9-92

µg/

m3 ):

C

ases

: 8.2

% (

0.2,

16.

9)

DD

D: 1

3.7

% (

4.4,

23.

8).

SPA

IN

Dam

iá

et

al.

(199

9)

(de

Die

go D

amia

et a

l, 19

99)

Val

enci

a,

Sp

ain,

3/

1994

-3/

1995

).

BS

mea

n: 1

01

BS

ran

ge: 3

4-21

3.

Ass

ocia

tions

of

BS

and

SO

2 w

ith w

eekl

y to

tal

ED

adm

issi

ons

for

asth

ma

pat

ient

s ag

ed >

12

year

s (m

ean

= 1

0/w

eek)

at

one

hosp

ital

over

on

e ye

ar a

sses

sed,

usi

ng l

inea

r st

epw

ise

GLM

re

gres

sion

. S

easo

n-sp

ecifi

c an

alys

es d

one

for

ea

ch

of

4 se

ason

s,

but

no

othe

r lo

ng-

wav

e

cont

rols

. Lin

ear

T, R

H,

BP

, ra

in, a

nd w

ind

spe

ed

incl

uded

as

crud

e w

eath

er c

ontr

ols

in A

NO

VA

m

odel

s.

Bot

h B

S

and

SO

2 co

rrel

ated

w

ith

ED

ad

mis

sion

s fo

r as

thm

a (S

O2:

r=

0.32

; B

S:

r=0.

35),

but

onl

y B

S s

igni

fican

t in

ste

pw

ise

mul

tiple

re

gres

sion

. N

o lin

ear

rela

tions

hip

foun

d w

ith

wea

ther

va

riabl

es.

Str

atifi

ed

AN

OV

A f

ound

str

onge

st B

S-E

D a

ssoc

iatio

n in

the

aut

umn

and

durin

g ab

ove

aver

age

tem

pera

ture

s.

Unc

ontr

olle

d

auto

corr

elat

ion

(e.g

., w

ithin

-sea

son)

an

d w

eath

er

effe

cts

likel

y re

mai

n in

mod

els.

Ast

hma

ED

Vis

its (

all a

ges)

: B

S: 4

0 µ

g/m

3 (si

ngle

pol

luta

nt)

BS

as

a la

g 0

we

ekly

ave

rage

: 41

.5%

(39

.1,

43.9

).

report no. 4/11

140

GR

EEC

E

Pan

tazo

poul

ou

et

al.

(199

5) (

Pan

tazo

poul

ou e

t al

, 199

5)

Ath

ens,

Gre

ece,

198

8.

Win

ter

(1/8

8-3/

88,9

/88-

12/8

8)

BS

mea

n.:7

5

BS

5-9

5th %

=2

6 -

161

Sum

mer

(3

/22/

88-

3/88

,9/2

1/88

) B

S m

ean.

:55

B

S 5

-95th

%=

19

- 90

Thi

s st

udy

exam

ined

effe

cts

of a

ir po

llutio

n on

da

ily

emer

genc

y ou

tpat

ient

vi

sits

an

d ad

mis

sion

s fo

r ca

rdia

c an

d r

espi

rato

ry c

ause

s.

Air

pollu

tant

s in

clud

ed:

BS

, C

O,

and

N

O2.

M

ultip

le

linea

r G

LM

regr

essi

on

mod

els

used

, co

ntro

lling

for

lin

ear

effe

cts

of t

empe

ratu

re a

nd

RH

, da

y of

w

eek,

ho

liday

s,

and

dum

my

varia

bles

fo

r m

onth

to

cr

udel

y co

ntro

l fo

r se

ason

, sep

arat

ely

for

win

ter

and

sum

mer

.

Dai

ly

num

ber

of

emer

genc

y vi

sits

re

late

d po

sitiv

ely

with

eac

h ai

r po

lluta

nt,

but

only

re

ache

d no

min

al

leve

l of

st

atis

tical

si

gnifi

canc

e fo

r N

O2

in w

inte

r. H

owev

er,

the

very

lim

ited

time

for

each

w

ithin

-sea

son

anal

ysis

(6

m

o.)

undo

ubta

bly

limite

d

the

pow

er o

f th

is a

naly

sis

to d

etec

t si

gnifi

cant

ef

fect

s.

Als

o,

poss

ible

la

gged

po

llutio

n ef

fect

s w

ere

ap

pare

ntly

no

t in

vest

igat

ed,

wh

ich

may

ha

ve r

educ

ed e

ffect

est

imat

es.

Sin

gle

Pol

luta

nt M

odel

s F

or W

inte

r (B

S: 2

5 µ

g/m

3 ) O

utpa

tient

Ho

spita

l Vis

its:

1.

1% (

-0.7

, 2.3

) R

espi

rato

ry h

ospi

tal a

dmis

sion

s:

4.3%

(0.

2, 8

.3)

For

Sum

mer

(B

S: 2

5 µ

g/m

3 )

Out

patie

nt H

osp

ital V

isits

0.

6% (

-4.7

, 6.0

) R

espi

rato

ry h

ospi

tal a

dmis

sion

s:

5.5%

(-3

.6, 1

4.7

)

BO

SNIA

H

astin

gs

et

al.

(200

2)

(Has

tings

an

dJar

dine

, 20

02)

Sol

dier

s de

ploy

ed

to

Bos

nia

1997

-199

8.

Mea

n P

M10

m

axim

um

leve

l: 92

.9

Mea

n P

M10

ave

rage

leve

l: 75

.5.

Thi

s ec

olog

ic s

tudy

was

con

duct

ed t

o de

term

ine

the

rela

tion

betw

een

we

ekly

lev

els

of P

M10

and

w

eekl

y up

per

resp

irato

ry

dise

ase

rate

s in

so

ldie

rs d

eplo

yed

to B

osni

a in

199

7-19

98.

PM

10

max

imum

leve

l was

def

ined

as

the

high

est

PM

10

leve

l re

cord

ed a

t ca

mp

durin

g a

give

n w

eek,

P

M10

ave

rage

lev

el w

as d

efin

ed a

s th

e av

erag

e of

all

read

ings

tak

en a

t a

cam

p du

ring

a gi

ven

wee

k.

Whe

n al

l ca

mps

wer

e co

mb

ined

, th

ere

was

a

stat

istic

ally

si

gnifi

cant

as

soci

atio

n be

twee

n th

e

PM

10

ma

xim

um

leve

l an

d up

per

resp

irato

ry

trac

t ra

tes

base

d on

K

rusk

al-W

allis

an

d M

ann-

Whi

tney

U

te

sts

(p=

0.04

7),

and

the

Pea

rson

cor

rela

tion

was

st

atis

tical

ly

sign

ifica

nt

(p=

0.0

41).

A

lthou

gh

the

rela

tion

was

not

sta

tistic

ally

sig

nific

ant

in

anal

yses

co

nduc

ted

on

the

indi

vidu

al

cam

ps,

the

aver

age

rate

in

crea

sed

with

ea

ch q

uart

ile o

f P

M10

ma

xim

um e

xpos

ure.

T

here

w

as

no

stat

istic

ally

si

gnifi

cant

as

soci

atio

n

bet

we

en

PM

10

aver

age

leve

l an

d up

per

resp

irato

ry

dise

ase

rate

s,

alth

ough

th

e av

erag

e ra

te

incr

ease

d w

ith

each

qua

rtile

of P

M10

ave

rage

exp

osu

re.

No

risk

sho

wn

ISR

AEL

G

arty

et

al.

(199

8) (

Gar

ty

et a

l, 19

98)

Tel

Avi

v, Is

rae

l, 19

93.

PM

10 m

ean:

45.

Sev

en d

ay r

unni

ng m

ean

of a

sthm

a E

D v

isits

by

child

ren

(1-1

8 ye

ars)

to

a

pedi

atric

ho

spita

l m

odel

ed in

rel

atio

n to

PM

10 in

Tel

Avi

v, Is

rael

.

No

PM

10 a

sso

ciat

ions

fou

nd w

ith E

D v

isits

. T

he

ER

vi

sits

–pol

luta

nt

corr

elat

ion

incr

ease

d si

gni

fican

tly w

hen

the

Sep

tem

ber

peak

w

as

exc

lude

d.

Use

of

a

wee

k-lo

ng

aver

age

and

asso

ciat

ed u

nco

ntro

lled

long

-w

ave

flu

ctua

tions

(w

ith

resu

ltant

au

toco

rrel

atio

n) l

ikel

y pr

even

ted

mea

ning

ful

anal

yses

of

sh

ort

–ter

m

PM

as

soci

atio

ns

with

ED

vis

its.

No

risks

sho

wn

report no. 4/11

141

TAB

LE V

– L

ON

G-T

ERM

PA

RTI

CU

LATE

MA

TTER

EXP

OSU

RE

AN

D M

OR

TALI

TY.

Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

etho

ds, c

o-p

ollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

. PM

Inde

x, R

R (9

5% C

I)

Subn

atio

nal s

tudi

es

N

OR

WA

Y

Nae

ss e

t al

., 20

07 (

Nae

ss

et a

l, 20

07)

Coh

ort

of

all

inha

bita

nts

of O

slo

(143

,842

).

Fol

low

-up

perio

d:

1992

-19

98.

PM

2.5

rang

e: 6

.56-

22.3

4

PM

10 r

ange

: 6.5

7-30

.13

Thi

s st

udy

inve

stig

ated

the

ass

ocia

tion

betw

een

conc

entr

atio

ns

of P

M10

, P

M2.

5 an

d N

O2

in 1

992-

1995

, an

d

caus

e-sp

ecifi

c m

orta

lity.

T

he

popu

latio

n in

clud

ed

all

inha

bita

nts

of

Osl

o N

orw

ay,

aged

51

–90

year

s on

Ja

nuar

y 19

92

with

fol

low

-up

of

deat

hs f

rom

199

2 to

199

8. A

n ai

r di

sper

sion

m

odel

w

as

used

to

es

timat

e le

vels

of

e

xpos

ure

in

all

470

adm

inis

trat

ive

neig

hbou

rhoo

ds.

Co

x pr

opor

tiona

l ha

zard

s re

gres

sion

m

odel

s w

ere

use

d af

ter

adju

stm

ent

for

age,

edu

catio

n an

d oc

cupa

tiona

l cl

ass.

To

mod

el t

he r

elat

ion

betw

een

air

pollu

tant

s an

d m

orta

lity,

G

AM

m

odel

s w

ere

used

.

Som

e di

rect

as

soci

atio

ns

wer

e ob

serv

ed

betw

een

NO

2, P

M10

and

PM

2.5,

and

mor

talit

y fo

r al

l cau

ses,

CV

D,

lung

ca

ncer

, bu

t m

ainl

y C

OP

D.

Incr

eas

ed

risks

fo

r to

tal

mor

talit

y w

ere

str

onge

r fo

r su

bjec

ts a

ged

51-7

0 ye

ars

th

an in

old

er s

ubje

cts.

Am

ong

the

limita

tions

of

th

is

stud

y,

ther

e is

an

in

adeq

uate

al

low

ance

for

cova

riate

s, in

clud

ing

smok

ing

T

he t

hree

pol

luta

nts

shar

ed s

imila

r re

sults

, be

ing

thei

r co

rrel

atio

ns h

igh

(bet

wee

n 0.

88

and

0.95

).

Occ

upat

iona

l cl

ass

and

edu

catio

n ad

just

ed

HR

fo

r th

e 4th

vs

1st

qu

artil

e of

exp

osur

e to

PM

2.5:

All

caus

e m

orta

lity

Men

51

-70

year

s:

1.44

(1

.32,

1.

58)

Wom

en 5

1-70

yea

rs:

1.41

(1.

27,

1.43

) M

en

71-9

0 ye

ars:

1.

18

(1.1

0,

1.26

) W

omen

71-

90 y

ears

: 1.

11 (

1.05

, 1.

17)

CV

D

(qua

rtile

in

crea

se

of

expo

sure

) M

en

51-7

0 ye

ars:

1.

10

(1.0

5,

1.16

) W

omen

51-

70 y

ears

: 1.

14 (

1.06

, 1.

21)

Men

71

-90

year

s:

1.05

(1

.01,

1.

08)

Wom

en 7

1-90

yea

rs:

1.03

(1.

00,

1.05

) C

OP

D

(qua

rtile

in

crea

se

of

expo

sure

) M

en 5

1-70

yea

rs:

1.27

(1

.11,

1.4

7)

Wom

en 5

1-70

yea

rs:

1.09

(0.

94,

1.25

) M

en

71-9

0 ye

ars:

1.

10

(1.0

0,

1.21

) W

omen

71-

90 y

ears

: 1.

05 (

0.96

, 1.

16)

report no. 4/11

142

Lu

ng c

ance

r (q

uart

ile i

ncre

ase

of

expo

sure

) M

en

51-7

0 ye

ars:

1.

07

(0.9

7,

1.18

) W

omen

51-

70 y

ears

: 1.

27 (

1.13

, 1.

43)

Men

71

-90

year

s:

1.07

(0

.97,

1.

18)

Wom

en 7

1-90

yea

rs:

1.16

(1.

02,

1.32

) S

imila

r re

sults

w

ere

show

n fo

r P

M10

.

SW

EDEN

Ros

enlu

nd

et

al.

(200

6)

(Ros

enlu

nd e

t al

, 200

6)

Sto

ckol

m,

Sw

eden

,199

2-19

94.

Cas

e-co

ntro

l stu

dy

Sub

ject

s: 2

72 c

ases

with

fa

tal

myo

card

ial

infa

rctio

n

and

1,87

0 ho

spita

l co

ntro

ls.

30

year

re

side

ntia

l P

M10

ex

posu

re,

med

ian:

2.6

for

ca

ses

(incl

udin

g no

n-fa

tal

case

s)

and

2.4

for

cont

rols

.

Thi

s ca

se-c

ontr

ol

stud

y ex

amin

ed

the

asso

ciat

ion

bet

we

en 3

0 ye

ar a

vera

ge e

xpos

ure

to P

M10

, an

d ot

her

co-p

ollu

tant

s, i

nclu

din

g S

O2,

N

O2

and

CO

, an

d fir

st e

piso

de o

f fa

tal w

ithin

28

days

(an

d no

n-fa

tal)

myo

card

ial

infa

rctio

n (M

I).

The

ann

ual

mea

n le

vel

of P

M10

was

ass

esse

d on

ly f

or t

he y

ear

2000

, th

us a

ssum

ing

cons

tant

le

vels

dur

ing

the

stud

y pe

riod.

The

air

pollu

tion

da

ta f

or e

ach

year

was

lin

ked

to t

he h

isto

ry o

f re

side

nce

of e

ach

subj

ect

for

the

corr

espo

ndin

g ye

ar f

rom

19

60 t

o st

udy

incl

usio

n. O

Rs

wer

e de

rived

by

mul

tiple

log

istic

reg

ress

ion

mod

els

afte

r ad

just

men

t fo

r ag

e,

sex,

h

ospi

tal

catc

hmen

t ar

ea,

smok

ing,

ph

ysic

al

activ

ity,

diab

etes

and

soc

ioec

onom

ic s

tatu

s. E

stim

ates

fo

r P

M2.

5 w

ere

no

t sh

ow

n,

give

n th

e

high

co

rrel

atio

n in

thi

s sa

mpl

e be

twee

n P

M2.

5 an

d P

M10

(r=

0.99

8).

PM

10 w

as n

ot s

igni

fican

tly a

ssoc

iate

d w

ith

risk

of

fata

l M

I. A

bo

rder

line

sign

ifica

nt

exce

ss r

isk

was

fou

nd f

or “

out

of h

ospi

tal

deat

h”.

Sim

ilar

patte

rns

of r

isk

wer

e fo

und

fo

r N

O2,

CO

, an

d S

O2.

RR

for

an

incr

emen

t of

5 μ

g/m

3

(95th

–

5th

perc

entil

e)

of

PM

10.

Mor

talit

y w

ithin

28

da

ys

from

ad

mis

sion

to h

ospi

tal:

Tot

al d

eath

s: 1

.39

(0.9

4, 2

.07)

In

-hos

pita

l de

aths

: 1.

21

(0.7

5,

1.94

) O

ut-o

f-ho

spita

l de

aths

: 1.

84

(1.0

0, 3

.0).

report no. 4/11

143

THE

NET

HER

LAN

DS

H

oek

et a

l. (2

002)

(H

oek

et a

l, 20

02)

The

N

ethe

rland

s,

1986

-19

94

Coh

ort s

tudy

S

ubje

cts:

4,4

92

BS

exp

osur

e, m

ean

(SD

):

back

grou

nd

15.1

(2

.5);

ba

ckgr

ound

an

d lo

cal

15.5

(3.

2).

This

stud

y ex

amin

ed th

e as

soci

atio

n be

twee

n B

S an

d N

O2 i

n a

coho

rt of

4,4

92 re

side

nts i

n va

rious

are

as o

f th

e N

ethe

rland

s and

cau

se-s

peci

fic m

orta

lity.

Lo

ng-t

erm

ex

posu

re

to

tra

ffic-

rela

ted

BS

an

d

NO

2 w

as e

stim

ated

for

the

198

6 ho

me

addr

ess.

T

he

asso

ciat

ion

betw

een

ex

posu

re

to

air

pollu

tion

and

to

tal,

card

iopu

lmon

ary

and

non-

card

iopu

lmon

ary,

non

-lung

can

cer

mor

talit

y w

as

asse

ssed

w

ith

Co

x’s

prop

ortio

nal

haz

ards

m

odel

s,

afte

r ad

just

men

t fo

r ag

e,

sex,

ed

ucat

ion,

BM

I, oc

cupa

tion,

act

ive

and

pass

ive

ci

gare

tte

smok

ing,

an

d ne

ighb

ourh

ood

soci

oeco

nom

ic s

core

. T

wo

mod

els

of e

xpos

ure

for

ever

y po

lluta

nt

we

re

used

: 1

) th

e ba

ckgr

ound

co

ncen

trat

ion

wa

s en

tere

d in

th

e m

odel

with

the

indi

cato

r va

riabl

e fo

r liv

ing

near

a

maj

or r

oad.

2)

the

sum

of

the

back

grou

nd

and

the

estim

ated

co

ntrib

utio

n fr

om

livin

g n

ear

a m

ajor

roa

d to

air

pollu

tion

conc

entr

atio

ns.

Too

fe

w p

eopl

e di

ed f

rom

res

pira

tory

dis

orde

rs a

nd

lung

can

cer

to o

btai

n st

able

est

imat

es f

or t

he

indi

cato

r va

riabl

e fo

r liv

ing

nea

r a

maj

or r

oad.

Ove

rall,

48

9 de

aths

oc

curr

ed

durin

g th

fo

llow

-up

perio

d. C

ardi

opul

mon

ary

mor

talit

y w

as

sign

ifica

ntly

ass

ocia

ted

with

liv

ing

near

a

maj

or

road

, le

ss

cons

iste

ntly

w

ith

the

estim

ated

bac

kgro

und

conc

entr

atio

n. O

ther

ca

uses

of

de

ath,

in

clud

ing

lung

ca

ncer

, w

ere

unre

late

d to

air

pollu

tion.

RR

for

an

incr

emen

t of

10

(95

th –

5th

per

cent

ile)

of B

S.

All

caus

e m

orta

lity

Bac

kgro

und

U

nadj

uste

d: 1

.37

(0.9

5, 1

.97)

A

djus

ted:

1.1

7 (

0.76

, 1.7

8)

Adj

uste

d fo

r in

divi

dual

s liv

ing

10

year

s or

lo

nger

at

th

eir

1986

ad

dres

s: 1

.04

(0.6

5, 1

.64)

B

ackg

roun

d a

nd lo

cal

All

caus

e m

orta

lity

Una

djus

ted:

1.3

7 (1

.06,

1.7

7)

Adj

uste

d: 1

.32

(0.

98, 1

.78)

A

djus

ted

for

indi

vidu

als

livin

g 10

ye

ars

or

long

er

at

thei

r 19

86

addr

ess:

1.3

1 (0

.95,

1.8

0)

Car

diop

ulm

onar

y B

ackg

roun

d: 1

.34

(0.6

8, 2

.64)

B

ackg

roun

d a

nd l

ocal

1.7

1 (1

.10,

2.

67)

Non

-car

diop

ulm

onar

y no

n-lu

ng

canc

er

Bac

kgro

und:

1.1

5 (0

.63,

2.1

0)

Bac

kgro

und

and

loc

al 1

.09

(0.7

1,

1.69

) Lu

ng c

ance

r B

ackg

roun

d a

nd lo

cal:

1.06

(0.

43,

2.63

).

report no. 4/11

144

GER

MA

NY

G

ehrin

g et

al

. (2

006)

(G

ehrin

g et

al,

2006

) 7

citie

s of

N

orth

R

hine

-W

estp

halia

, Ger

man

y

Per

iod

of f

ollo

w-u

p: f

rom

19

85 to

200

2-20

03.

Sub

ject

s= 4

,752

M

ean

TS

P=

62.

4 (2

8.6)

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

long

-ter

m

expo

sure

to

P

M10

, ca

lcul

ate

d fr

om

TS

P b

y u

sing

a 0

.71

conv

ersi

on f

acto

r, N

O2

and

tota

l, ca

rdio

pulm

onar

y (I

CD

9: 4

00-4

40 a

nd 4

60-

519)

and

non

-car

diop

ulm

onar

y no

n-lu

ng c

ance

r m

orta

lity,

in

a

coho

rt

of

appr

oxim

ate

ly

4,80

0 G

erm

an

mid

dle-

age

wo

men

. T

he

limite

d nu

mbe

r of

de

aths

fo

r lu

ng

canc

er

and

pulm

onar

y ca

uses

did

not

allo

w t

o ob

tain

sta

ble

effe

ct e

stim

ates

, an

d co

rres

pond

ing

RR

s w

ere

no

t sh

ow

n.

RR

s w

ere

est

imat

ed

usin

g C

ox

prop

ortio

nal

haza

rd

regr

essi

on

mod

els

afte

r ad

just

men

t fo

r so

cio-

eco

nom

ic

stat

us

and

smok

ing.

1-y

ear

aver

age

daily

con

cent

ratio

n of

P

M10

for

the

yea

r of

the

bas

elin

e e

xam

inat

ion,

an

d 5-

year

ave

rage

dai

ly c

once

ntra

tion

of P

M10

fo

r th

e ye

ar o

f th

e ba

selin

e ex

amin

atio

n a

nd t

he

prec

edin

g 4

year

s w

ere

con

side

red.

Dur

ing

18 y

ear

follo

w-u

p, 3

99 w

omen

die

d.

One

-yea

r av

erag

e ex

posu

re

to

PM

10

(com

pute

d by

T

SP

) w

as

asso

ciat

ed

to

card

iopu

lmon

ary

mor

talit

y,

but

not

to

all

caus

e an

d

non

-car

diop

ulm

onar

y no

n-lu

ng

canc

er

mor

talit

y.

The

pa

ttern

of

ris

k w

as

sim

ilar

for

5-ye

ar a

vera

ge e

xpos

ure

to P

M10

. Li

ving

with

in a

50-

met

er r

adiu

s of

a m

ajor

ro

ad a

nd N

O2

leve

ls s

how

ed s

imila

r ris

ks.

Mod

estly

str

ong

er a

ssoc

iatio

ns w

ere

fou

nd

for

wom

en

with

a

low

so

cio-

econ

om

ic

stat

us,

for

curr

ent

smok

ers

and

for

non-

smok

ers

with

ex

pos

ure

to

envi

ronm

enta

l to

bacc

o sm

oke

(dat

a no

t sho

wn)

.

Mor

talit

y R

R f

or a

n in

crem

ent

of

7 μg

/m3 o

f P

M10

(co

rres

pond

ing

to

10 μ

g/m

3 of T

SP

):

1-ye

ar a

vera

ge

All

caus

es:

1.0

8 (0

.94-

1.25

) C

ardi

opul

mon

ary:

1.

34

(1.0

6-1.

71)

Non

-car

diop

ulm

onar

y no

n-lu

ng

canc

er: 0

.92

(0.7

6-1.

10)

5-ye

ar a

vera

ge

All

caus

es:

1.1

3 (0

.99-

1.30

) C

ardi

opul

mon

ary:

1.

59

(1.2

3-2.

04)

Non

-car

diop

ulm

onar

y no

n-lu

ng

canc

er: 0

.91

(0.7

6-1.

08).

report no. 4/11

145

FRA

NC

E

Fill

eul e

t al

. (2

005)

(F

illeu

l et

al,

2005

) P

AA

RC

sur

vey

24

area

s of

7

Fre

nch

citie

s pe

riod

of e

xpos

ure

mea

sure

men

t: 19

74-1

976

Sub

ject

s= 1

4,28

4 ad

ults

T

SP

min

/ma

x: 4

5/24

3 B

S m

in/m

ax:

18/

152.

Thi

s st

udy

exam

ined

the

lon

g te

rm e

ffect

s of

T

SP

, B

S,

SO

2,

NO

2 an

d N

O (

daily

ass

esse

d in

19

74-1

976)

on

m

orta

lity

in

the

Pol

lutio

n A

tmos

pher

iqu

e et

A

ffect

ions

R

espi

rato

ires

Chr

oniq

ues

(PA

AR

C)

surv

ey,

cond

ucte

d i

n 24

ar

eas

of

7 F

renc

h ci

ties

on

14,2

84

adul

ts,

follo

wed

for

the

per

iod

1974

-200

1. R

Rs

wer

e es

timat

ed

by

Co

x pr

opor

tiona

l ha

zard

re

gres

sion

m

odel

s,

afte

r ad

just

men

t fo

r ag

e,

sex,

sm

okin

g, B

MI,

educ

atio

n, a

nd o

ccup

atio

nal

expo

sure

. M

orta

lity

for

all n

on-a

ccid

enta

l cau

ses

(IC

D9

<80

0),

card

iopu

lmon

ary

dise

ase

(IC

D9:

40

1-44

0 an

d 46

0-51

9) a

nd l

ung

can

cer

(IC

D9:

16

2)

wer

e co

nsid

ered

. T

he

anal

yses

w

ere

perf

orm

ed f

or a

ll 24

are

as a

nd i

n a

subg

roup

of

18

area

s w

ith

a ra

tio

of

NO

/ N

O2

<3

(w

ith

mon

itors

pot

entia

lly in

fluen

ced

by lo

cal t

raffi

c).

Afte

r ap

prox

imat

ely

25 y

ears

of

follo

w-u

p,

appr

oxim

ate

ly

2,39

6 de

aths

fr

om

non-

acci

dent

al

caus

es,

546

fr

om

card

iopu

lmon

ary

dise

ase

and

178

fro

m lu

ng

canc

er

occu

rred

. C

onsi

deri

ng

all

the

24

area

s, n

o as

soci

atio

n w

as f

ound

bet

we

en

TS

P,

BS

an

d th

e ot

her

cons

ider

ed

co-

pollu

tant

s,

and

m

orta

lity

for

all

non

-ac

cide

ntal

ca

uses

, ca

rdio

pulm

onar

y di

seas

e, o

r lu

ng c

ance

r. A

fter

exc

lusi

on o

f 6

area

s in

fluen

ced

by

loca

l tr

affic

, T

SP

sh

ow

ed

a si

gnifi

cant

as

soci

atio

n w

ith

all

non-

acci

dent

al c

ause

s an

d ca

rdio

pulm

onar

y di

seas

e m

orta

lity,

and

BS

incr

ease

d th

e ris

k of

no

n-ac

cid

enta

l ca

use

s m

orta

lity.

N

O2

sign

ifica

ntly

in

crea

sed

the

mor

talit

y fo

r al

l no

n-ac

cide

nta

l ca

uses

, ca

rdio

pulm

onar

y di

seas

e an

d lu

ng

canc

er.

Aut

hors

co

nclu

ded

tha

t ur

ban

air

pollu

tion

asse

sse

d in

the

197

0s w

as

asso

ciat

ed

with

inc

reas

ed

mor

talit

y ov

er 2

5 ye

ars.

Mor

talit

y R

R f

or a

n in

crem

ent

of

10 μ

g/m

3 of T

SP

: 24

are

as:

Non

-acc

iden

tal:

1.00

(0.

99, 1

.01)

C

ardi

opul

mon

ary:

1.

01

(0.9

9,

1.03

) Lu

ng c

ance

r: 0

.97

(0.9

4, 1

.01)

18

are

as n

ot i

nflu

ence

d b

y lo

cal

traf

fic:

Non

, acc

iden

tal:

1.05

(1.

02, 1

.08)

C

ardi

opul

mon

ary:

1.

06

(1.0

1,

1.12

) Lu

ng c

ance

r: 1

.00

(0.9

2, 1

.10)

M

orta

lity

RR

for

an

incr

emen

t of

10

μg/

m3 o

f BS

: 24

are

as:

Non

-acc

iden

tal:

0.99

(0.

98, 1

.01)

C

ardi

opul

mon

ary:

1.

00

(0.9

7,

1.02

) Lu

ng c

ance

r: 0

.97

(0.9

3, 1

.01)

18

are

as n

ot i

nflu

ence

d b

y lo

cal

traf

fic:

Non

-acc

iden

tal:

1.07

(1.

03, 1

.10)

C

ardi

opul

mon

ary:

1.05

(0

.98,

1.

12)

Lung

can

cer:

1.0

3 (0

.92,

1.1

5).

report no. 4/11

146

TAB

LE V

I - E

CO

LOG

IC S

TUD

IES

ON

LO

NG

TER

M P

AR

TIC

ULA

TE M

ATT

ER E

XPO

SUR

E A

ND

MO

RTA

LITY

. Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

etho

ds, c

o-p

ollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

. PM

Inde

x, R

R (9

5% C

I)

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Mah

esw

aran

et

al

. (2

005b

) (M

ahes

war

an

et

al, 2

005b

) S

heffi

eld,

UK

, 19

94-1

998

Pop

ulat

ion:

19

9,68

2 su

bjec

ts a

ged ≥

45 y

ears

. P

M10

, med

ian:

18.

8.

To

exam

ine

the

rela

tion

betw

een

area

s w

ith

diffe

rent

air

pollu

tion

leve

ls a

nd c

oron

ary

hear

t di

seas

e (I

CD

9:

410-

414)

m

orta

lity

(and

ho

spita

lizat

ion

), 5

yea

r av

era

ge o

f P

M1

0, N

Ox

and

CO

leve

ls w

ere

inte

rpol

ated

to

1030

cen

sus

enum

erat

ion

dis

tric

ts,

and

lin

ked

to r

esid

ence

of

each

sub

ject

. P

oiss

on r

egre

ssio

n m

odel

s w

ere

us

ed a

fter

adj

ustm

ent

for

age

, se

x, d

epriv

atio

n an

d sm

okin

g pr

eval

ence

. T

o ad

just

for

sm

okin

g pr

eval

ence

, su

rvey

dat

a fr

om a

ran

dom

sam

ple

of a

dults

car

ried

out

in 2

00

0 w

as u

sed.

War

d le

vel

smok

ing

pre

vale

nce

wa

s at

trib

uted

to

all

dist

ricts

with

in e

ach

of t

he 2

9 w

ards

in S

hef

field

. A

naly

ses

wer

e re

run,

sub

stitu

ting

unsm

oot

hed

pollu

tion

vari

able

s w

ith

the

1km

ra

dius

sm

ooth

ed v

aria

bles

.

Dur

ing

the

pe

riod

199

4-19

98,

6,8

57 d

eath

s fo

r co

rona

ry h

eart

dis

ease

occ

urre

d. P

M10

w

as

sign

ifica

ntly

as

soci

ate

d w

ith

mor

talit

y fo

r co

rona

ry h

eart

dis

ease

in

the

age-

and-

sex-

adju

sted

m

odel

on

ly.

Afte

r fu

rthe

r al

low

ance

fo

r ot

her

cova

riate

s,

no

asso

ciat

ion

was

sho

wn.

A s

imila

r pa

ttern

of

risk

w

as

foun

d fo

r C

O.

NO

x in

crea

sed

mor

talit

y fo

r co

rona

ry h

eart

h di

seas

e ev

en

afte

r fu

rthe

r al

low

ance

fo

r sm

okin

g an

d de

priv

atio

n.

RR

for

the

hig

hest

vs

the

low

est

qu

intil

e of

e

xpos

ure

of

PM

10.

Mor

talit

y fo

r co

rona

ry

hear

t di

seas

e:

Adj

uste

d fo

r se

x an

d ag

e:

1.30

(1.

19, 1

.43)

F

urth

er a

djus

ted

for

smok

ing

and

depr

ivat

ion

(not

sm

ooth

ed):

1.

08 (

0.96

, 1.2

0)

Fur

ther

adj

uste

d fo

r sm

okin

g an

d de

priv

atio

n

(1km

ra

dius

sm

ooth

ed):

1.

07 (

0.96

, 1.2

1).

Mah

esw

aran

et

al

. (2

005a

) (M

ahes

war

an

et

al, 2

005a

) S

heffi

eld,

UK

, S

ame

stud

y de

scrib

ed

abov

e.

Thi

s st

udy

use

d th

e sa

me

dat

a an

d m

etho

ds

desc

ribed

ab

ove

to

exa

min

e th

e as

soci

atio

n be

twee

n P

M10

, N

Ox

and

CO

, an

d st

roke

(IC

D9:

43

0-43

8) m

orta

lity

(and

hos

pita

lizat

ion)

.

Dur

ing

the

pe

riod

199

4-19

98,

2,9

79 d

eath

s fo

r st

roke

occ

urre

d. P

M10

wa

s si

gnifi

can

tly

asso

ciat

ed w

ith s

trok

e m

orta

lity

also

aft

er

furt

her

allo

wan

ce

for

othe

r co

varia

tes,

in

clud

ing

smok

ing

prev

alen

ce

and

de

priv

atio

n.

Sim

ilar

patte

rns

of

risk

wer

e fo

und

for

NO

x an

d C

O.

RR

for

the

hig

hest

vs

the

low

est

qu

intil

e of

e

xpos

ure

of

PM

10.

Str

oke

mor

talit

y:

Adj

uste

d fo

r se

x an

d a

ge:

1.

39 (

1.23

, 1.5

8)

Fur

ther

adj

uste

d fo

r sm

okin

g an

d de

priv

atio

n (n

ot s

moo

thed

):

1.33

(1.

14, 1

.56)

F

urth

er a

djus

ted

for

smok

ing

and

depr

ivat

ion

(1

km

radi

us

smoo

thed

):

1.24

(1.

05, 1

.47)

.

report no. 4/11

147

IREL

AN

D

C

lanc

y et

al

. (2

002)

(C

lanc

y et

al,

2002

) D

ublin

, Ir

ela

nd,

1984

-19

96

Inte

rven

tion

stud

y S

ubje

cts:

4,4

92;

B

S

exp

osu

re,

mea

n an

nual

co

ncen

trat

ion

rang

ed

betw

een

10

an

d

120

befo

re t

he b

an,

and

betw

een

10

and

40

ther

eafte

r.

Thi

s st

udy

com

pare

d st

and

ardi

sed

non-

trau

ma

(IC

D9

<80

0),

resp

irato

ry

(IC

D9:

48

0-49

6 an

d 50

7),

and

card

iova

scul

ar (

ICD

9: 3

90-4

48)

deat

h ra

tes

72 m

onth

s be

fore

and

afte

r th

e ba

n of

coa

l sa

les

in D

ublin

(A

ug 1

990)

. T

he e

ffect

of

the

ban

on

age-

stan

dard

ised

de

ath

rate

s w

as

estim

ated

w

ith

an

inte

rrup

ted

time-

serie

s an

alys

is,

adju

stin

g fo

r w

eath

er,

resp

irato

ry

epid

emic

s, a

nd

deat

h ra

tes

in th

e re

st o

f Ire

land

.

Ave

rage

B

S

conc

entr

atio

ns

in

Dub

lin

decl

ined

by

35.

6 µ

g/m

3 (70

%)

afte

r th

e ba

n on

coa

l sa

les.

Adj

uste

d no

n-tr

aum

a de

ath

rate

s de

crea

sed

by 5

·7%

(95

% C

I: 4,

7),

re

spira

tory

dea

ths

by 1

5·5

% (

95%

CI:

12,

19),

an

d ca

rdio

vasc

ular

d

eath

s by

1

0·3%

(9

5%

CI:

8,

13).

R

espi

rato

ry

and

card

iova

scul

ar s

tand

ardi

sed

deat

h ra

tes

fell

coin

cide

nt w

ith th

e ba

n on

coa

l sal

es.

No

RR

sho

wn.

report no. 4/11

148

TAB

LE V

II - L

ON

G T

ERM

PA

RTI

CU

LATE

MA

TTER

EXP

OSU

RE

AN

D C

AR

DIO

VASC

ULA

R M

OR

BID

ITY.

Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

etho

ds, c

o-p

ollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

. PM

Inde

x, R

R (9

5% C

I)

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Mah

esw

aran

et

al

. (2

005b

) (M

ahes

war

an

et

al, 2

005b

) S

heffi

eld,

UK

, 19

94-1

998.

P

opul

atio

n:

199,

682

subj

ects

age

d ≥4

5 ye

ars.

P

M10

, med

ian:

18.

8.

To

exam

ine

the

rela

tion

betw

een

area

s w

ith

diffe

rent

air

pollu

tion

leve

ls a

nd c

oron

ary

hear

t di

seas

e (I

CD

9:

410-

414)

ho

spita

lizat

ion

(a

nd

mor

talit

y),

5 ye

ar a

vera

ge o

f P

M10

, N

Ox

and

CO

le

vels

w

ere

in

terp

olat

ed

to

1030

ce

nsus

en

umer

atio

n d

istr

icts

, an

d li

nke

d to

res

iden

ce o

f ea

ch s

ubje

ct.

Poi

sson

reg

ress

ion

mod

els

wer

e

used

aft

er a

djus

tmen

t fo

r a

ge,

sex,

dep

rivat

ion

and

smok

ing

prev

alen

ce.

To

adju

st f

or s

mok

ing

prev

alen

ce,

surv

ey d

ata

from

a r

ando

m s

ampl

e of

adu

lts c

arrie

d ou

t in

20

00

was

use

d. W

ard

leve

l sm

okin

g p

reva

lenc

e w

as

attr

ibut

ed t

o al

l di

stric

ts w

ithin

eac

h of

the

29

war

ds in

Sh

effie

ld.

Ana

lyse

s w

ere

reru

n, s

ubst

itutin

g un

smo

othe

d po

llutio

n va

riab

les

with

th

e 1k

m

radi

us

smoo

thed

var

iabl

es.

Dur

ing

the

perio

d 19

94-1

998,

11

,407

ad

mis

sion

s fo

r co

rona

ry

hear

t di

seas

e oc

curr

ed.

PM

10

wa

s as

soci

ated

w

ith

adm

issi

on f

or c

oron

ary

hear

t di

seas

e in

th

e ag

e-an

d-se

x-a

djus

ted

mod

el

only

. A

fter

fu

rthe

r al

low

anc

e fo

r ot

her

cova

riate

s,

no

asso

ciat

ion

was

sho

wn.

A s

imila

r pa

ttern

of

risk

was

foun

d fo

r C

O a

nd N

Ox.

RR

for

the

hig

hest

vs

the

low

est

qu

intil

e of

e

xpos

ure

of

PM

10.

Adm

issi

on

for

coro

nary

he

art

dise

ase:

A

djus

ted

for

sex

and

age:

1.

36 (

1.23

, 1.5

0)

Fur

ther

adj

uste

d fo

r sm

okin

g an

d de

priv

atio

n (n

ot s

moo

thed

):

1.01

(0.

90, 1

.14)

F

urth

er a

djus

ted

for

smok

ing

and

depr

ivat

ion

(1

km

radi

us

smoo

thed

):

1.07

(0.

95, 1

.20)

.

Mah

esw

aran

et

al

. (2

005a

) (M

ahes

war

an

et

al, 2

005a

) S

heffi

eld,

UK

, S

ame

stud

y de

scrib

ed

abov

e.

Thi

s st

udy

use

d th

e sa

me

dat

a an

d m

etho

ds

desc

ribed

ab

ove

to

exa

min

e th

e as

soci

atio

n be

twee

n P

M10

, N

Ox

and

CO

, an

d st

roke

(IC

D9:

43

0-43

8) h

ospi

taliz

atio

n (a

nd m

orta

lity)

.

Dur

ing

the

perio

d 19

94-1

998,

5,

122

adm

issi

ons

for

stro

ke o

ccur

red.

PM

10 w

as

sign

ifica

ntly

ass

ocia

ted

with

hos

pita

lizat

ion

for

stro

ke

in

the

age-

and-

sex-

adju

sted

m

odel

. A

fter

furt

her

allo

wan

ce

for

othe

r co

varia

tes,

a

bord

erlin

e si

gnifi

cant

as

soci

atio

n w

as s

how

n. S

imila

r pa

ttern

s of

ris

k w

ere

foun

d fo

r N

Ox

and

CO

.

RR

for

the

hig

hest

vs

the

low

est

qu

intil

e of

e

xpos

ure

of

PM

10.

Adm

issi

on fo

r st

roke

: A

djus

ted

for

sex

and

age

:

1.40

(1.

26, 1

.55)

F

urth

er a

djus

ted

for

smok

ing

and

depr

ivat

ion

(not

sm

ooth

ed):

1.

13 (

0.99

, 1.2

9)

Fur

ther

adj

uste

d fo

r sm

okin

g an

d de

priv

atio

n

(1km

ra

dius

sm

ooth

ed):

1.

15 (

1.01

, 1.3

1).

report no. 4/11

149

Sol

omon

et

al

. (2

003)

(S

olom

on e

t al,

2003

) 11

el

ecto

ral

war

ds

of

Eng

land

and

Wal

es, U

K.

1,16

6 w

omen

M

ean

BS

le

vel,

rang

e

acro

ss w

ards

: 19

66-1

969:

40/

180

1978

-198

1: 1

4/79

19

94-1

997:

4/1

4.

To

exp

lore

th

e lo

ng-t

erm

influ

ence

of

part

icul

ate

air

pollu

tion

on c

ardi

o-re

spirr

ator

y m

orbi

dity

in

the

UK

, a

cros

s-se

ctio

nal

post

al

surv

ey

was

co

nduc

ted

in 1

1 el

ecto

ral

war

ds o

f U

K.

War

ds

wer

e cl

assi

fied

in h

igh

(BS

>12

0 µ

g/m

3 in

196

6-19

69)

and

low

(B

S<

50

µg/

m3

in

1966

-196

9)

pollu

tion

cate

gor

ies.

W

omen

fro

m t

he t

wo

cate

gorie

s w

ere

com

pare

d in

te

rms

of

self-

repo

rted

hi

stor

y of

is

chae

mic

he

art

dise

ase

(and

as

thm

a an

d pr

oduc

tive

coug

h).

No

exc

ess

risk

of i

scha

emic

hea

rt d

isea

se

wa

s fo

und

in t

he a

reas

with

hig

her

leve

ls o

f B

S.

RR

for

wom

en

livin

g in

the

are

as

with

hig

her

BS

leve

ls:

1.0

(0.7

, 1.4

).

SWED

EN

R

osen

lund

et

al

. (2

006)

(R

osen

lund

et

al, 2

006)

S

tock

olm

, S

wed

en,

1992

-19

94.

Cas

e-co

ntro

l stu

dy

Sub

ject

s: 2

72 c

ases

with

fa

tal

myo

card

ial

infa

rctio

n

and

1,87

0 ho

spita

l co

ntro

ls.

30

year

re

side

ntia

l P

M10

ex

posu

re,

med

ian:

2.6

for

ca

ses

(incl

udin

g no

n-fa

tal

case

s)

and

2.4

for

cont

rols

.

Thi

s ca

se-c

ontr

ol

stud

y ex

amin

ed

the

asso

ciat

ion

bet

we

en 3

0 ye

ar a

vera

ge e

xpos

ure

to P

M10

, an

d ot

her

co-p

ollu

tant

s, i

nclu

din

g S

O2,

N

O2

and

CO

, an

d fir

st e

piso

de o

f no

n-fa

tal (

and

fata

l) m

yoca

rdia

l in

farc

tion

(M

I).

The

an

nual

m

ean

leve

l of

PM

10 w

as

asse

ssed

onl

y fo

r th

e ye

ar 2

000,

thu

s as

sum

ing

co

nsta

nt le

vels

dur

ing

the

stud

y pe

riod.

The

air

pollu

tion

data

for

eac

h ye

ar w

as l

inke

d to

the

his

tory

of

resi

denc

e of

ea

ch s

ubje

ct f

or t

he c

orre

spon

ding

yea

r fr

om

1960

to

stud

y in

clus

ion.

OR

s w

ere

deriv

ed b

y m

ultip

le

logi

stic

re

gres

sion

m

odel

s af

ter

adju

stm

ent

for

age,

se

x,

hosp

ital

catc

hmen

t ar

ea,

smok

ing,

phy

sica

l a

ctiv

ity,

diab

etes

and

so

cioe

cono

mic

sta

tus.

Est

imat

es f

or P

M2.

5 w

ere

no

t sh

own,

gi

ven

the

high

co

rrel

atio

n in

th

is

sam

ple

betw

een

PM

2.5

and

PM

10 (

r=0.

998

).

PM

10 w

as n

ot a

ssoc

iate

d w

ith n

onfa

tal

MI.

Sim

ilar

patt

erns

of

risk

wer

e fo

und

for

NO

2,

CO

, and

SO

2.

RR

for

an

incr

emen

t of

5 μ

g/m

3

(95th

–

5th

perc

entil

e)

of

PM

10.

Hos

pita

l ad

mis

sion

fo

r no

n-fa

tal

MI:

0.

92 (

0.71

, 1.1

9).

report no. 4/11

150

GER

MA

NY

H

offm

ann

et

al.

(200

6)

(Hof

fman

n et

al,

2006

) T

wo

citie

s o

f G

erm

any

(Ess

en

and

M

ulhe

im),

20

00-2

003.

C

ohor

t stu

dy

Sub

ject

s: 3

,39

9 M

ean

(SD

) P

M2.

5:

23.3

(1

.4)

.

Thi

s st

udy

exam

ined

the

rel

atio

nshi

p be

twee

n th

e lo

ng-t

erm

res

iden

tial

exp

osur

e to

tra

ffic

and

self-

repo

rted

his

tory

of

coro

nary

hea

rt d

isea

se,

usin

g ba

selin

e da

ta

from

th

e G

erm

an

Hei

nz

Nix

dorf

R

EC

ALL

st

udy,

a

popu

latio

n-ba

sed

coho

rt

stud

y.

Long

-ter

m

pers

onal

tr

affic

an

d P

M2.

5 e

xpos

ures

w

ere

asse

ssed

fo

r ea

ch

resi

dent

. P

M2.

5 w

as a

sses

sed

for

the

year

200

2.

OR

s w

ere

der

ived

by

m

ultiv

aria

ble

logi

stic

re

gres

sion

m

odel

s.

For

P

M2.

5 fo

ur

diffe

rent

m

odel

s w

ere

cons

ider

ed:

mod

el 1

: ad

just

ed f

or

traf

fic e

xpos

ure

; m

odel

2:

furt

her

adju

sted

for

ag

e an

d se

x;

mod

el

3:

furt

her

adju

sted

fo

r ed

ucat

ion,

di

abet

es,

BM

I,

wai

st-t

o-hi

p ra

tio,

smok

ing,

e

nviro

nmen

tal

toba

cco

smok

e,

phys

ical

ac

tivity

, ci

ty

and

area

of

re

side

nce;

m

odel

4:

furt

her

adj

uste

d fo

r hy

pert

ensi

on

and

lipid

s.

Ove

rall,

242

sub

ject

s re

port

ed a

his

tory

of

coro

nary

hea

rt d

isea

se.

No

asso

ciat

ion

was

fo

und

with

PM

2.5

expo

sure

, bu

t th

ere

was

an

exce

ss r

isk

in m

en o

nly

for

resi

dent

s liv

ing

near

maj

or r

oads

.

OR

fo

r P

M2.

5 (in

crem

ent

appa

rent

ly 1

μg/

m3 ):

M

odel

1: 0

.92

(0.3

6, 2

.39)

M

odel

2: 0

.83

(0.3

1, 2

.27)

M

odel

3: 0

.56

(0.1

6, 2

.01)

M

odel

4: 0

.55

(0.1

4, 2

.11)

.

report no. 4/11

151

TAB

LE V

III -

LON

G T

ERM

PA

RTI

CU

LATE

MA

TTER

EXP

OSU

RE

AN

D R

ESPI

RA

TOR

Y M

OR

BID

ITY

OR

SYM

PTO

MS

(Der

ived

from

EPA

TA

BLE

8B

-8).

Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

etho

ds, c

o-p

ollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

. PM

Inde

x, R

R (9

5% C

I)

ECR

HS

I stu

dy

S

unye

r et

al

. (2

006)

(S

unye

r et

al,

2006

) 21

cen

tres

of 1

0 co

untr

ies

Fol

low

-up

perio

d:

2000

-20

02.

Pop

ulat

ion:

6,8

24

PM

2.5

mea

n 1

9.12

S

mea

n 11

67.0

7

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

the

prev

alen

ce a

nd n

ew

on

set

of s

ympt

om

s of

ch

roni

c br

onch

itis

and

urb

an

leve

ls o

f P

M2.

5, S

, N

O2,

in

6,8

24 s

ubje

cts

enro

lled

durin

g 19

91–9

3 in

21

ce

ntre

s of

10

E

urop

ean

coun

trie

s.

Sub

ject

s w

ere

follo

wed

fr

om

2000

to

20

02.

PM

2.5

and

S w

ere

ass

esse

d at

cen

tre

leve

l w

ith

the

sam

e ce

ntra

l m

onito

ring

site

eq

uipm

ent,

whe

reas

NO

2 w

as

mea

sure

d du

ring

a 14

day

pe

riod

for

1,63

4 in

divi

dual

s of

16

ce

ntre

s at

ho

me

(out

door

and

ind

oor)

. T

wo

defin

itio

ns f

or

sym

ptom

s of

ch

roni

c br

onch

itis

wer

e

cons

ider

ed:

1)

prod

uctiv

e ch

roni

c co

ugh

for

chro

nic

coug

h a

nd c

hron

ic p

hleg

m (

mor

e th

an

thre

e m

onth

s ea

ch y

ear,

an

d 2)

chr

onic

phl

egm

al

one.

R

esu

lts

from

th

e la

tter

defin

ition

w

ere

sho

wn.

H

iera

rchi

cal

mo

dels

w

ere

us

ed.

Con

foun

ding

va

riabl

es

(incl

udin

g sm

okin

g,

educ

atio

n,

occu

patio

nal

grou

ps,

occu

patio

nal

expo

sure

s,

resp

irato

ry

infe

ctio

ns

durin

g ch

ildho

od,

rhin

itis,

and

ast

hm

a) w

ere

reta

ined

at

indi

vidu

al l

eve

l if

p <

0.1

0 or

the

coe

ffici

ent

of

the

air

pollu

tion

varia

ble

was

mod

ified

by

10%

or

m

ore.

F

or

PM

2.5,

th

e as

soci

atio

n w

as

mea

sure

d w

ith

inte

rval

o

dds

ratio

(t

hat

is,

cove

ring

80%

of t

he O

Rs)

.

Tra

ffic

inte

nsity

as

w

ell

as

hom

e ou

tdoo

r N

O2

wer

e as

soci

ated

with

(pr

eval

ence

and

ne

w o

nse

t of

= c

hron

ic p

hleg

m,

in w

omen

on

ly.

PM

2.5

and

S c

onte

nt a

t ce

ntre

leve

l did

no

t sh

ow

any

ass

ocia

tion

with

pre

vale

nce

or

new

ons

et o

f ch

roni

c ph

leg

m.

Sim

ilar

resu

lts

wer

e

obta

ine

d w

ith

chro

nic

prod

uctiv

e co

ugh.

Inte

rval

OR

(95

% C

I))

for

PM

2.5

in

µg/

m3

Mal

es: 0

.97

(0.7

0, 1

.35)

F

emal

es: 0

.99

(0.8

5, 1

.17)

.

report no. 4/11

152

CES

AR

stu

dy

Le

onar

di

et

al.

(200

0)

(Leo

nard

i et a

l, 20

00)

17

citie

s of

C

entr

al

Eur

ope

Y

early

av

erag

e co

ncen

trat

ion

(Nov

. 19

95

- O

ct.

1996

) ac

ross

th

e

17

stud

y ar

eas

varie

d

from

41

to 9

6 fo

r P

M10

, fr

om 2

9 to

67

for

PM

2.5,

an

d fr

om

12

to

38

for

PM

10-2

.5.

Cro

ss-s

ectio

nal

st

udy

colle

cted

bl

ood

an

d se

rum

sam

ples

fro

m 1

0-61

sch

ool c

hild

ren

age

d 9

to 1

1 in

ea

ch c

omm

unity

11

Apr

il to

10

May

19

96.

Blo

od a

nd s

erum

sam

ples

exa

min

ed f

or

para

met

ers

in

rela

tion

to

PM

. F

inal

a

naly

sis

grou

p of

36

6 ex

amin

ed

for

perip

hera

l ly

mph

ocyt

e ty

pe

and

tota

l im

mun

oglo

bulin

cl

asse

s. A

sso

ciat

ion

betw

een

PM

and

eac

h lo

g

tran

sfor

med

bi

omar

ker

stud

ied

by

linea

r re

gres

sion

in

two-

stag

e m

odel

with

adj

ust

men

t fo

r co

nfou

ndin

g fa

ctor

s (a

ge,

gend

er,

num

ber

of

smok

ers

in

hous

e,

labo

rato

ry,

and

rece

nt

resp

irato

ry i

llnes

s).

Thi

s su

rvey

was

con

duc

ted

with

in t

he f

ram

e w

ork

of t

he

Cen

tral

Eur

opea

n st

udy

of

Air

Qua

lity

and

Res

pira

tory

H

ealth

(C

EA

SA

R)

stu

dy.

Num

ber

of l

ymph

ocyt

es (

B,

CD

4+

, C

D8

d,

and

NK

) in

crea

sed

with

in

crea

sin

g co

ncen

trat

ion

of

P

M

adju

sted

fo

r co

nfou

nder

s.

The

ad

just

ed

regr

essi

on

slop

es

are

larg

est

and

stat

istic

ally

si

gnifi

cant

for

PM

2.5

as c

om

pare

d to

PM

10,

but

smal

l an

d no

n st

atis

tical

ly s

igni

fican

t fo

r P

M10

-2.5.

Pos

itive

re

latio

nshi

p fo

und

betw

een

conc

entr

atio

n of

Ig

G i

n se

rum

and

P

M2.

5 bu

t no

t fo

r P

M10

or

PM

10-2

.5.

Tw

o ot

her

m

odel

s pr

oduc

ed s

imila

r ou

tcom

es:

a m

ulti-

le

vel l

inea

r re

gres

sion

mod

el a

nd a

n or

dina

l lo

gist

ic r

egre

ssio

n m

odel

.

Adj

uste

d R

egre

ssio

n sl

ope

P

M2.

5

CD

4+

80%

(34

, 143

) p<

0.00

1

Tot

al Ig

G

24%

(2,

52)

p=

0.03

4.

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Sol

omon

et

al

. (2

003)

(S

olom

on e

t al,

2003

) 11

el

ecto

ral

war

ds

of

Eng

land

and

Wal

es, U

K.

1,16

6 w

omen

M

ean

BS

le

vel,

rang

e

acro

ss w

ards

: 19

66-1

969:

40/

180

1978

-198

1: 1

4/79

19

94-1

997:

4/1

4.

To

exp

lore

th

e lo

ng-t

erm

influ

ence

of

part

icul

ate

air

pollu

tion

on

ca

rdio

-res

pira

tory

m

orbi

dity

in

th

e U

K,

a cr

oss-

sect

iona

l po

stal

su

rvey

w

as

cond

ucte

d in

11

elec

tora

l war

ds o

f U

K o

n 1

,166

w

omen

. W

ard

s w

ere

clas

sifie

d in

hig

h (B

S>

120

µg/

m3 i

n 19

66-

1969

) an

d lo

w (

BS

<50

µg/

m3 i

n 19

66-1

969)

pol

lutio

n ca

tego

ries.

W

omen

fro

m t

he t

wo

cate

gorie

s w

ere

com

pare

d in

ter

ms

of s

elf-

repo

rted

his

tory

of

asth

ma

and

prod

uctiv

e co

ugh

(and

IHD

).

The

pre

vale

nce

of a

sthm

a w

as

low

er i

n th

e ar

eas

with

hig

her

leve

ls o

f B

S.

No

exc

ess

ris

k of

pro

duct

ive

coug

h w

as f

ound

in

the

area

s w

ith h

ighe

r le

vels

of B

S.

RR

for

wom

en

livin

g in

the

are

as

with

hig

her

BS

leve

ls:

Ast

hma:

0.7

(0.

5, 1

.0)

Pro

duct

ive

coug

h: 1

.0 (

0.7,

1.4

).

report no. 4/11

153

Whe

eler

and

Ben

-Shl

omo

(200

5)

(Whe

eler

an

d B

en-S

hlom

o, 2

005)

Li

nkag

e an

alys

is,

Eng

land

, 199

5-19

97.

Mea

n (S

D)

PM

10:

23.9

5 (3

.58)

; ra

nge:

17

.87-

41.3

7.

Thi

s st

udy

exam

ined

th

e re

latio

n be

twee

n so

cioe

cono

mic

sta

tus

and

loca

l ai

r qu

ality

, an

d

com

bine

d ef

fect

s on

res

pira

tory

hea

lth,

Dat

a on

pe

ople

ta

king

pa

rt

in

the

Hea

lth

Sur

veys

fo

r E

ngla

nd

durin

g 19

95-1

997

wer

e at

trib

uted

with

a s

mal

l are

a in

dex

of a

ir po

llutio

n ba

sed

on a

nnua

l m

ean

conc

entr

atio

ns o

f P

M10

, be

nzen

e,

SO

2 an

d N

O2.

R

egre

ssio

n m

odel

s af

ter

adju

stm

ent

for

smok

ing

stat

us,

pass

ive

smok

ing,

B

MI,

rura

lity,

pr

evio

us

asth

ma

diag

nosi

s an

d in

hale

r us

e w

ere

used

to

m

easu

re a

ssoc

iatio

ns b

etw

een

soci

al c

lass

, ai

r qu

ality

, ag

e-,

sex-

an

d he

ight

-sta

ndar

dize

d F

EV

1, a

nd s

elf r

epor

ted

asth

ma.

Urb

an l

ower

soc

ial

clas

s ho

useh

olds

wer

e m

ore

likel

y to

be

loca

ted

in a

reas

of

poor

air

qual

ity,

but

the

asso

ciat

ion

in

rura

l ar

eas

was

, if

anyt

hing

rev

erse

d. L

ow s

ocia

l cl

ass

and

poor

ai

r qu

ality

w

ere

inde

pend

ently

as

soci

ated

w

ith

decr

ease

d lu

ng

func

tion

(FE

V1)

, bu

t no

t as

thm

a pr

eval

ence

, af

ter

adju

stm

ent

for

a nu

mbe

r of

po

tent

ial

conf

ound

ers.

Soc

ial

clas

s ef

fect

s w

ere

not

atte

nuat

ed

by

adju

stm

ent

for

air

qual

ity.

Aut

hors

co

nclu

ded

that

th

e as

soci

atio

n be

twee

n F

EV

1 an

d lo

cal

air

qual

ity w

as o

f si

mila

r m

agni

tude

to

that

with

soc

ial

clas

s,

and

the

adve

rse

effe

cts

of

air

pollu

tion

seem

ed t

o be

gre

ater

in m

en in

low

er s

ocia

l cl

asse

s.

No

estim

ates

fo

r P

M

wer

e pr

ovid

ed.

Pie

rse

et

al.

(200

6)

(Pie

rse

et a

l, 20

06)

Coh

ort

of 4

,400

chi

ldre

n fr

om L

eice

ster

, UK

. 19

98-2

001.

A

nnua

l m

ean

conc

entr

atio

n of

P

M10

w

as

1.47

in

19

98

and

1.33

in 2

001.

Thi

s st

udy

exam

ined

he

effe

ct o

f pr

imar

y P

M10

(p

artic

les

dire

ctly

em

itted

fro

m lo

cal s

ourc

es)

on

prev

alen

ce

and

inci

denc

e of

re

spira

tory

sy

mpt

oms

in a

ran

dom

sam

ple

coho

rt o

f 4,

400

Leic

este

rshi

re

child

ren

aged

1–

5 ye

ars

surv

eyed

in

1998

and

aga

in i

n 20

01.

Ann

ual

expo

sure

to

prim

ary

PM

10 w

as c

alcu

late

d fo

r th

e ho

me

addr

ess

usin

g th

e A

IVIR

O

disp

ersi

on

mod

el a

nd O

Rs

wer

e ca

lcul

ated

for

eac

h µ

g/m

3 in

crea

se,

afte

r ad

just

men

t fo

r ag

e, s

ex,

fam

ily

hist

ory

of

asth

ma,

co

al

heat

ing

in

the

hom

e,

hous

ehol

d m

embe

r’s

smok

ing

stat

us,

and

mat

erna

l and

pat

erna

l edu

catio

n.

Exp

osur

e to

prim

ary

PM

10 w

as a

ssoc

iate

d w

ith t

he p

reva

lenc

e of

cou

gh w

ithou

t a

cold

in

bo

th

1998

an

d 20

01,

and

with

th

e pr

eval

ence

of

nigh

t tim

e co

ugh

and

curr

ent

whe

eze

in

2001

, on

ly.

An

asso

ciat

ion

betw

een

prim

ary

PM

10

and

inci

denc

e of

co

ugh

with

out

a co

ld a

nd w

heez

e w

as a

lso

foun

d.

Adj

uste

d O

R

(95%

C

I)

for

an

in

crem

ent o

f 1 µ

g/m

3 P

reva

lenc

e:

Cou

gh w

ithou

t a c

old

19

98: 1

.21

(1.0

7, 1

.38)

20

01: 1

.56

(1.3

2, 1

.84)

N

ight

tim

e co

ugh

19

98: 1

.06

(0.9

4, 1

.19)

20

01: 1

.25

(1.0

6, 1

.47)

C

urre

nt w

heez

e

1998

: 0.9

9 (0

.88,

1.1

2)

2001

: 1.2

8 (1

.04,

1.5

8)

Inci

denc

e (n

ew o

nset

sym

ptom

s,

not

pres

ent

in 1

998

surv

ey a

nd

pres

ent

in t

he 2

001

surv

ey v

ersu

s no

sym

ptom

s in

bot

h su

rvey

s)

Cou

gh w

ithou

t a c

old

1.

62 (

1.31

, 2.0

0)

Nig

ht ti

me

coug

h

1.19

(0.

96, 1

.47)

C

urre

nt w

heez

e

1.42

(1.

02, 1

.97)

.

report no. 4/11

154

Kul

karn

i et

al

. (2

006)

(K

ulka

rni e

t al,

2006

) Le

ices

ter,

UK

. N

ov 2

002

to D

ec 2

003.

A

nnua

l m

ean

leve

l of

P

M10

w

as

1.21

(r

ange

: 0.

10-2

.71)

in

he

alth

y ch

ildre

n an

d 1.

81 (

rang

e:

0.17

-2.1

3)

in

asth

mat

ic

child

ren.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

carb

on

cont

ent

ai

rway

m

acro

phag

es,

as

a m

arke

r of

in

divi

dual

e

xpo

sure

to

P

M

deriv

ed

from

fos

sil f

uel,

and

lung

fun

ctio

n in

9 a

sth

mat

ic

and

64

heal

thy

child

ren

from

Le

ices

ter,

U

K.

Air

way

m

acro

phag

es

we

re

obta

ined

fr

om

heal

thy

child

ren

thro

ugh

sput

um i

nduc

tion,

and

th

e ar

ea o

f ai

rway

mac

rop

hage

s oc

cupi

ed b

y ca

rbon

w

as

mea

sure

d.

Lung

fu

nctio

n w

as

mea

sure

d w

ith

the

use

of

spiro

met

ry.

The

ex

posu

re t

o P

M10

was

mo

del

ed a

t or

nea

r ea

ch

child

’s

hom

e

addr

ess.

Li

nea

r re

gres

sio

n w

as

used

to

eval

uate

ass

ocia

tions

bet

we

en c

arbo

n co

nten

t of

alv

eola

r m

acro

phag

es a

nd v

aria

bles

th

at m

ay a

ffect

ind

ivid

ual

expo

sure

. A

ge,

se

x,

race

, w

eig

ht,

heig

ht,

birt

h or

der,

nu

mbe

r of

si

blin

gs,

exe

rcis

e m

easu

res

and

cotin

ine

leve

ls

in

saliv

a w

ere

con

sid

ered

as

po

tent

ial

conf

ound

ing

varia

bles

.

An

incr

ease

in

PM

10 w

as a

ssoc

iate

d w

ith a

si

gnifi

cant

inc

reas

e in

the

ca

rbon

con

tent

of

airw

ay

mac

roph

ages

. C

arb

on c

onte

nt w

as

inve

rsel

y as

soci

ated

w

ith

FE

V1,

F

VC

an

d F

EF

25-7

5.

Incr

ease

d pr

imar

y P

M10

w

as

inve

rsel

y as

soci

ated

with

th

e pe

rcen

tage

of

the

pred

icte

d F

EV

1 (P

=

0.

04)

and

the

FE

F25

–75

(P

=

0.05

).

In

the

mul

tiple

re

gres

sion

ana

lysi

s, e

ven

afte

r ad

just

ing

for

the

carb

on c

onte

nt o

f ai

rwa

y m

acro

phag

es,

PM

10 w

as n

o l

onge

r si

gnifi

cant

ly a

ssoc

iate

d w

ith

lung

fu

nctio

n,

whe

reas

th

e ca

rbon

co

nten

t of

ai

rwa

y m

acro

phag

es

rem

aine

d in

vers

ely

asso

ciat

ed w

ith t

he

perc

enta

ge o

f th

e pr

edic

ted

valu

es

of

FE

V1,

F

VC

, a

nd

FE

F25

–75.

T

he

carb

on

cont

ent

of

airw

ay

mac

roph

ages

w

as

low

er

in

child

ren

with

as

thm

a th

an

in

heal

thy

child

ren.

A

uth

ors

conc

lude

d th

at

whi

le

ther

e w

as

a do

se-

depe

nden

t in

vers

e as

soci

atio

n be

twee

n th

e ca

rbon

con

ten

t of

airw

ay

mac

roph

ages

and

lu

ng

func

tion

in

ch

ildre

n,

ther

e w

as

no

evid

ence

th

at

redu

ced

lun

g fu

nctio

n its

elf

caus

ed a

n in

crea

se in

car

bon

cont

ent.

Exc

ess

carb

on

cont

ent

(µm

2 ) an

d lu

ng f

unct

ion

(%)

asso

ciat

ed

with

an

in

crem

ent

of

one

µg/

m3

of

PM

10.

carb

on

cont

ent

airw

ay

mac

roph

ages

: 0.

10 (

0.01

, 0.1

8)

FE

V1

-4.3

% (

-8.5

, -0.

2)

afte

r al

low

anc

e fo

r ca

rbon

co

nten

t: -2

.9%

(-6

.9, 1

.2)

FV

C

-1.2

% (

-5.6

, 3.2

) af

ter

allo

wa

nce

for

carb

on

cont

ent:

0.1%

(-4

.4, 4

.6)

FE

V1

-8.6

% (

-17.

3, 0

.1)

afte

r al

low

anc

e fo

r ca

rbon

co

nten

t: -5

.5%

(-1

4.2,

3.1

).

report no. 4/11

155

Bur

r et

al.

(200

4) (

Bur

r et

al

, 200

4)

Inte

rven

tion

stud

y,

Nor

th

Wal

es, U

K.

mea

n co

ncen

trat

ion

of

PM

10

Con

gest

ed s

tree

ts:

1996

-199

7: 3

5.2

1998

-199

9:27

.2

Unc

onge

sted

str

eets

: 19

96-1

997:

11.

6 19

98-1

999:

8.2

PM

2.5

C

onge

sted

str

eets

: 19

96-1

997:

21.

2 19

98-1

999:

16.2

U

ncon

gest

ed s

tree

ts:

1996

-199

7: 6

.7

1998

-199

9: 4

.9.

Thi

s st

udy

exam

ine

d w

heth

er

resi

dent

s of

co

nges

ted

stre

ets

had

a hi

gher

pre

vale

nce

of

resp

irato

ry

sym

ptom

s th

an

resi

dent

s of

un

cong

este

d

stre

ets,

an

d w

heth

er

thei

r re

spira

tory

he

alth

im

prov

es

follo

win

g a

redu

ctio

n in

ex

posu

re

to

traf

fic

rela

ted

air

pollu

tant

s,

due

to

the

con

stru

ctio

n of

a

“b

y-pa

ss”.

A r

espi

rato

ry s

urve

y w

as c

ondu

cted

at

base

line

and

ag

ain

a ye

ar

afte

r th

e by

-pas

s op

ened

on

16

5 an

d 28

3 su

bjec

ts

in

the

cong

este

d

and

unco

nges

ted

ar

eas,

re

spec

tivel

y.

Initi

al

conc

entr

atio

ns

of

PM

10

and

PM

2.5

wer

e su

bsta

ntia

lly h

ighe

r in

the

con

gest

ed

than

in

the

unco

nges

ted

stre

ets.

Whe

n th

e by

-pas

s op

ene

d,

the

volu

me

of

heav

y go

ods

traf

fic

fell

by

nea

rly

50%

. P

M10

de

crea

sed

by

23%

(8

.0

mg/

m3 )

in

the

cong

este

d st

reet

s an

d by

29%

(3.

4 m

g/m

3 ) in

th

e un

cong

este

d st

reet

s,

with

si

mila

r pr

opor

tiona

te

falls

in

P

M2

.5.

The

by

-pas

s sh

ow

ed a

ten

denc

y fo

r m

ost

sym

ptom

s to

im

prov

e in

bo

th

area

s.

The

im

prov

emen

t te

nded

to

be

gr

eate

r in

th

e un

cong

este

d ar

ea f

or c

hest

sym

ptom

s an

d fo

r pe

ak f

low

va

riabi

lity,

an

d in

the

con

ges

ted

stre

ets

for

rhin

itis

and

rhin

ocon

junc

tiviti

s T

he b

y-pa

ss

redu

ced

pollu

tant

le

vels

to

a

degr

ee

that

pr

obab

ly

alle

viat

es

rhin

itis

and

rhin

ocon

junc

tiviti

s bu

t h

as

little

ef

fect

on

lo

wer

res

pira

tory

sym

ptom

s.

No

estim

ates

fo

r P

M10

no

r fo

r P

M2.

5 w

ere

prov

ided

.

THE

NET

HER

LAN

DS

B

raue

r et

al

. (2

002)

; (B

raue

r et

al,

2002

) B

irth

coho

rt

of

3,93

4 ch

ildre

n.

PM

2.5

mea

n: 1

6.9

(ran

ge:

13.5

-25.

2).

Thi

s st

udy

exam

ined

the

rel

atio

nshi

p be

twee

n tr

affic

-rel

ated

ai

r po

llutio

n an

d

the

pred

evel

opm

ent

of a

sthm

atic

/alle

rgic

sym

ptom

s an

d re

spira

tory

inf

ectio

ns (

incl

udin

g w

heez

ing,

dr

y ni

ght-

time

coug

h, e

ar,

nose

, th

roat

(E

,N,T

) in

fect

ions

, sk

in r

ash,

and

phy

sici

an-d

iag

nose

d as

thm

a, b

ronc

hitis

, in

fluen

za,

and

ecze

ma

at 2

ye

ars

of a

ge)

in a

coh

ort

of a

ppro

xim

ate

ly 4

,000

bi

rths

. A

va

lidat

ed m

odel

wa

s us

ed t

o as

sign

ou

tdoo

r co

ncen

trat

ions

of

P

M2.

5,

NO

2 at

th

e ho

me

of

each

su

bjec

t o

f th

e co

hort

. T

he

asso

ciat

ion

bet

we

en P

M e

xpos

ure

and

vario

us

outc

omes

w

as

anal

yzed

by

m

ultip

le

logi

stic

re

gres

sion

af

ter

adju

stm

ent

for

vario

us

cova

riate

s,

incl

udin

g se

x,

smok

ing

an

d ed

ucat

ion

of p

aren

ts,

fam

ily h

isto

ry o

f al

lerg

ies,

an

d m

othe

r’s a

ge.

Adj

uste

d od

ds

ratio

s fo

r w

heez

ing,

ph

ysic

ian-

diag

nose

d as

thm

a,

E,N

,T

infe

ctio

ns,

and

flu/s

erio

us

cold

s in

dica

ted

posi

tive

asso

ciat

ions

w

ith

air

pollu

tant

s,

som

e of

whi

ch r

each

ed b

orde

rline

sta

tistic

al

sign

ifica

nce.

N

o as

soci

atio

ns

wer

e ob

serv

ed fo

r th

e ot

her

outc

omes

ana

lyze

d.

Adj

uste

d O

R (

95%

CI)

for

an

IQR

ch

ange

in

co

ncen

trat

ion

of

PM

(i.

e., 3

.2µ

g/m

3 ) W

heez

e: 1

.14

(0.9

8, 1

.34)

A

sthm

a: 1

.12

(0.8

4, 1

.50)

D

ry

coug

h at

ni

ght:

1.04

(0

.88,

1.

23)

Bro

nchi

tis: 1

.04

(0.8

5, 1

.26)

E

,N,T

infe

ctio

ns: 1

.20

(1.0

1, 1

.42)

F

lu/s

erio

us

cold

s:

1.12

(1

.00,

1.

27)

Itchy

ras

h: 1

.01

(0.8

8, 1

.16)

E

czem

a: 0

.95

(0.8

3, 1

.10)

.

report no. 4/11

156

Bra

uer

et

al.

(200

6);

(Bra

uer

et a

l, 20

06)

Birt

h co

hort

s on

3,

700

and

650

infa

nts

fro

m t

he

Net

herla

nds

and

Mun

ich

(Ger

man

y), r

espe

ctiv

ely.

P

erio

d of

re

crui

tmen

t: 19

97-1

998.

P

M2.

5 m

ean:

T

he N

ethe

rland

s: 1

6.9

Mun

ich,

Ger

man

y: 1

3.4.

Thi

s st

udy

anal

ysed

th

e as

soci

atio

n b

etw

een

P

M2.

5 el

emen

tal

carb

on,

and

NO

2, a

nd r

isk

of

otiti

s m

edia

in t

wo

birt

h co

hort

s of

app

roxi

mat

ely

3,70

0 an

d 65

0 in

fant

s fr

om t

he N

ethe

rland

s an

d

Ger

man

y, r

espe

ctiv

ely.

Air

pol

luta

nts

at h

ome

of

child

ren

wer

e m

easu

red

at 4

0 in

divi

dua

l si

tes

in

each

co

untr

y,

and

anal

yzed

in

re

latio

n to

di

agno

sed

hist

ory

of o

titis

med

ia (

diag

nose

d by

a

phys

icia

n)b

y pa

rent

s of

chi

ldre

n in

the

firs

t 2

year

s of

lif

e.

OR

s w

ere

deriv

ed

by

mul

tiple

lo

gist

ic r

egre

ssio

n m

odel

s af

ter

adju

stm

ent

for

pote

ntia

l co

nfou

ndin

g va

riabl

es,

incl

udin

g se

x,

pare

ntal

at

opy

, m

ater

nal

educ

atio

n

and

smok

ing,

en

viro

nmen

tal

toba

cco

smok

e an

d pr

esen

ce o

f pet

at h

ome,

and

sib

lings

.

Som

e si

gnifi

cant

di

rect

as

soci

atio

ns

we

re

obse

rved

bet

wee

n va

rious

mea

sure

s of

air

pollu

tion

and

in

cide

nce

of

otiti

s m

edia

. C

rude

an

d

adju

sted

O

Rs

wer

e sy

stem

atic

ally

ov

er

unity

fo

r al

l th

e co

nsid

ered

po

lluta

nts

and

in

bo

th

the

coho

rts.

Adj

uste

d O

R f

or a

n in

crea

se i

n 3

µg/

m3 o

f PM

2.5:

The

Net

herla

nds

At 1

yea

r of

age

: 1.1

3 (0

.98,

1.3

2)

At

2 ye

ars

of

age:

1.

13

(1.0

0,

1.27

) M

unic

h, G

erm

any

At 1

yea

r of

age

: 1.1

9 (0

.73,

1.9

2)

At

2 ye

ars

of

age:

1.

24

(0.8

4,

1.83

).

GER

MA

NY

H

einr

ich

et

al.

(199

9)

(Hei

nric

h et

al,

1999

) B

itter

feld

, Z

erbs

tand

H

etts

tedt

are

as

of fo

rmer

E

ast G

erm

any,

D

urin

g S

ept.

1992

to

July

19

93 T

SP

ran

ged

from

44

to 6

5;

PM

10

mea

sure

d O

ctob

er

1993

-

Mar

ch

1994

ra

nged

fro

m 3

to

40;

and

BS

ran

ged

fro

m 2

6 to

42.

P

M w

as m

easu

red

with

a

Har

vard

impa

ctor

.

Par

ents

of

247

0 sc

hool

chi

ldre

n (

5-14

yea

r)

com

plet

ed

resp

irato

ry

hea

lth

ques

tionn

aire

. C

hild

ren

exc

lude

d fr

om a

naly

sis

if ha

d liv

ed

< 2

ye

ars

in t

heir

curr

ent

hom

e, y

ield

ing

an a

naly

sis

grou

p of

2,

335

child

ren.

O

utco

mes

st

udie

d:

phys

icia

n d

iagn

osis

fo

r as

thm

a,

bron

chiti

s,

sym

ptom

, br

onch

ial

reac

tivity

, sk

in

pric

k te

st,

spec

ific

IgE

. M

ultip

le

logi

stic

re

gre

ssio

n an

alys

es e

xam

ined

reg

iona

l effe

cts.

Con

trol

ling

for

med

ical

, so

cio-

dem

ogra

phic

, an

d in

door

fac

tors

, ch

ildre

n in

mor

e po

llute

d ar

ea h

ad c

irca

50%

inc

rea

se f

or b

ronc

hitic

sy

mpt

oms

and

phys

icia

n-di

agno

sed

alle

rgie

s co

mpa

red

to c

ontr

ol a

rea

and

circ

a tw

ice

the

re

spira

tory

sy

mp

tom

s (w

heez

e,

shor

tnes

s of

bre

ath

and

coug

h).

Pul

mon

ary

func

tion

test

s su

gges

ted

slig

htly

inc

reas

ed

airw

ay

reac

tivity

to

co

ld

for

child

ren

in

po

llute

d ar

ea.

No

sing

le

pol

luta

nt

coul

d be

se

para

ted

out

as

bein

g

resp

onsi

ble

for

poor

re

spira

tory

he

alth

.

report no. 4/11

157

Hei

nric

h et

al

. (2

000)

(H

einr

ich

et a

l, 20

00)

Thr

ee a

reas

of

form

er E

. G

erm

any

Pol

lutio

n m

easu

res:

SO

2,

TS

P,

and

som

e lim

ited

P

M10

da

ta.

TS

P

decr

ease

d fr

om

65,

48,

and

44 t

o 43

, 39

, an

d 36

in

the

thre

e ar

eas.

P

M w

as m

easu

red

with

a

Har

vard

impa

ctor

.

Cro

ss-s

ectio

nal

st

udy

of

child

ren

(5-1

4 ye

ar).

S

urve

y co

nduc

ted

twic

e,

in

1992

-199

3 an

d 19

95-1

996;

2,

335

child

ren

surv

eyed

in

fir

st

roun

d, a

nd 2

,536

in

seco

nd

roun

d. O

nly

971

child

ren

app

eare

d in

bo

th

surv

eys.

T

he

freq

uenc

y of

br

onch

itis,

ot

itis

med

ia,

fre

quen

t co

lds,

fe

brile

in

fect

ions

st

udie

d.

Bec

ause

ch

ange

s m

easu

red

over

tim

e in

sa

me

area

s,

cova

riate

adj

ust

men

ts n

ot n

eces

sary

.

PM

and

SO

2 le

vels

bot

h d

ecre

ased

in

the

sam

e ar

eas;

so

resu

lts a

re c

onfo

unde

d.

The

pre

vale

nce

of a

ll re

spira

tory

sy

mpt

oms

decr

ease

d si

gnifi

cant

ly

in a

ll th

ree

area

s ov

er ti

me.

Hei

nric

h et

al

. (2

002)

(H

einr

ich

et a

l, 20

02)

Sur

veye

d ch

ildre

n ag

ed

5-14

in 1

992-

3, 1

995-

6,

1998

-9.

An

nual

T

SP

le

vels

ran

ged

from

25-

79.

Sm

all

part

icle

s (N

C0.

01-2

.5

per

103c

m-3

) re

mai

ned

rela

tivel

y co

nsta

nt.

A t

wo-

stag

e l

ogi

stic

reg

ress

ion

mod

el w

as

used

to

an

alyz

e

the

data

w

hich

ad

just

ed

for

age,

ge

nder

, ed

ucat

iona

l lev

el o

f pa

rent

s, a

nd in

door

fa

ctor

s. T

he m

odel

inc

lude

d fix

ed a

rea

effe

cts,

ra

ndom

de

viat

ions

, an

d er

rors

fr

om

the

adju

stm

ents

. P

aram

eter

s w

ere

estim

ated

usi

ng

GE

E m

etho

ds.

The

stu

dy f

ound

bro

nchi

tis a

nd f

requ

ency

of

cold

s w

ere

sig

nific

antly

rel

ated

to T

SP

. A

n in

crem

ent

of

50

µg/

m3

TS

P

wa

s as

soci

ated

w

ith

an

OR

fo

r br

onch

itis

of 3

.02

(1.7

2, 5

.29)

and

an

O

R

of

1.90

(1

.17,

3.

09)

fo

r fr

eque

ncy

of c

olds

.

Fry

e et

al.

(200

3) (

Fry

e et

al

, 200

3)

Sur

veye

d ch

ildre

n in

19

92-3

, 19

95-6

, 19

98-9

. A

nnua

l T

SP

le

vels

ra

nged

from

23-

79.

Thi

s st

udy

exam

ined

the

effe

cts

of i

mpr

oved

air

qual

ity

sinc

e 19

90

in

Eas

t G

erm

any

on

lung

fu

nctio

n in

ch

ildre

n. T

hree

con

secu

tive

cros

s-se

ctio

nal

surv

eys

of s

choo

lchi

ldre

n ag

ed 1

1–14

ye

ars

from

thr

ee c

omm

uniti

es i

n E

ast

Ge

rman

y w

ere

perf

orm

ed

durin

g 19

92-1

999.

Lu

ng

func

tion

test

s w

ere

ava

ilabl

e fr

om

2,49

3 ch

ildre

n.

Per

cent

ch

ange

of

lu

ng

func

tion

para

met

ers

acco

rdin

g to

a d

ecre

ase

of T

SP

by

50

µg/

m3

we

re

deriv

ed

by

linea

r re

gres

sion

m

odel

s af

ter

adj

ustm

ent

for

sex,

hei

ght,

sea

son,

lu

ng

func

tion

eq

uipm

ent,

pare

ntal

ed

ucat

ion,

pa

rent

al

atop

y an

d en

viro

nmen

tal

toba

cco

smok

e.

FV

C

and

FE

V1

of

the

child

ren

incr

ease

d fr

om

1992

–199

3 to

19

98–1

999.

D

ecre

men

ts o

f T

SP

(p

=0.

043)

and

SO

2 (p

=

0.02

9) w

ere

sign

ifica

ntly

ass

ocia

ted

with

an

impr

ovem

ent

of F

VC

. E

ffect

s on

FE

V1

we

re

smal

ler

and

not

sta

tistic

ally

sig

nific

ant.

50 µ

g/m

3 dec

reas

e of

TS

P.

Adj

uste

d p

erce

nt

chan

ge

(95%

C

I):

FV

C

Tot

al: 4

.7%

(0

.2, 9

.5)

Boy

s: 3

.7%

(-1

.2, 8

.8)

Girl

s: 5

.9%

(0.

8, 1

1.1)

F

EV

1

Tot

al: 2

.9%

(-1

.4, 7

.3)

Boy

s: 1

.7%

(-2

.9, 6

.6)

Girl

s: 4

.1%

(-0

.7, 9

.2).

report no. 4/11

158

Krä

mer

et

al

. (1

999)

(K

ram

er e

t al,

1999

) S

ix

Ea

st

and

Wes

t G

erm

any

com

mun

ities

(L

eipz

ig,

Hal

le,

Mad

debu

rg,

Altm

ark,

D

uisb

urg,

Bor

ken)

B

etw

een

199

1 an

d 19

95

TS

P

leve

ls

in

six

com

mun

ities

ran

ged

from

46

to

10

2.

Eac

h E

ast

Ger

man

y co

mm

unity

had

de

crea

se in

TS

P b

etw

een

19

91 a

nd 1

99

5. T

SP

wa

s m

easu

red

usin

g a

low

vo

lum

e sa

mpl

er.

The

stu

dy a

sses

sed

rela

tions

hip

betw

een

TS

P

and

airw

ay d

isea

se a

nd a

llerg

ies

by

pare

ntal

qu

estio

nnai

res

in y

ear

ly s

urve

ys o

f ch

ildre

n (5

-8

year

) be

twe

en

Feb

ruar

y an

d M

ay.

The

qu

estio

ns i

nclu

ded

pneu

mon

ia,

bron

chiti

s ev

er

diag

nose

d b

y ph

ysic

ian,

nu

mbe

r of

co

lds,

fr

eque

nt

coug

h,

alle

rgic

sy

mpt

oms.

In

al

l, 19

,090

chi

ldre

n pa

rtic

ipat

ed.

Ave

rage

res

pon

se

wa

s 87

%.

An

alys

es w

ere

cond

ucte

d on

14,

144

child

ren

for

who

m i

nfor

mat

ion

on a

ll co

varia

tes

wer

e a

vaila

ble

. V

aria

bles

in

clud

ed

gen

der;

pa

rent

ed

ucat

ion,

he

atin

g fu

el,

ET

S.

Log

istic

re

gres

sion

us

ed

to

allo

w

for

time

tren

ds

and

SO

2 an

d T

SP

effe

cts.

Re

gres

sion

coe

ffic

ient

s w

ere

con

vert

ed to

OR

s.

TS

P a

nd S

O2

sim

ulta

neou

sly

incl

uded

in t

he

mod

el.

Bro

nchi

tis e

ver

diag

nose

d sh

ow

ed

a si

gnifi

cant

ass

ocia

tion.

A d

ecre

ase

in r

aw

perc

enta

ge w

as s

een

betw

een

the

star

t of

th

e st

udy

and

th

e en

d

for

bron

chiti

s.

Bro

nchi

tis

seem

ed

to

be

asso

ciat

ed

onl

y w

ith

TS

P

in

spite

of

hu

ge

diffe

renc

es

in

mea

n S

O2

leve

ls.

Bro

nchi

tis e

ver

diag

nose

d

TS

P p

er 5

0 µ

g/m

3 O

R 1

.63

(1.3

7, 1

.93)

H

alle

(E

ast)

C

alen

dar

Ye

ar;

TS

P

(µg/

m3 );

B

ronc

hitis

19

91; 1

02; 6

0.5

1992

; 73;

54.

7

1993

; 62;

49.

6

1994

; 52;

50.

4

1995

; 46;

51.

9

Geh

ring

et

al.

(200

2)

(Geh

ring

et a

l, 20

02)

In M

unic

h, G

erm

any

Dec

embe

r 19

97

- Ja

nuar

y 19

99

Ann

ual

PM

2.5

leve

ls

dete

rmin

ed

by

40

site

s an

d a

GIS

pr

edic

tor

for

mod

el.

Mea

n P

M2.

5 an

nual

av

erag

e of

13

.4

with

ra

nge

of 1

1.90

to 2

1.90

.

Effe

ct o

f tr

affic

-rel

ated

air

pollu

tant

s. P

M2.

5 an

d N

O2

on

resp

irato

ry

heal

th

outc

omes

w

hee

ze,

coug

h,

bron

chiti

s,

resp

irato

ry

infe

ctio

ns,

and

runn

y no

se

wer

e ev

alua

ted

usin

g m

ultip

le

logi

stic

re

gres

sion

an

alys

es

of

l,756

ch

ildre

n du

ring

the

first

and

sec

ond

year

of

life

adju

stin

g fo

r po

tent

ial c

onfo

undi

ng fa

ctor

s.

The

re

wa

s so

me

ind

icat

ion

of

an

asso

ciat

ion

bet

we

en P

M2.

5 a

nd s

ympt

om

s of

co

ugh

but

not

othe

r o

utco

mes

. In

th

e se

cond

ye

ar

of

life

m

ost

ef

fect

s w

ere

atte

nuat

ed.

OR

(9

5%

CI)

fo

r a

chan

ge

in

PM

2.5

conc

entr

atio

n of

1.5

µg/

m3

Whe

eze

A

ge o

f 1 y

ear:

0.9

1 (0

.76,

1.0

9)

Age

of 2

yea

r: 0

.96

(0.8

3, 1

.12)

C

ough

with

out

infe

ctio

n

Age

of 1

yea

r: 1

.34

(1.1

1, 1

.61)

D

ry c

ough

at

nigh

t A

ge o

f 1 y

ear:

1.3

1 (1

.07,

1.6

0)

Age

of 2

yea

r: 1

.20

(1.0

2, 1

.42)

B

ronc

hitis

A

ge o

f 1 y

ear:

0.9

8 (0

.80,

1.2

0)

Age

of 2

yea

r: 0

.92

(0.7

8, 1

.09)

R

espi

rato

ry in

fect

ions

A

ge o

f 1 y

ear:

1.0

4 (0

.91,

1.1

9)

Age

of 2

yea

r: 0

.98

(0.8

0, 1

.20)

S

neez

ing

A

ge o

f 1 y

ear:

1.0

1 (0

.85,

1.2

0)

Age

of 2

yea

r: 0

.96

(0.8

2, 1

.12)

.

report no. 4/11

159

Sch

iko

wsk

i et

al. (

2005

) (S

chik

ow

ski e

t al

, 200

5)

Con

secu

tive

cr

oss-

sect

iona

l st

udie

s.

Rhi

ne-

Rhu

r B

asin

, Ger

man

y 19

85-1

994.

P

M10

ann

ual

mea

n of

43

with

ran

ge o

f 35

to 5

3

PM

10

five

year

m

ean

of

48 w

ith r

ange

of 3

9 to

56.

Thi

s st

udy

exa

min

ed

the

ef

fect

of

lo

ng-t

erm

ex

posu

re t

o P

M10

fro

m i

ndu

stry

and

tra

ffic

and

NO

2 on

CO

PD

, as

def

ined

by

lung

fun

ctio

n, i

n 4,

757

mid

dle-

aged

w

om

en

enro

lled

in

cons

ecut

ive

cros

s se

ctio

nal

stud

ies

cond

ucte

d be

twee

n 19

85

and

1994

in

th

e R

hin

e-R

uhr

Bas

in o

f G

erm

any.

NO

2 a

nd P

M10

exp

osur

e w

as

asse

ssed

by

mea

sure

men

ts d

one

in a

n 8

km

grid

, an

d tr

affic

exp

osur

e b

y di

stan

ce f

rom

the

re

side

ntia

l ad

dres

s to

the

nea

rest

maj

or r

oad

usin

g G

IS d

ata.

Lun

g fu

nctio

n w

as

dete

rmin

ed

and

CO

PD

w

as

defin

ed

by

usin

g

the

GO

LD

crite

ria.

Chr

oni

c re

spira

tory

sy

mpt

oms

and

poss

ible

co

nfou

nder

s w

ere

de

fine

d by

qu

estio

nnai

re

data

. Li

nea

r an

d lo

gist

ic

regr

essi

ons,

in

clud

ing

ran

dom

ef

fect

s w

ere

used

afte

r ad

just

men

t fo

r ag

e, s

ocio

eco

nom

ic

stat

us,

smok

ing,

env

ironm

enta

l to

bacc

o sm

oke,

oc

cupa

tiona

l ex

posu

re t

o te

mpe

ratu

re a

nd d

ust,

and

heat

ing

with

foss

il fu

els.

The

pre

vale

nce

of C

OP

D (

GO

LD s

tage

s 1

–4)

w

as

4.5

%.

CO

PD

an

d pu

lmon

ary

func

tion

wer

e

stro

nges

t af

fect

ed

by

PM

10

and

traf

fic r

elat

ed e

xpo

sure

. W

omen

liv

ing

less

tha

n 10

0 m

fro

m a

bus

y ro

ad a

lso

had

a si

gnifi

cant

ly d

ecre

ased

lun

g fu

nctio

n, a

nd

CO

PD

was

1.7

9 tim

es m

ore

likel

y th

an f

or

thos

e liv

ing

fart

her

awa

y. C

hro

nic

sym

pto

ms

as

base

d

on

ques

tionn

aire

in

form

atio

n sh

ow

ed e

ffect

s in

the

sam

e di

rect

ion,

but

le

ss p

rono

unce

d.

OR

(95

% C

I) f

or 7

µg/

m3 in

crea

se

in P

M10

(IQ

R)

A

nnua

l mea

ns

Chr

onic

br

onch

itis:

1.

00

(0.8

5,

1.18

) C

hron

ic c

ough

: 1.0

3 (0

.87,

1.2

3)

Fre

quen

t cou

gh: 1

.01

(0.9

3, 1

.10)

C

OP

D:

1.37

(0.

98, 1

.92)

F

EV

1: 0

.953

(0.

916,

0.9

89)

FV

C: 0

.966

(0

.940

, 0.9

92)

Fiv

e ye

ar m

eans

C

hron

ic

bron

chiti

s:

1.13

(0

.95,

1.

34)

Chr

onic

cou

gh: 1

.11

(0.9

3, 1

.31)

F

requ

ent c

ough

: 1.0

5 (0

.94,

1.1

7)

CO

PD

: 1.

33 (

1.03

, 1.7

2)

FE

V1:

0.9

49 (

0.92

3, 0

.975

) F

VC

: 0.9

63 (

0.9

45, 0

.982

).

Pol

at e

t al.

(20

02)

(Pol

at e

t al,

2002

) 4

mon

th

cros

s-se

ctio

nal

surv

ey i

n 4

loca

tions

(A

, B

1, B

2, C

) of

3 c

ities

in

Nor

drhe

in-W

est

fale

n,

Ger

man

y F

eb 2

000

to M

ay 2

000.

T

SP

mea

n (

SD

) Lo

catio

n

A: 4

9.1

(23.

9)

Loca

tion

B1:

78.

5 (2

9.8)

Lo

catio

n B

2: 4

6.7

(19.

3)

Loca

tion

C: 3

4.9

(12

.6.)

.

At

4 lo

catio

ns,

in 3

diff

eren

t ci

ties

of N

ordr

hein

-W

estfa

len,

TS

P,

O3,

NO

x an

d S

O2

wer

e d

eriv

ed

from

co

mpl

ianc

e m

easu

rem

ents

by

go

vern

men

tal

offic

es,

and

88

4 su

bjec

ts

(501

m

othe

rs a

nd 3

83 c

hild

ren,

6 ±

7 y

ears

old

) w

ere

scre

ened

usi

ng

nasa

l la

vag

e. A

utho

rs s

tudi

ed a

po

tent

ial a

sso

ciat

ion

betw

een

ambi

ent

exp

osur

e in

the

4 lo

catio

ns a

nd n

asal

infla

mm

atio

n in

a 4

-m

onth

s cr

oss-

sect

iona

l sur

vey.

No

sign

ifica

nt d

iffer

ence

s in

tot

al c

ell c

oun

ts

or

perc

enta

ge

of

neut

rop

hils

w

ere

fo

und

be

twee

n m

othe

rs

or

child

ren

from

th

e 4

diffe

rent

lo

catio

ns,

desp

ite

smal

l b

ut

sign

ifica

nt d

iffer

ence

s in

am

bien

t ex

posu

re

to

TS

P,

SO

2,

O3,

a

nd

N

Ox

duri

ng

this

pe

riod.

No

estim

ates

fo

r T

SP

w

ere

pr

ovid

ed.

report no. 4/11

160

Wol

f (20

02)

(Wol

f, 20

02)

1,43

5 pa

tient

s tr

eate

d fo

r rh

inos

inus

itis

in a

hos

pita

l of

Col

ogne

, 199

0-19

99.

Ann

ual

mea

n of

T

SP

(1

998)

: 39.

The

stu

dy i

nves

tigat

ed t

he a

ssoc

iatio

n b

etw

een

ai

r po

llutio

n an

d ch

roni

c rh

inos

inus

itis

in

Col

ogne

, G

erm

any.

Add

ress

es o

f 1,

435

pat

ient

s tr

eate

d fo

r ch

roni

c rh

inos

inus

itis

at

the

Oto

rhin

olar

yngo

logy

D

epar

tmen

t of

th

e U

nive

rsity

H

osp

ital

of

Col

ogn

e be

twee

n

1990

an

d 19

99 w

ere

assi

gned

to

one

of t

he 8

5 ci

ty

dist

ricts

. T

SP

, S

O2

an

d

NO

x w

ere

lin

ked

to

thes

e ar

eas.

A c

ombi

ned

ind

icat

or o

f ai

r qu

ality

w

as

deriv

ed

from

th

e th

ree

cons

ider

ed

mea

sure

s. R

egr

essi

on a

naly

ses

wer

e co

mpu

ted

adju

stin

g fo

r so

cioe

cono

mic

le

vel

of

the

85

dist

ricts

.

A

wea

k b

ut

cons

iste

nt

rela

tion

betw

een

m

ore

pollu

ted

are

as a

nd t

he

prev

alen

ce o

f ch

roni

c rh

inos

inus

itis

was

foun

d.

No

estim

ates

fo

r T

SP

w

ere

pr

ovid

ed.

FRA

NC

E

Bal

di e

t al

. (1

999)

(B

aldi

et

al,

1999

) 24

are

as o

f se

ven

Fre

nch

tow

ns,

197

4-1

976.

P

ollu

tant

s: T

SP

, B

S,

and

S

O2,

NO

4

3-ye

ar

aver

age

TS

P-

mea

n an

nual

va

lues

ra

ngin

g be

twee

n 45

and

24

3. T

SP

wa

s m

easu

red

by

the

gr

avim

etric

m

etho

d.

Rea

naly

sis

of P

ollu

tion

Atm

osph

eric

of

Aff

ectio

n R

espi

rato

ry C

hron

ique

s (P

AA

RC

) su

rve

y da

ta

to

sear

ch

for

rela

tions

hips

be

twee

n

mea

n an

nual

ai

r po

lluta

nt

leve

ls

and

prev

alen

ce

of

asth

ma

in

1291

ad

ult

(25-

59

year

s)

and

195

child

ren

(5-9

yea

rs)

asth

mat

ics.

Ran

dom

effe

cts

logi

stic

re

gre

ssio

n m

odel

us

ed

and

incl

uded

ag

e, s

mok

ing,

and

edu

catio

n le

vel

in t

he f

inal

m

odel

.

Onl

y an

as

soci

atio

n be

twee

n S

O2

and

asth

ma

in

adul

ts

obse

rved

. N

o ot

her

pollu

tant

w

as

asso

ciat

ed.

N

or

was

re

latio

nshi

p

with

ch

ildre

n se

en.

Met

eoro

logi

cal

varia

bles

an

d O

3 no

t ev

alua

ted.

For

a 5

0 µ

g/m

3 incr

ease

in T

SP

A

dult

asth

ma

prev

alen

ce

OR

1.0

1 (0

.92

, 1.1

1)

Zeg

hnou

n et

al

. (1

999)

(Z

eghn

oun

et a

l, 19

99)

La H

avre

, F

ranc

e, 1

993-

1996

. D

aily

m

ean

B

S

leve

ls

mea

sure

d in

th

ree

stat

ions

ra

nged

be

twee

n

12 a

nd 1

4.

Res

pira

tory

dr

ug

sale

s fo

r m

ucol

ytic

an

d an

ticou

gh

me

dica

tions

(m

ost

pr

escr

ibed

by

a

phys

icia

n) w

ere

eval

uate

d ve

rsus

BS

, S

O2,

and

N

O2

leve

ls.

An

auto

regr

essi

ve

Poi

sson

re

gres

sion

m

odel

pe

rmitt

ing

over

disp

ersi

on

cont

rol w

as u

sed

in th

e an

alys

is.

Res

pira

tory

dru

g sa

les

asso

ciat

ed w

ith B

S,

NO

2,

and

SO

2 le

vels

. B

oth

an

early

re

spon

se (

0 to

3 d

ay l

ag)

and

a lo

nger

one

(la

gs o

f 6 a

nd 9

day

s) w

ere

asso

ciat

ed.

—

report no. 4/11

161

Pen

ard-

Mor

and

et

al.

(200

5);

(Pen

ard-

Mor

and

et a

l, 20

05)

ISA

AC

II

Stu

dy,

6,67

2 sc

hool

child

ren

fr

om

six

Fre

nch

citie

s,

Enr

ollm

ent:

Mar

ch

1999

-O

ctob

er 2

000.

E

xpos

ure:

199

8-20

00.

3-ye

ar-a

vera

ged

conc

entr

atio

n

of

PM

10,

22.

The

pre

sent

cro

ss-s

ectio

nal

stud

y an

alys

ed t

he

asso

ciat

ions

be

twee

n lo

ng-t

erm

ex

posu

re

to

back

grou

nd

air

pollu

tion

an

d at

opic

an

d re

spira

tory

out

com

es i

n 6,

672

sch

oolc

hild

ren

aged

9–1

1 ye

ars

recr

uite

d fr

om 1

08 r

ando

mly

sc

hool

s in

six

Fre

nch

citie

s. C

hild

ren

unde

rwen

t a

clin

ical

exa

min

atio

n in

clu

ding

a s

kin

pric

k te

st

(SP

T)

to

com

mon

al

lerg

ens,

ex

erci

se-in

duce

d br

onch

ial

reac

tivity

(E

IB)

and

skin

exa

min

atio

n fo

r fle

xura

l de

rmat

itis.

T

he

prev

alen

ce

of

asth

ma,

al

lerg

ic

rhin

itis

and

at

opic

de

rmat

itis

wa

s as

sess

ed

by

a st

anda

rdiz

ed

heal

th

ques

tionn

aire

com

plet

ed b

y th

e pa

rent

s. T

hree

-ye

ar-a

vera

ged

conc

entr

atio

ns

of

air

pollu

tant

s (N

O2,

S

O2,

P

M10

an

d O

3)

wer

e

calc

ulat

ed

at

child

ren’

sc

hoo

ls

usin

g m

easu

rem

ents

of

ba

ckgr

ound

m

onito

ring

stat

ions

. O

Rs

wer

e

deriv

ed b

y m

ultip

le l

ogis

tic r

egre

ssio

n m

odel

s af

ter

adju

stm

ent

for

age,

sex

, fa

mily

his

tory

of

alle

rgy,

pa

ssiv

e sm

okin

g an

d pa

rent

eral

ed

ucat

ion.

EIB

, lif

etim

e as

thm

a an

d lif

etim

e al

lerg

ic

rhin

itis

wer

e

dire

ctly

as

soci

ated

to

an

in

crea

se i

n th

e ex

posu

re t

o S

O2,

PM

10 a

nd

O3.

M

oreo

ver,

S

PT

po

sitiv

ity

was

as

soci

ated

with

O3.

A

ssoc

iatio

ns w

ith p

ast

year

sym

ptom

s w

ere

cons

iste

nt,

even

if

not

alw

ays

stat

istic

ally

si

gnifi

cant

. R

esul

ts

pers

iste

d in

lo

ng-t

erm

re

side

nt

(cur

rent

ad

dres

s fo

r at

le

ast

8 ye

ars)

ch

ildre

n.

Aut

hors

co

nclu

ded

that

a

mod

erat

e in

crea

se i

n lo

ng-t

erm

exp

osur

e t

o ba

ckgr

ound

am

bien

t ai

r po

llutio

n w

as

asso

ciat

ed w

ith a

n in

crea

sed

prev

alen

ce o

f re

spira

tory

and

ato

pic

indi

cato

rs in

chi

ldre

n.

OR

(95

% C

I) f

or a

n in

crem

ent

of

PM

10 b

y 10

µg

/m3 :

Dur

ing

the

clin

ical

exa

min

atio

n E

IB: 1

.43

(1.0

2, 2

.01)

F

lexu

ral

derm

atiti

s:

0.79

(0

.59,

1.

07)

Pas

t yea

r W

heez

e: 1

.05

(0.7

2, 1

.54)

A

sthm

a: 1

.23

(0.7

7, 1

.95)

R

hino

conj

unct

iviti

s:

1.17

(0

.86,

1.

59)

Ato

pic

derm

atiti

s:

1.28

(0

.96,

1.

71)

Life

time

Ast

hma:

1.3

2 (0

.96,

1.8

1)

Alle

rgic

rhi

nitis

: 1.3

2 (1

.04,

1.6

8)

Ato

pic

derm

atiti

s:

1.09

(0

.88,

1.

36)

Ato

py: 0

.98

(0.8

0, 1

.22)

P

olle

n: 1

.14

(0.8

5, 1

.53)

In

door

: 0.9

1 (0

.72,

1.1

5)

Mou

lds:

1.0

0 (0

.53,

1.8

8).

SWIT

ZER

LAN

D

A

cker

man

n-Li

ebric

h et

al.

(199

7)

(Ack

erm

ann-

Lieb

rich

et a

l, 19

97)

Eig

ht S

wis

s re

gion

s P

ollu

tant

s:

SO

2,

NO

2,

TS

P, O

3, a

nd P

M10

. P

M w

as m

easu

red

with

a

Har

vard

impa

ctor

. P

M10

ra

nged

fr

om

10

to

53 w

ith a

mea

n of

37.

Long

-ter

m

effe

cts

of

air

pollu

tion

stud

ied

in

cros

s-se

ctio

nal

popu

latio

n-ba

sed

sam

ple

of

adul

ts a

ged

18 t

o 60

yea

rs.

Ran

dom

sam

ple

of

2,50

0 ad

ults

in

ea

ch

regi

on

dra

wn

fr

om

regi

strie

s of

loca

l inh

abita

nts.

Nat

ural

loga

rith

ms

of

FV

C

and

FE

V1

regr

esse

d ag

ains

t n

atur

al

loga

rithm

s of

hei

ght,

wei

ght

, ag

e, g

ende

r, a

topi

c st

atus

, and

po

lluta

nt v

aria

ble

s.

Sig

nific

ant

an

d co

nsis

tent

ef

fect

s on

FV

C

and

FE

V

wer

e fo

und

for

PM

10,

NO

2 a

nd

SO

2.

Est

imat

ed

regr

essi

on

coef

ficie

nt

for

PM

10 v

ersu

s F

VC

: -

0.03

5 (-

0.04

1, -

0.02

8).

Cor

resp

ondi

ng

valu

e fo

r F

EV

1:

-0.0

16

(-0.

023,

-0

.01)

. T

hus,

10

µ

g/m

3 P

M10

inc

reas

e es

timat

ed t

o le

ad

to

estim

ated

3.

4 pe

rcen

t de

crea

se i

n F

VC

and

1.6

per

cent

de

crea

se in

FE

V1.

report no. 4/11

162

Bra

un-F

ahrlä

nder

et

al

. (1

997)

(B

raun

-Fah

rland

er

et a

l, 19

97)

10 S

wis

s co

mm

uniti

es

Pol

luta

nts:

P

M10

, N

O2,

S

O2,

and

O3.

P

M w

as m

easu

red

with

a

Har

vard

impa

ctor

. P

M10

ra

nged

fr

om

10

to

33.

Impa

cts

of l

ong-

term

air

pollu

tion

exp

osur

e on

re

spira

tory

sy

mpt

oms

and

illne

sses

w

ere

ev

alua

ted

in

cros

s-se

ctio

nal

stud

y of

S

wis

s sc

hool

ch

ildre

n,

(age

d 6

to

15

year

s).

Sym

ptom

s an

alyz

ed u

sing

a l

ogis

tic r

egre

ssio

n m

odel

inc

ludi

ng c

ovar

iate

s of

fam

ily h

isto

ry o

f re

spira

tory

an

d al

lerg

ic

dise

ases

, nu

mbe

r of

si

blin

gs,

pare

ntal

ed

ucat

ion,

in

door

fu

els,

pa

ssiv

e sm

okin

g, a

nd o

ther

s.

Res

pira

tory

e

ndpo

ints

of

ch

roni

c co

ugh,

br

onch

itis,

w

heez

e an

d co

njun

ctiv

itis

sym

ptom

s w

ere

al

l re

late

d

to

the

va

rious

po

lluta

nts.

The

col

inea

rity

of t

he p

ollu

tant

s in

clud

ing

NO

2,

SO

2, a

nd O

3,

prev

ente

d an

y ca

usal

sep

ara

tion.

PM

10

Chr

onic

co

ugh

O

R

11.4

(2

.8,

45.5

) B

ronc

hitis

OR

23.

2 (2

.8, 4

5.5)

W

heez

e O

R 1

.41

(0.5

5, 3

.58)

Bay

er-O

gles

by

et

al.

(200

5) (

Bay

er-O

gles

by e

t al

, 200

5)

9,59

1 ch

ildre

n fr

om

9 S

wis

s co

mm

uniti

es,

1992

-200

1.

PM

10

rang

ed

from

10

to

47

.

The

pre

sent

cro

ss-s

ectio

nal

stud

y in

vest

igat

ed

whe

ther

a

rath

er

mod

erat

e de

clin

e

of

air

pollu

tion

leve

ls i

n th

e 19

90s

in S

witz

erla

nd w

as

asso

ciat

ed

with

a

redu

ctio

n in

re

spira

tory

sy

mpt

oms

and

dise

ases

in

9,

591

scho

ol

child

ren

of

nine

S

wis

s co

mm

uniti

es

betw

een

1992

and

200

1. P

aren

ts o

f ch

ildre

n co

mp

lete

d id

entic

al

que

stio

nnai

res

on

heal

th

stat

us

and

cova

riate

s.

We

assi

gned

to

ea

ch

child

an

es

timat

e of

re

gion

al

PM

10

and

dete

rmin

ed

chan

ge

in

PM

10

sinc

e th

e fir

st

surv

ey.

OR

s as

soci

ated

with

a d

eclin

e of

10

µg/

m3 i

n P

M10

w

ere

de

rived

af

ter

a pr

iori

adju

stm

ent

fo

r so

cioe

cono

mic

fa

ctor

s,

heal

th

rela

ted

fact

ors,

in

clud

ing

fam

ily

hist

ory

of

asth

ma,

br

onch

itis

and

atop

y,

indo

or

fact

ors,

in

clud

ing

sm

okin

g st

atus

of

the

mot

her,

and

avo

idan

ce b

ehav

iour

w

ith r

espe

ct to

alle

rgie

s.

PM

10

was

di

rect

ly

asso

ciat

ed

with

pr

eval

ence

o

f ch

roni

c co

ugh,

br

onch

itis,

co

mm

on

cold

, no

ctur

nal

dry

coug

h,

and

conj

unct

iviti

s sy

mpt

oms.

C

hang

es

in

prev

alen

ce

of

snee

zing

du

ring

polle

n se

ason

, as

thm

a,

and

hay

feve

r w

ere

not

asso

ciat

ed w

ith P

M10

.

Adj

uste

d O

R (

95%

CI)

for

a 1

0-µ

g/m

3 dec

line

of P

M10

: C

hron

ic c

ough

: 0.6

5 (0

.54,

0.7

9)

Bro

nchi

tis: 0

.66

(0.5

5, 0

.80)

C

omm

on c

old:

0.7

8 (0

.68,

0.8

9)

Noc

turn

al d

ry c

ough

: 0.

70 (

0.60

, 0.

83)

Con

junc

tiviti

s: 0

.81

(0.7

0, 0

.95)

W

heez

e: 0

.8,

NS

S

neez

ing:

0.9

, N

S

Ast

hma:

1.0

, N

S

Hay

feve

r: 1

.0, N

S.

report no. 4/11

163

Bay

er-O

gles

by

et

al.

(200

6) (

Bay

er-O

gles

by e

t al

, 200

6)

SA

PA

LDIA

co

hort

, S

witz

erla

nd, 1

991-

2002

. P

M10

mea

n: 2

1.4.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

livin

g ne

ar

mai

n st

reet

s an

d re

spira

tory

sy

mpt

oms

usin

g th

e S

wis

s C

ohor

t S

tudy

on

Air

Pol

lutio

n an

d Lu

ng

Dis

ease

s in

A

dults

(S

AP

AL

DIA

) co

hort

. S

AP

ALD

IA

1 w

as

cond

ucte

d in

199

1. I

n 20

02

subj

ects

wer

e re

-in

terv

iew

ed

(SA

PA

LD

IA

2).

The

pr

esen

t an

alys

es

wer

e ba

sed

on

a to

tal

of

12,9

99

obse

rvat

ions

fro

m 8

,555

sub

ject

s. G

eog

raph

ic

info

rmat

ion

syst

em d

ata

wer

e us

ed t

o as

sign

in

divi

dual

tr

affic

e

xpos

ure

es

timat

es

at

each

su

bjec

t’s r

esid

ence

. T

he g

ener

aliz

ed e

stim

atin

g eq

uatio

n re

gres

sion

mod

els

wer

e de

rive

d af

ter

adju

stm

ent

for

vario

us

fact

ors,

in

clud

ing

se

x,

age,

ed

ucat

ion,

ac

tive

and

pa

ssiv

e sm

okin

g,

occu

patio

nal

expo

sure

, re

gion

al

back

grou

nd

PM

10 (

estim

ated

by

a di

sper

sion

mod

el,

usin

g 44

mon

itorin

g si

tes

in S

witz

erla

nd i

n 20

00 )

and

heal

th r

elat

ed f

acto

rs,

Sub

ject

s liv

ing

near

bus

y st

reet

s re

port

ed

mor

e fr

eque

ntly

res

pira

tory

sym

ptom

s. T

his

leav

es

open

th

e qu

estio

n w

heth

er

the

prev

alen

ce o

f br

onch

itis

sym

ptom

s is

due

to

“long

-ter

m

effe

ct”

or

refle

cts

the

acut

e ef

fect

s of

air

pollu

tion

in lo

nger

per

iods

.

No

estim

ates

for

PM

10.

Zem

p et

al.

(199

9) (

Zem

p

et a

l, 19

99)

8 st

udy

site

s in

S

witz

erla

nd.

Pol

luta

nts:

T

SP

, P

M1

0,

SO

2, N

O2,

and

O3.

P

M w

as m

easu

red

with

a

Har

vard

impa

ctor

. P

M10

ra

nged

fr

om

10

to

33 w

ith a

mea

n of

21.

Logi

stic

re

gres

sion

an

alys

is

of

asso

ciat

ions

be

twee

n pr

eval

ence

s of

re

spira

tory

sym

ptom

s in

ran

dom

sam

ple

of a

dults

and

air

pollu

tion.

R

egre

ssio

ns

adju

sted

fo

r ag

e,

BM

I,

gen

der,

pa

rent

al

asth

ma,

ed

ucat

ion,

an

d fo

reig

n ci

tizen

ship

.

Chr

onic

co

ugh

and

chro

nic

phle

gm

and

brea

thle

ssne

ss w

ere

rela

ted

to T

SP

, P

M10

an

d N

O2.

Chr

onic

co

ugh,

ch

roni

c p

hleg

m

and

brea

thle

ssne

ss w

ere

rela

ted

to P

M10

, and

TS

P.

AU

STR

IA

Hor

ak

et

al.

(200

2)

(Hor

ak e

t al,

2002

) F

risch

er

et

al.

(199

9)

(Fris

cher

et a

l, 19

99)

Eig

ht

com

mun

ities

in

lo

wer

A

ustr

ia

betw

een

19

94-1

997.

P

M10

m

ean

su

mm

er

valu

e of

17

.36

an

d w

inte

r va

lue

of 2

1.03

.

Lung

fun

ctio

n as

sess

ed in

975

sch

oolc

hild

ren

in

grad

e 2-

3.

A

seve

ral

step

an

alys

is

incl

uded

G

EE

an

d se

nsiti

vity

ana

lyse

s.

Con

clud

ed t

hat

lon

g te

rm e

xpos

ure

to P

M10

ha

d a

sign

ifica

nt

nega

tive

ef

fect

on

lu

ng

func

tion

with

ad

ditio

nal

evid

ence

fo

r a

furt

her

effe

ct fo

r O

3 an

d N

O2.

Afte

r ad

just

ing

for

con

foun

ders

an

incr

ease

in P

M10

by

10 µ

g/m

3 was

as

soci

ated

w

ith

a de

crea

se

in

FE

V1

gro

wth

at

84 m

L/yr

and

329

m

L/s

year

for

ME

F25

-75.

report no. 4/11

164

GR

EEC

E

Kar

akat

sani

et

al.

(200

3)

(Kar

akat

sani

et a

l, 20

03)

Nes

ted

case

-con

trol

st

udy

of t

he E

PIC

stu

dy,

Ath

ens,

Gre

ece.

B

S f

or t

he m

ost

pollu

ted

area

ra

nged

fr

om

34

to

79.

A c

ase–

cont

rol s

tudy

nes

ted

in t

he E

PIC

coh

ort,

unde

rtak

en i

n A

then

s, G

reec

e, w

as

con

duct

ed

in

orde

r to

ex

amin

e th

e a

ssoc

iatio

n be

twee

n lo

ng-t

erm

exp

osur

e to

am

bien

t ai

r po

llutio

n an

d th

e ris

k of

ch

roni

c br

onch

itis,

em

phys

em

a or

C

OP

D.

Ove

rall,

16

8 pa

rtic

ipan

ts

repo

rtin

g a

hist

ory

of

CO

PD

sy

mpt

om

atol

ogy

and

168

heal

thy

cont

rols

in

divi

dua

lly

mat

ched

fo

r ag

e an

d ge

nder

, w

ere

vis

ited

by

a ph

ysic

ian

at t

heir

hom

es f

or c

ondu

ctin

g sp

irom

etry

and

a m

edic

al

inte

rvie

w.

Indi

vidu

aliz

ed

pers

onal

e

xpos

ure

to

air

pollu

tion

was

ass

esse

d on

the

bas

is o

f lo

ng-

term

res

iden

tial a

nd o

ccup

atio

nal s

ubje

ct h

isto

ry

linke

d w

ith

geog

raph

ical

ai

r po

llutio

n

dist

ribut

ion.

Cas

es w

ere

mor

e ex

pose

d to

air

pollu

tion

com

pare

d to

con

trol

s, w

ith O

Rs

for

sub

ject

s in

th

e h

ighe

st

quar

tile

of

expo

sure

vs

al

l ot

hers

in

clud

ed

betw

een

1.46

an

d 2.

01.

Aut

hors

con

clud

ed t

hat

long

-ter

m e

xpos

ure

to a

ir po

llutio

n w

as a

n im

port

ant

fact

or i

n th

e de

velo

pm

ent

of

chro

nic

resp

irato

ry

dise

ases

.

No

estim

ates

on

PM

.

Sic

hlet

idis

et

al

. (2

005)

(S

ichl

etid

is e

t al

, 200

5)

2000

-200

1. C

hild

ren

from

fiv

e ci

ties

of

Wes

tern

M

aced

onia

, G

reec

e (t

hree

with

inf

orm

atio

n on

T

SP

and

PM

10).

T

SP

mea

n:

Pto

lem

aida

: 132

K

ozan

i: 88

F

lorin

a: 5

6 P

M10

mea

n:

Pto

lem

aida

: 86.

3 K

ozan

i: 64

.2

Flo

rina:

58.

3.

Thi

s st

udy

com

pare

s pr

eval

ence

of

rhin

itis

and

bron

chiti

s in

5

diffe

rent

ci

ties

of

Wes

tern

M

aced

onia

ch

arac

teriz

ed b

y di

ffere

nt t

ype

and

leve

l of

en

viro

nmen

tal

pollu

tion.

D

urin

g

2000

an

d 20

01 3

,559

chi

ldre

n ag

ed 9

-12

year

s w

ere

enro

lled

in

the

stud

y.

Con

cent

ratio

ns

of

TS

P

and

PM

10 w

ere

mea

sure

d in

3 c

ities

onl

y.

Sym

ptom

s fr

om

the

uppe

r an

d lo

wer

re

spira

tory

sy

stem

w

ere

mor

e fr

eque

nt

in

child

ren

livin

g in

mor

e po

llute

d ar

eas.

No

estim

ates

for

PM

report no. 4/11

165

POLA

ND

Jedr

ycho

wsk

i et

al

. (1

999)

(J

edry

cho

wsk

i et

al

, 199

9)

In

Kra

kow

, P

olan

d in

19

95 a

nd 1

997

Spa

cial

di

strib

utio

ns

for

BS

and

SO

2 d

eriv

ed

from

ne

twor

k of

17

ai

r m

onito

ring

stat

ions

. BS

52

.6 µ

g/m

± 5

3.98

in h

igh

ar

ea a

nd

33.2

3 ±

35.9

9 in

low

are

a.

Effe

cts

on

lung

fu

nctio

n

grow

th

stu

died

in

pr

eado

lesc

ent

child

ren.

Lu

ng

func

tion

grow

th

rate

mea

sure

d by

gai

n in

FV

C a

nd F

EV

1 an

d oc

curr

ence

of

slo

w lu

ng f

unct

ion

grow

th (

SLF

G)

over

the

2 y

ear

perio

d de

fined

as

low

est

qui

ntile

of

th

e di

strib

utio

n of

a

gi

ven

test

in

g

ende

r gr

oup.

1,1

29 c

hild

ren

age

9 pa

rtic

ipat

ed i

n fir

st

year

and

1,0

01

in f

ollo

w-u

p 2

yea

rs l

ater

. A

TS

st

anda

rd q

uest

ionn

aire

and

PF

T m

etho

ds u

sed.

In

itial

ly

univ

aria

te

desc

ript

ive

stat

istic

s of

pu

lmon

ary

func

tion

indi

ces

and

SLF

G

wer

e

esta

blis

hed,

fo

llow

ed

by

mul

tivar

iate

lin

ear

regr

essi

on

ana

lyse

s in

clu

ding

ge

nder

, E

TS

, pa

rent

al e

duca

tion,

hom

e he

atin

g sy

ste

m a

nd

mol

d. S

O2

wa

s al

so a

naly

zed.

Sta

tistic

ally

sig

nific

ant

nega

tive

asso

ciat

ion

betw

een

air

pollu

tion

leve

l and

lung

fun

ctio

n gr

owth

(F

VC

and

FE

V1)

ove

r th

e fo

llow

up

in

both

ge

nder

gr

oups

. S

LFG

w

as

sign

ifica

ntly

hi

gher

in

th

e m

ore

pollu

ted

area

s on

ly a

mon

g bo

ys.

In g

irls

ther

e w

as

cons

iste

ncy

in t

he d

irect

ion

of t

he e

ffect

, bu

t no

t st

at.

sign

ifica

nt.

Cou

ld n

ot s

epar

ate

BS

an

d S

O2

effe

cts

on

lung

fu

nctio

n gr

ow

th.

Exc

ludi

ng

asth

ma

subj

ects

su

b-sa

mpl

e (s

ize

917)

pro

vide

d si

mila

r re

sults

.

Boy

s S

LFG

(F

VC

) O

R: 2

.15

(1.2

5, 3

.69)

S

LFG

(F

EV

1)

OR

: 1.9

0 (1

.12,

3.2

5)

Girl

s F

VC

OR

: 1.5

0 (

0.84

, 2.6

8)

FE

V1

OR

: 1.3

9 (0

.78,

2.4

4)

Jedr

ycho

wsk

i an

d F

lak

(199

8)

(Jed

rych

ow

ski

andF

lak,

199

8)

In

Kra

cow

P

olan

d,

in

1991

-199

5 D

aily

24

h co

ncen

trat

ion

of S

PM

(bl

ack

smok

e)

mea

sure

d at

17

ai

r m

onito

ring

stat

ions

. H

igh

area

s ha

d 52

.6

mea

n co

mpa

red

to

low

are

as a

t 33.

2.

Res

pira

tory

he

alth

su

rvey

of

1,

129

scho

ol

child

ren

(age

d 9

year

).

Res

pira

tory

ou

tcom

es

incl

uded

ch

roni

c co

ugh,

ch

roni

c ph

legm

, w

heez

ing,

diff

icul

ty b

reat

hin

g an

d as

thm

a. M

ulti-

varia

ble

logi

stic

re

gres

sion

us

ed

to

calc

ulat

e pr

eval

ence

O

R

for

sym

ptom

s ad

just

ed

for

pote

ntia

l con

foun

ding

.

The

co

mpa

rison

of

a

djus

ted

effe

ct

estim

ates

re

veal

ed

chro

nic

ph

legm

as

un

ique

sym

ptom

rel

ated

nei

ther

to

alle

rgy

nor

to i

ndoo

r va

riabl

e bu

t w

as

asso

ciat

ed

sign

ifica

ntly

w

ith

outd

oor

air

pollu

tion

cate

gory

(A

PL)

. N

o po

tent

ial

conf

ound

ing

varia

ble

had

maj

or e

ffect

.

It w

as

not

poss

ible

to

as

sess

se

para

tely

the

con

trib

utio

n of

the

di

ffere

nt s

ourc

es o

f a

ir po

lluta

nts

to

the

occu

rren

ce

of

resp

irato

ry

sym

ptom

s.

ET

S

and

hous

ehol

d he

atin

g (c

oal

vs.

gas

vs.

cent

ral

heat

ing)

ap

pea

red

to

be

of

min

imal

impo

rtan

ce.

BU

LGA

RIA

T

urno

vska

an

d K

ostir

anev

(1

999)

(T

urno

vska

T

an

dKos

tiane

v S

, 199

9)

Dim

itrov

grad

, B

ulga

ria,

May

199

6 T

SP

m

ean

leve

ls

wer

e

520

± 16

1 in

19

86

and

187

± 9

in

1996

. S

O2,

H

2S,

and

N

O2

also

m

easu

red.

Res

pira

tory

fun

ctio

n of

97

scho

olch

ildre

n (m

ean

age

10.4

± 0

.6 y

ear)

mea

sure

d in

May

199

6 as

a

sam

ple

of

12%

of

al

l fo

ur-g

rade

rs

in

Dim

itrov

grad

. T

he

obta

ined

re

sults

w

ere

co

mpa

red

with

ref

eren

ce v

alue

s fo

r B

ulga

rian

child

ren

aged

7 t

o 14

yea

r, c

alcu

late

d in

the

sa

me

labo

rato

ry

in

1986

. V

aria

tion

ana

lysi

s te

chni

ques

we

re u

sed

to tr

eat t

he d

ata.

Vita

l ca

paci

ty a

nd F

EV

1 w

ere

sign

ifica

ntly

lo

wer

(m

ean

valu

e. =

88.

54%

and

82.

5%

re

spec

tfully

) co

mpa

ring

valu

es

betw

een

19

86

and

1996

. T

SP

ha

d de

crea

sed

by

2.74

tim

es

to

leve

ls

still

hi

gher

th

an

Bul

garia

n an

d W

HO

sta

ndar

ds.

—

report no. 4/11

166

TAB

LE IX

- LO

NG

TER

M P

AR

TIC

ULA

TE M

ATT

ER E

XPO

SUR

E A

ND

CA

NC

ER.

Ref

eren

ce, L

ocat

ion,

Ye

ars,

PM

Inde

x, M

ean

or M

edia

n (µ

g/m

3 ).

Stud

y D

escr

iptio

n. M

etho

ds, c

o-p

ollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

. PM

Inde

x, R

R (9

5% C

I)

EPIC

Vin

eis

et a

l., 2

006

(Vin

eis

et a

l, 20

06);

Vin

eis

et a

l.,

2007

(V

inei

s e

t al,

2007

) N

este

d ca

se-c

ontr

ol

stud

y (2

71

case

s,

737

mat

ched

co

ntro

ls)

in

the

EP

IC

coh

ort;

10

coun

trie

s.

Rec

ruitm

ent

perio

d:

1993

-199

8 M

edia

n fo

llow

-up:

7

ye

ars.

P

M10

be

twee

n 19

.9

(Ile

de

F

ranc

e 19

95-1

999)

an

d 73

.4

(Tur

in

1990

-19

94).

In a

nes

ted

cas

e-co

ntro

l st

udy

of t

he E

uro

pean

P

rosp

ectiv

e S

tudy

in

to

Can

cer

and

Nut

ritio

n (E

PIC

) co

hort

, ba

sed

on

mor

e th

an

500

,000

he

alth

y vo

lunt

eers

ag

ed

35-7

4 fr

om

10

Eur

opea

n co

untr

ies,

27

1 ex

-sm

oker

(s

ince

at

le

ast

10 y

ears

) an

d ne

ver

smok

er c

ases

with

lu

ng c

ance

r o

ccur

red

in a

med

ian

follo

w-u

p of

7

year

s. C

ases

wer

e co

mpa

red

with

737

co

ntro

ls

freq

uenc

y m

atch

ed

by

age,

sm

okin

g st

atus

, co

untr

y an

d tim

e be

twe

en

recr

uitm

ent

and

diag

nosi

s. I

n o

rder

to

asse

ss t

he e

xpos

ure

to

traf

fic-r

elat

ed a

ir po

llutio

n, t

he h

ome

addr

ess

at

the

time

of

enro

llmen

t w

as

cons

ider

ed.

B

oth

dist

ance

s to

a m

ajor

str

eet

and

annu

al a

vera

ge

conc

entr

atio

ns

of P

M1

0 (a

vaila

ble

for

113

cas

es

and

312

cont

rols

) an

d ot

her

co-p

ollu

tant

s,

incl

udin

g N

O2,

O3

and

SO

2,

wer

e co

nsid

ered

. O

Rs

wer

e de

rived

by

co

nditi

onal

lo

gist

ic

regr

essi

on m

odel

s af

ter

furt

her

adju

stm

ent

for

educ

atio

n, B

MI,

phys

ical

act

ivity

, en

ergy

int

ake,

fr

uit,

vege

tabl

es,

mea

t an

d al

coho

l co

nsum

ptio

n.

Fur

ther

m

odel

s in

clu

de

cotin

ine

leve

ls a

nd o

ccup

atio

nal i

nde

x.

No

sign

ifica

nt a

ssoc

iatio

ns w

ere

foun

d fo

r in

crem

ents

by

10

μg

/m3

of

PM

10,

NO

2 (O

R=

1.14

; 95

%

CI:

0.

78-1

.67)

an

d S

O2.

(O

R=

1.08

; 9

5%

CI:

0.

89-

1.30

).

So

me

exce

ss r

isks

wer

e fo

und

whe

n co

nsid

erin

g th

e th

ird

vs

the

othe

r tw

o te

rtile

s of

ex

posu

re

to

NO

2 (O

Rs

rang

ed

betw

een

1.

30 a

nd 1

.62

acc

ordi

ng t

o va

rious

mod

els;

P

AR

%=

5%

), b

ut n

ot t

o P

M10

and

SO

2. T

he

OR

of

livin

g n

earb

y he

avy

traf

fic r

oads

was

1.

46 (

95%

CI:

0.8

9-2.

40),

cor

resp

ondi

ng t

o a

PA

R%

of

7%

.

Adj

uste

d O

R f

or i

ncre

men

ts o

f 10

μg/

m3 o

f P

M10

: 0.

91 (

0.7

0,

1.18

).

OR

for

the

up

per

vs t

he l

ow

est

an

d th

e in

term

edia

te

tert

iles

(i.e.

, ≥27

vs

<27

μg/

m3 ):

A

djus

ted

for

mat

chin

g va

riabl

es: 0

.98

(0.6

6, 1

.45)

F

urth

er a

djus

ted

mod

el:

1.05

(0.

65, 1

.69)

F

urth

er a

djus

ted

for

cotin

ine

: 2.

85 (

0.97

, 8.3

3)

Fur

ther

ad

just

ed

for

occu

patio

nal i

ndex

: 1.

02 (

0.68

, 1.5

1).

report no. 4/11

167

EUR

OPE

AN

EC

OLO

GIC

ST

UD

Y

Na

wro

t et

al

., 20

07

(Naw

rot e

t al,

2007

) E

colo

gica

l st

udy;

15

E

urop

ean

cou

ntrie

s.

Ann

ual

me

an

PM

2.5;

es

timat

ed

for

the

year

20

02)

betw

een

1

(Fin

land

) an

d 22

(B

elgi

um).

Thi

s ec

olog

ical

st

udy

ana

lyze

d th

e re

latio

n be

twee

n ag

e an

d sm

okin

g lu

ng c

ance

r ra

tes

in

men

ac

ross

15

E

urop

ean

co

untr

ies

(obt

aine

d fr

om

the

EU

CA

N

data

base

fo

r th

e199

8),

and

annu

al m

ean

PM

2.5

conc

entr

atio

ns e

stim

ated

for

th

e ye

ar 2

002.

A

sign

ifica

nt

corr

elat

ion

betw

een

coun

trie

s’ag

e

and

smok

ing

stan

dard

ized

m

orta

lity

rate

s fo

r lu

ng c

ance

r in

men

and

an

nual

mea

n P

M2.

5 w

as

show

n (

Spe

arm

an

corr

elat

ion

coef

ficie

nt,

r=0.

57;

p=0.

03).

No

rela

tion

was

ev

iden

t fo

r w

omen

(r

=0.

37;

p=0.

18).

Aut

hor

s co

nclu

ded

sug

gest

ing

that

so

me

of

the

diffe

renc

es

in

lung

ca

ncer

m

orta

lity

in E

urop

e co

uld

be e

xpla

ined

by

fine

part

icul

ate

air

conc

entr

atio

n.

RR

for

an

incr

emen

t of

5 μ

g/m

3

of

PM

2.5

in

men

: 1.

18

(1.0

4,

1.32

).

Subn

atio

nal s

tudi

es

G

REA

T B

RIT

AIN

Kno

x, 2

005

(Kno

x, 2

005)

P

opul

atio

n:

All

child

ren

dy

ing

for

leuk

aem

ia

or

othe

r ca

ncer

s be

twee

n

1955

and

19

80 i

n G

reat

B

ritai

n.

Mea

n va

lue

of

PM

w

as

not g

iven

.

In

this

st

udy,

bi

rth

and

deat

h ad

dres

ses

of

child

ren

(age

d <

16

year

s) d

ying

fro

m c

ance

r be

twee

n 19

55

and

1980

in

Gre

at B

ritai

n w

ere

linke

d to

e

mis

sion

ho

tspo

ts

for

spec

ific

chem

ical

s, i

ncl

udin

g P

M10

, C

O,

NO

x, o

btai

ned

for

the

year

200

1. A

mon

g ch

ildre

n w

ho m

oved

ho

use,

di

stan

ces

from

ea

ch

addr

ess

to

the

near

est

haza

rd w

ere

com

pare

d. T

he a

im o

f th

is

stud

y w

as

to e

xam

ine

the

exc

ess

es o

f cl

ose-

to-

haza

rd b

irth

addr

esse

s co

mpa

red

with

clo

se t

o ha

zard

dea

th a

ddre

sses

, in

ord

er t

o un

ders

tand

w

heth

er p

rena

tal

or e

arly

pos

tnat

al e

xpo

sure

to

oil

com

bust

ion

gase

s in

itiat

es

canc

ers.

E

stim

ates

of

R

R

wer

e b

ased

on

bi

rth/

deat

h ra

tios

for

child

ren

who

m

ove

d ho

uses

w

ithin

va

rious

di

stan

ces.

A

tmos

pher

ic

emis

sion

s ho

tspo

ts

we

re

conv

erte

d to

co

ordi

nate

s.

Dis

tanc

es

to

indu

stria

l si

tes,

in

clud

ing

bu

s st

atio

n,

railw

ays

, ho

spita

ls,

inci

nera

tors

, m

otor

way

s w

ere

als

o co

nsid

ered

.

The

re

wer

e ex

cess

R

R

with

in

1 km

of

ho

tspo

ts f

or P

M10

, C

O,

NO

x, a

nd o

ther

oil

base

d co

mbu

stio

n ga

ses

(par

ticul

arly

1,3

-bu

tadi

ene)

, an

d w

ithin

1.

0 km

of

bu

s st

atio

ns,

hosp

itals

, he

avy

tran

spor

t ce

ntre

s,

railw

ays,

and

oil

inst

alla

tion

s.

The

au

thor

co

nclu

ded

th

at

child

hood

ca

ncer

s w

ere

stro

ngly

de

term

ined

by

pr

enat

al o

r ea

rly p

ostn

atal

exp

osu

res

to o

il ba

sed

com

bust

ion

gase

s,

espe

cial

ly

fro

m

engi

ne e

xhau

st.

Am

ong

child

ren

who

m

ove

d ho

use,

di

stan

ces

with

in

1

km

from

ea

ch

addr

ess

to

the

near

est

emis

sion

of

P

M10

ho

tspo

t: B

irths

= 1

,420

; D

eath

s=77

7

RR

=1.

83 (

1.6

7, 2

.00)

.

report no. 4/11

168

Kno

x, 2

006

(Kno

x, 2

006)

S

ame

stud

y de

sign

as

K

nox,

200

5 (K

nox,

200

5).

Thi

s is

a r

e-an

alys

is o

f th

e p

revi

ous

stu

dy f

or

indu

stria

l si

tes

and

road

s,

cons

ider

ing

mor

e pr

ecis

e an

d ad

equa

te d

ata

on r

oads

, ra

il an

d in

dust

rial s

ites.

Sig

nific

ant

birt

h ex

cess

es w

ere

foun

d w

ithin

sh

ort

dist

ance

s of

bu

s st

atio

ns,

railw

ay

stat

ions

, fe

rrie

s,

railw

ays,

an

d A

, B

cl

ass

ro

ads.

As

in t

he p

revi

ous

stud

y, t

he a

uth

or

conc

lude

d th

at

child

ca

ncer

ini

tiatio

ns w

ere

st

rong

ly

dete

rmin

ed

by

pren

atal

or

ea

rly

post

nata

l e

xpos

ures

to

en

gine

e

xha

ust

gase

s

No

estim

ates

for

PM

.

NO

RW

AY

N

afst

ad

et

al.,

2003

(N

afst

ad

et

al,

2003

);

Naf

stad

et

al

., 20

04

(Naf

stad

et a

l, 20

04)

Coh

ort

of

16,

209

men

fr

om

Osl

o,

Nor

way

, fo

llow

-up

perio

d: 1

972/

73

to 1

998.

N

o in

form

atio

n on

PM

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

long

ter

m e

xpos

ure

to S

O2 a

nd N

Ox

and

lung

ca

ncer

in

cide

nce

in

a co

hort

of

O

slo

men

fo

llow

ed f

or 2

7 ye

ars.

Co

x pr

opor

tiona

l h

azar

ds

regr

essi

on

afte

r ad

just

men

t fo

r sm

okin

g,

educ

atio

n a

nd

age.

A

n

addi

tiona

l m

odel

in

clud

ed th

e tw

o co

-pol

luta

nts

.

Dur

ing

the

follo

w-u

p pe

riod,

lu

ng

canc

er

occu

rred

in 4

18

men

. T

he a

djus

ted

RR

for

a

10

mg/

m3

incr

ease

in

av

erag

e ho

me

addr

ess

expo

sure

bet

we

en 1

974

and

1978

w

as

1.08

(95

% C

I: 1

.02-

1.15

) fo

r N

Ox

and

1.

01 (

95%

CI:

0.94

-1.0

8) fo

r S

O2.

No

estim

ates

for

PM

.

Nae

ss e

t al

., 20

07 (

Nae

ss

et a

l, 20

07)

Coh

ort

of

all

inha

bita

nts

of O

slo

(143

,842

).

Fol

low

-up

perio

d:

1992

-19

98.

PM

2.5

rang

e: 6

.56-

22.3

4 P

M10

ran

ge: 6

.57-

30.1

3

Thi

s st

udy

inve

stig

ated

the

ass

ocia

tion

betw

een

conc

entr

atio

ns

of P

M10

, P

M2.

5 an

d N

O2

in 1

992-

1995

, an

d ca

use-

spec

ific

mor

talit

y,

incl

udin

g lu

ng

canc

er.

The

po

pula

tion

incl

ude

d al

l in

habi

tant

s of

Osl

o N

orw

ay,

aged

51–

90 y

ears

on

Jan

uary

199

2 w

ith f

ollo

w-u

p of

dea

ths

from

19

92 t

o 19

98.

An

air

disp

ersi

on m

odel

was

use

d to

es

timat

e le

vels

of

e

xpos

ure

in

all

470

ad

min

istr

ativ

e ne

ighb

ourh

oods

. C

ox

prop

ortio

nal

haza

rds

regr

essi

on

mod

els

wer

e u

sed

afte

r ad

just

men

t fo

r ag

e, e

duca

tion

and

occu

patio

nal

clas

s. T

o m

odel

the

rel

atio

n be

twee

n ai

r po

lluta

nts

and

mor

talit

y,

GA

M

mod

els

wer

e us

ed.

Dur

ing

follo

w-u

p, 1

,453

lun

g ca

ncer

dea

ths

occu

rred

. S

om

e di

rect

as

soci

atio

ns

we

re

obse

rved

be

twee

n P

M

and

lu

ng

can

cer

mor

talit

y.

The

ef

fect

s w

ere

sm

all

in

the

youn

g ag

e gr

oup

(51-

70 y

ears

) of

men

and

m

oder

ate

to l

arge

in

the

old

age

grou

p (7

1-90

ye

ars)

. W

omen

ha

d pa

rtic

ular

ly

larg

e ef

fect

s in

th

e yo

ung

gro

up.

The

th

ree

pollu

tant

s sh

are

d si

mila

r re

sults

, be

ing

the

ir co

rrel

atio

ns h

igh

(bet

wee

n 0

.88

and

0.95

).

Occ

upat

iona

l cl

ass

and

educ

atio

n ad

just

ed

HR

fo

r qu

artil

e in

crea

se o

f exp

osur

e:

PM

2.5

Men

51

-70

year

s:

1.07

(0

.97-

1.18

) W

omen

51

-70

year

s:

1.27

(1

.13-

1.43

) M

en

71-9

0 ye

ars:

1.

07

(0.9

7-1.

18)

Wom

en

71-9

0 ye

ars:

1.

16

(1.0

2-1.

32)

PM

10

Men

51

-70

year

s:

1.07

(0

.97-

1.18

) W

omen

51

-70

year

s:

1.27

(1

.13-

1.43

) M

en

71-9

0 ye

ars:

1.

08

(0.9

8-1.

18)

Wom

en

71-9

0 ye

ars:

1.

17

(1.0

3-1.

33).

report no. 4/11

169

SWED

EN

N

yber

g et

al

. (2

000)

(N

yber

g et

al,

2000

).

Cas

e-co

ntro

l st

udy

on

1,04

2 ca

ses

died

for

lun

g ca

ncer

and

2,3

64 c

ontr

ols

died

for

oth

er d

isea

ses

in

Sto

ckho

lm.

Stu

dy p

erio

d 1

985-

1990

. N

o in

form

atio

n on

PM

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

expo

sure

to

NO

x/N

O2

and

SO

2 an

d lu

ng c

ance

r m

orta

lity

in a

cas

e-co

ntro

l stu

dy b

ased

on

1,0

99

case

s di

ed f

or l

ung

canc

er a

nd t

wo

com

pan

ion

grou

ps (

1,27

5 al

ive

cont

rols

and

1,0

90 m

atch

ed

cont

rols

di

ed

for

othe

r d

isea

ses)

. Lo

cal

air

pollu

tion

leve

ls w

ere

estim

ated

usi

ng v

alid

ated

di

sper

sion

mod

els.

OR

s w

ere

deriv

ed b

y lo

gist

ic

regr

essi

on

mod

els

afte

r ad

just

men

t fo

r ag

e,

smok

ing,

exp

osur

e to

occ

upat

iona

l ca

rcin

ogen

s an

d so

cioe

cono

mic

gro

up (

data

obt

aine

d fr

om

each

sub

ject

’s n

ext o

f kin

).

NO

2 e

xpo

sure

ov

er

30

year

s w

as

not

si

gnifi

cant

ly

asso

ciat

ed

to

lung

ca

nce

r m

orta

lity

(OR

for

an

incr

emen

t by

10 μg

/m3

wa

s 1.

05

(95%

C

I: 0.

93,

1.18

).

Whe

n co

nsid

erin

g N

O2

exp

osu

re

20

year

s pr

evio

usly

, a

bord

erlin

e si

gnifi

cant

di

rect

as

soci

atio

n w

as f

ound

with

NO

2 (O

R=

1.10

; 95

%

CI

0.97

, 1.

23)

No

asso

ciat

ion

wa

s ob

serv

ed w

ith S

O2.

No

estim

ates

for

PM

.

DEN

MA

RK

Raa

scho

u-N

iels

en

et

al.

(200

1)

(Raa

scho

u-N

iels

en

et

al,

2001

);

Raa

scho

u-N

iels

en

et

al.

(200

2)

(Raa

scho

u-N

iels

en e

t al,

2002

).

Cas

e-co

ntro

l st

udy

on

1,98

9 ch

ildre

n c

ases

and

5,

506

cont

rols

, D

enm

ark,

19

68-1

991.

N

o in

form

atio

n on

PM

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

traf

fic-r

elat

ed a

ir po

llutio

n a

nd t

he r

isk

of c

ance

r du

ring

child

hood

. D

urin

g 19

68-1

991,

the

Dan

ish

Can

cer

Reg

istr

y re

port

ed 1

,989

chi

ldre

n w

ith a

di

agno

sis

of

leuk

emia

, ca

ncer

of

th

e ce

ntra

l ne

rvou

s sy

ste

m,

or m

alig

nant

lym

phom

a. T

hese

ch

ildre

n w

ere

com

pare

d

with

5,

506

co

ntro

l ch

ildre

n ra

ndom

ly

sele

cte

d fr

om

the

entir

e ch

ildho

od p

opul

atio

n. T

he r

esid

entia

l his

tori

es o

f th

e ch

ildre

n w

ere

trac

ed f

rom

9 m

onth

s be

fore

bi

rth

until

the

tim

e of

dia

gno

sis

of t

he c

ases

and

a

sim

ilar

perio

d fo

r th

e co

ntro

ls.

For

eac

h of

the

18

,440

id

entif

ied

addr

esse

s,

info

rmat

ion

on

traf

fic

and

the

conf

igur

atio

n of

st

reet

s an

d bu

ildin

gs w

as c

olle

cted

. A

vera

ge c

once

ntra

tions

of

ben

zene

an

d N

O2

(indi

cato

rs o

f tr

affic

-rel

ated

ai

r po

llutio

n)

wer

e

calc

ulat

ed

for

the

rele

vant

pe

riod,

an

d ex

posu

res

to

air

pollu

tion

durin

g pr

egna

ncy

and

durin

g ch

ildho

od

wer

e ca

lcul

ated

sep

arat

ely.

The

ris

ks

of

leuk

emia

, ce

ntra

l ne

rvou

s sy

stem

tu

mor

s,

and

all

sele

cted

ca

ncer

s co

mbi

ned

we

re n

ot l

inke

d to

exp

osur

e t

o be

nzen

e or

N

O2.

T

he

risk

of

lym

pho

mas

in

crea

sed

by 2

5% (

p f

or t

rend

= 0

.06)

and

51

% (

p fo

r tr

end

= 0

.05)

for

a d

oubl

ing

of

the

conc

entr

atio

n of

ben

zene

and

nitr

ogen

di

oxid

e, r

espe

ctiv

ely,

dur

ing

the

pre

gnan

cy.

The

ass

ocia

tion

was

res

tric

ted

to H

odgk

in's

di

seas

e.

No

estim

ates

for

PM

.

report no. 4/11

170

THE

NET

HER

LAN

DS

H

oek

et a

l. (2

002)

(H

oek

et a

l, 20

02)

The

Net

herla

nds

Coh

ort s

tudy

19

86-1

994

Sub

ject

s= 4

,492

; B

S e

xpos

ure,

mea

n (S

D):

ba

ckgr

ound

15

.1

(2.5

);

back

grou

nd

and

loca

l 15

.5 (

3.2)

.

This

stud

y ex

amin

ed th

e as

soci

atio

n be

twee

n B

S an

d N

O2 i

n a

coho

rt of

4,4

92 re

side

nts i

n va

rious

are

as o

f th

e N

ethe

rland

s and

cau

se-s

peci

fic m

orta

lity,

in

clud

ing

lung

can

cer.

Lo

ng-t

erm

ex

posu

re

to

tra

ffic-

rela

ted

BS

an

d

NO

2 w

as e

stim

ated

for

the

198

6 ho

me

addr

ess.

C

ox’

s pr

opor

tiona

l ha

zard

s m

odel

s w

ere

used

af

ter

adju

stm

ent

for

age,

sex

, ed

ucat

ion,

BM

I, oc

cupa

tion,

ac

tive

and

pa

ssiv

e ci

gare

tte

smok

ing,

an

d ne

ighb

ourh

ood

soci

oeco

nom

ic

scor

e.

Tw

o m

odel

s of

ex

posu

re

for

ever

y po

lluta

nt

we

re

used

: 1)

th

e ba

ckgr

ound

co

ncen

trat

ion

wa

s en

tere

d in

the

mod

el w

ith t

he

indi

cato

r va

riabl

e fo

r liv

ing

near

a m

ajor

roa

d. 2

) th

e su

m o

f th

e ba

ckgr

ound

and

the

est

imat

ed

cont

ribut

ion

from

liv

ing

near

a m

ajor

roa

d to

air

pollu

tion

conc

entr

atio

ns.

Too

few

peo

ple

die

d fr

om l

ung

canc

er t

o ob

tain

sta

ble

estim

ates

for

th

e in

dica

tor

varia

ble

for

livin

g ne

ar

a m

ajor

ro

ad.

Ove

rall,

60

lu

ng

canc

er

deat

hs

occu

rred

du

ring

the

follo

w-u

p pe

riod

. N

o si

gnifi

cant

as

soci

atio

n e

mer

ged

betw

een

bot

h B

S a

nd

NO

2 an

d lu

ng c

ance

r m

orta

lity.

RR

fo

r an

in

crem

ent

of

10

μg/m

3 (95

th –

5th p

erce

ntile

) of

B

S.

Bac

kgro

und

and

loca

l: 1.

06

(0.4

3, 2

.63)

.

Vis

ser

et a

l., 2

004

(Vis

ser

et a

l, 20

04)

Eco

logi

c st

udy

Am

ster

dam

, 198

9-19

97;

27,1

57 c

ance

r ca

ses.

N

o in

form

atio

n on

PM

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

resi

dent

ial t

raffi

c in

tens

ity,

and

can

cer

inci

denc

e in

A

mst

erda

m

in

1989

–199

7.

Dai

ly

traf

fic

inte

nsity

dat

a f

or i

ndiv

idua

l ad

dres

ses

alo

ng t

he

mai

n ro

ads

wer

e lin

ked

with

th

e po

pula

tion-

base

d re

gion

al c

ance

r re

gist

ry.

SIR

w

ere

der

ived

by

co

mpa

rison

b

etw

een

ob

serv

ed n

umbe

rs o

f ca

ncer

for

res

iden

ts a

long

m

ain

road

s w

ith

expe

cte

d nu

mbe

rs

deriv

ed

usin

g th

e ag

e gr

oup-

and

sex

-sp

ecifi

c ca

ncer

in

cide

nce

in t

he p

opul

atio

n n

ot r

esid

ing

alon

g th

e m

ain

road

s.

Ana

lysi

ng

27,1

57 c

ases

, n

o cl

ear

evid

enc

e of

an

asso

ciat

ion

betw

een

resi

denc

e al

ong

mai

n ro

ads

and

the

inci

denc

e of

can

cer

in

adul

ts e

mer

ged

(SIR

=1.

03;

95%

CI:

1.00

-1.

07),

alth

ough

for

sub

ject

s re

side

nts

alon

g th

e m

ain

road

s an

e

xce

ss

risk

of

hem

atol

ogic

al

mal

igna

ncie

s in

fe

mal

es

(SIR

=1.

23;

95

% C

I: 1.

04-

1.44

) an

d ch

ildre

n (S

IR f

or a

cute

lym

phoc

ytic

leu

kaem

ia =

2.5;

95

%

CI:

0.8

-5.9

) w

as

foun

d.

Mor

eove

r,

resi

dent

ial t

raffi

c in

tens

ity i

ncr

ease

d th

e ris

k of

ga

stro

inte

stin

al

canc

er

in

mal

es

(SIR

=1.

16; 9

5C

I: 1.

04-1

.28)

.

No

estim

ates

for

PM

.

report no. 4/11

171

Vis

ser

et a

l., 2

005

(Vis

ser

et a

l, 20

05)

Eco

logi

c st

udy

Sch

ipho

l, A

mst

erda

m,

1988

-200

3;

13,2

07 c

ance

r ca

ses.

P

M10

(20

02),

mea

n: 4

0.

Thi

s st

udy

inve

stig

ated

th

e in

cide

nce

of

lu

ng

canc

er b

etw

een

198

8 an

d 20

03 f

or r

esid

ents

of

the

Am

ster

dam

A

irpor

t S

chip

hol,

whe

re

elev

ated

co

ncen

trat

ions

of

po

tent

ial

carc

inog

enic

co

mpo

unds

, in

clud

ing

ben

zene

, P

M10

, C

O

and

SO

2,

wer

e

obse

rved

. C

ance

r ag

e-st

anda

rdiz

ed

inci

denc

e ra

tio

(SIR

) w

ere

com

pute

d us

ing

natio

nal

inci

denc

e ra

tes

as a

re

fere

nce.

Ana

lysi

ng

13,2

07 c

ases

, n

o cl

ear

evid

enc

e of

an

asso

ciat

ion

betw

een

resi

denc

e ar

ound

S

chip

hol

area

and

the

in

cid

ence

of

canc

er

in a

dults

em

erge

d (S

IR=

1.0

2; 9

5% C

I: 1.

00,

1.03

),

a w

here

as

stat

istic

ally

si

gnifi

can

tly

incr

ease

d in

cide

nce

wer

e fo

und

for

hem

atol

ogic

al

mal

igna

ncie

s (S

IR=

1.1

2;

95%

CI:

1.05

, 1.

19),

the

inc

iden

ce o

f ca

ncer

of

th

e re

spira

tory

sy

stem

w

as

stat

istic

ally

si

gnifi

cant

ly d

ecre

ased

(S

IR=

0.94

, 95

% C

I: 0.

90,

0.99

), b

ecau

se o

f to

the

lo

w r

ate

in

mal

es (

SIR

0.8

9).

No

estim

ates

for

PM

.

FRA

NC

E

Fill

eul e

t al

. (2

005)

(F

illeu

l et

al,

2005

) P

AA

RC

sur

vey

24

area

s of

7

Fre

nch

citie

s pe

riod

of e

xpos

ure

mea

sure

men

t: 19

74-1

976

Sub

ject

s= 1

4,28

4 ad

ults

T

SP

min

/ma

x: 4

5/24

3 B

S m

in/m

ax:

18/

152.

Thi

s st

udy

exam

ined

the

lon

g te

rm e

ffect

s of

T

SP

, B

S,

SO

2,

NO

2 an

d N

O (

daily

ass

esse

d in

19

74-1

976)

on

mor

talit

y, i

nclu

ding

lun

g ca

ncer

m

orta

lity

in

the

Pol

lutio

n

Atm

osph

eriq

ue

et

Affe

ctio

ns

Re

spira

toire

s C

hron

ique

s (P

AA

RC

) su

rvey

, co

nduc

ted

in 2

4 ar

eas

of 7

Fre

nch

citie

s on

14,

284

adul

ts,

follo

wed

for

the

per

iod

1974

-20

01.

RR

s w

ere

estim

ated

by

Co

x pr

opor

tiona

l ha

zard

reg

ress

ion

mod

els,

afte

r ad

just

men

t fo

r ag

e,

sex,

sm

okin

g,

BM

I,

educ

atio

n,

and

occu

patio

nal

expo

sure

. T

he

anal

yses

w

ere

pe

rfor

med

for

all

24 a

reas

and

in

a su

bgro

up o

f 18

ar

eas

with

a

ratio

of

N

O/

NO

2 <

3

(with

m

onito

rs p

oten

tially

influ

ence

d by

loca

l tra

ffic)

.

Afte

r ap

prox

imat

ely

25 y

ears

of

follo

w-u

p,

178

lung

ca

ncer

de

aths

oc

curr

ed.

Con

side

ring

all

the

24

are

as,

and

afte

r ex

clus

ion

of

6 ar

eas

influ

ence

d by

lo

cal

traf

fic,

no a

ssoc

iatio

n w

as

foun

d be

twe

en

TS

P,

BS

an

d th

e ot

her

cons

ider

ed

co-

pollu

tant

s, a

nd

lung

can

cer

mor

talit

y. N

O2

sign

ifica

ntly

in

crea

sed

the

mor

talit

y fo

r lu

ng

canc

er.

Mor

talit

y R

R f

or a

n in

crem

ent

of

10 μ

g/m

3 of T

SP

: 24

are

as: 0

.97

(0.9

4-1.

01)

18 a

reas

not

influ

ence

d by

loca

l tr

affic

: 1.0

0 (0

.92-

1.10

) M

orta

lity

RR

for

an

incr

eme

nt o

f 10

μg/

m3 o

f BS

: 24

are

as: 0

.97

(0.9

3-1.

01)

18 a

reas

not

influ

ence

d by

loca

l tr

affic

: 1.0

3 (0

.92-

1.15

).

ITA

LY

P

arod

i et

al

. (2

005)

(P

arod

i et a

l, 20

05).

C

orni

glia

no,

a di

stric

t of

th

e G

enoa

m

unic

ipal

ity,

nort

hern

Ital

y, 1

986-

1997

. P

M10

, an

nua

l m

ean

be

twee

n 57

an

d 79

be

fore

th

e co

ke

oven

cl

osin

g (2

001

) an

d 43

in

20

02.

Thi

s st

udy

inve

stig

ated

th

e in

cide

nce

of

lu

ng

canc

er b

etw

een

198

6 an

d 19

97 f

or r

esid

ents

of

an a

rea

of n

orth

ern

Italy

nea

r a

coke

ove

n p

lant

, w

here

el

evat

ed

conc

entr

atio

ns

of

pote

ntia

l ca

rcin

ogen

ic

com

poun

ds,

incl

udin

g be

nze

ne,

PM

10,

CO

an

d S

O2,

wer

e ob

serv

ed a

roun

d th

e co

ke

oven

. A

ge-s

tand

ardi

zed

inci

denc

e

ratio

s (S

IR)

betw

een

Cor

nigl

iano

an

d tw

o

sele

cted

re

fere

nce

popu

latio

ns

(Riv

arol

o an

d G

enoa

) w

ere

deriv

ed.

In

Cor

nigl

ian

o,

158

lung

ca

ncer

ca

ses

occu

rred

in

men

, an

d 28

in

wom

en.

Onl

y a

mar

gina

l e

xces

s ris

k of

lu

ng

canc

er

wa

s ob

serv

ed

com

pare

d w

ith

two

sele

cted

co

ntro

l po

pula

tions

whi

le a

gra

dien

t in

the

ar

eas

clos

e to

th

e pl

ant

em

erge

d am

ong

fem

ales

. U

sing

G

enoa

a

s th

e re

fere

nce

popu

latio

n,

the

age-

adju

sted

S

IR

for

Cor

nigl

iano

was

1.1

9 (9

5% C

I: 1.

01-1

.38)

in

men

, an

d 0.

98

(95%

C

I: 0.

65-1

.41)

in

w

omen

.

No

estim

ates

for

PM

.

report no. 4/11

172

Bar

bone

et

al

. (1

995)

(B

arbo

ne e

t al,

1995

).

Cas

e-co

ntro

l st

udy

on

755

case

s di

ed

for

lung

ca

ncer

and

755

mat

ched

co

ntro

ls

died

fo

r ot

her

dise

ases

in T

riest

e.

Stu

dy

perio

d

1979

-198

1 an

d 19

85-1

986.

M

ean

tota

l pa

rtic

ulat

e

depo

sitio

n be

twee

n 0.

210

(rur

al

area

) an

d 0.

721

g/m

2 /day

(in

dust

rial a

rea)

.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

part

icul

ate

depo

sitio

n an

d l

ung

canc

er m

orta

lity

in a

cas

e-co

ntro

l stu

dy b

ase

d on

755

cas

es

died

fo

r lu

ng c

ance

r an

d 75

5 m

atch

ed c

ontr

ols

died

fo

r ot

her

dise

ases

in T

riest

e fr

om 1

976

to 1

981,

an

d fr

om

1985

to

19

86.

Air

pollu

tion

at

the

resi

denc

e of

eac

h su

bjec

t w

as

estim

ate

d fr

om

the

aver

age

valu

e of

par

ticul

ate

depo

sitio

n at

th

e ne

ares

t of

28

mon

itorin

g s

tatio

ns.

OR

s w

ere

de

rived

by

lo

gist

ic

regr

essi

on

mod

els

afte

r ad

just

men

t fo

r ag

e, s

mok

ing

habi

t, ex

posu

re t

o oc

cupa

tiona

l car

cino

gens

and

soc

ial c

lass

(da

ta

obta

ined

from

eac

h su

bjec

t’s n

ext o

f kin

).

The

ris

k of

lu

ng

canc

er

incr

ease

d w

ith

incr

easi

ng l

evel

of

air

pollu

tion

for

all

type

s of

lu

ng

canc

er

com

bine

d (p

pe

r tr

end=

0.02

2),

for

smal

l ce

ll ca

rcin

oma

(p=

0.01

6)

and

for

larg

e ce

ll ca

rcin

oma

(p=

0.04

9).

OR

fo

r to

tal

part

icul

ate

de

posi

tion>

0.29

8 vs

<

0.17

5

g/m

2 /day

: A

ll lu

ng c

ance

rs: 1

.4 (

1.1,

1.8

) S

quam

ous:

1.2

(0.

8, 1

.7)

Sm

all c

ell:

1.7

(1.

1, 2

.5)

Larg

e ce

ll: 1

.7 (

0.9,

3.0

) A

deno

carc

ino

ma:

1.3

(0.

8, 2

.0).

Cro

sign

ani

et

al.

(200

4)

(Cro

sign

ani e

t al

, 200

4).

Cas

e-co

ntro

l st

udy

(120

ca

ses

with

ch

ildho

od

leuk

aem

ia,

and

480

cont

rols

),

Var

ese,

no

rthe

rn It

aly,

197

8-19

97.

No

info

rmat

ion

on P

M.

Thi

s st

udy

exam

ined

the

effe

ct o

f an

nual

mea

n co

ncen

trat

ion

of

be

nzen

e on

th

e

risk

of

child

hood

le

uke

mia

, us

ing

a po

pula

tion-

base

d ca

se-

cont

rol

stud

y in

th

e P

rovi

nce

of V

ares

e,

nort

hern

Ital

y. A

ll 1

20 in

cide

nt c

ases

from

197

8–97

wer

e in

clu

ded

in t

he s

tudy

. C

ontr

ols

wer

e 48

0 se

x-

and

ag

e-m

atch

ed

child

ren

sam

pled

fr

om t

he g

ener

al p

opul

atio

n. T

he c

once

ntra

tion

of

be

nzen

e w

as

mea

sure

d ou

tsid

e th

e

hom

e us

ing

a G

auss

ian

diffu

sion

m

odel

. O

Rs

wer

e de

rived

by

lo

gist

ic

regr

essi

on

cond

ition

ed

by

age

and

sex.

Com

pare

d to

ch

ildre

n w

hos

e ho

mes

w

as

not

expo

sed

to r

oad

traf

fic e

mis

sion

s (<

0.1

μg

/m3 o

f be

nzen

e an

nual

ave

rage

), t

he r

isk

of

child

hood

le

ukae

mia

w

as

sign

ifica

ntly

hi

gher

fo

r he

avily

e

xpos

ed

child

ren

(>10

μg

/m3 ),

the

RR

bei

ng 3

.91

(95%

CI:

1.36

, 11

.27)

.

No

estim

ates

for

PM

.

POLA

ND

Jedr

ycho

wsk

i et

al

. (1

990)

(J

edry

cho

wsk

i et

al

, 199

0)

Cas

e-co

ntro

l st

udy

on

1,09

9 ca

ses

died

for

lun

g ca

ncer

and

1,0

73 c

ontr

ols

freq

uenc

y m

atch

ed

by

age

and

sex

died

fo

r ot

her

dise

ase

s in

Cra

cow

. S

tudy

per

iod

198

0-19

85.

Mea

n T

SP

not

pro

vide

d.

Thi

s st

udy

exa

min

ed t

he a

ssoc

iatio

n b

etw

een

expo

sure

to

ai

r po

llutio

n an

d lu

ng

canc

er

mor

talit

y in

a c

ase-

cont

rol s

tudy

bas

ed o

n 1

,099

ca

ses

died

for

lun

g ca

ncer

and

1,0

73 m

atch

ed

cont

rols

di

ed

for

othe

r di

seas

es

in

Cra

cow

, P

olan

d be

twe

en 1

980

and

1985

. A

ir po

llutio

n at

th

e re

side

nce

of e

ach

subj

ect

wa

s de

fined

on

the

basi

s of

th

e co

mbi

ned

conc

entr

atio

n o

f T

SP

an

d S

O2,

det

erm

ined

by

20 m

onito

ring

stat

ions

fo

r 8

year

s (1

973-

1980

). O

Rs

wer

e d

eriv

ed b

y lo

gist

ic r

egre

ssio

n m

odel

s af

ter

adju

stm

ent

for

age,

sm

okin

g h

abit,

exp

osur

e to

occ

upat

iona

l ca

rcin

ogen

s a

nd e

duca

tion

(da

ta o

btai

ned

from

ea

ch s

ubje

ct’s

nex

t of k

in).

The

ris

k of

lu

ng

canc

er

incr

ease

d w

ith

incr

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115. Ross Anderson H, Atkinson R, Peacock J, Marston L, Konstantinou K (2004) Meta-analysis of time-series studies ad panel studies of Particulate Matter (PM) and

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143. Visser O, van Wijnen JH, van Leeuwen FE (2004) Residential traffic density and cancer incidence in Amsterdam, 1989-1997. Cancer Causes Control 15: 331-339.

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145. von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D'Ippoliti D, Elosua R, Hormann A, Kulmala M, Lanki T, Lowel H, Pekkanen J, Picciotto S, Sunyer J, Forastiere F (2005) Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Circulation 112: 3073-3079.

146. Wheeler BW, Ben-Shlomo Y (2005) Environmental equity, air quality, socioeconomic status, and respiratory health: a linkage analysis of routine data from the Health Survey for England. J Epidemiol Community Health 59: 948-954.

147. Wichmann H-E, Spix C, Tuch T, Wolke G, Peters A, Heinrich J, Kreyling WG, Heyder J (2000) Daily mortality and fine and ultrafine particles in Erfurt, Germany. Part I: role of particle number and particle mass. Research Report no. 98. Health Effects Institute: Cambridge, MA.

148. Wichmann HE (2004) What can we learn today from the Central European smog episode of 1985 (and earlier episodes)? Int J Hyg Environ Health 207: 505-520.

149. Wolf C (2002) Urban air pollution and health: an ecological study of chronic rhinosinusitis in Cologne, Germany. Health Place 8: 129-139.

150. Wong CM, Atkinson RW, Anderson HR, Hedley AJ, Ma S, Chau PY, Lam TH (2002) A tale of two cities: effects of air pollution on hospital admissions in Hong Kong and London compared. Environ Health Perspect 110: 67-77.

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159. Zmirou D, Schwartz J, Saez M, Zanobetti A, Wojtyniak B, Touloumi G, Spix C, Ponce de Leon A, Le Moullec Y, Bacharova L, Schouten J, Ponka A, Katsouyanni K (1998) Time-series analysis of air pollution and cause-specific mortality. Epidemiology 9: 495-503.

report no. 4/11

186

APP

END

IX 1

.1 -

SHO

RT-

TER

M P

AR

TIC

ULA

TE M

ATT

ER (P

M) A

ND

MO

RTA

LITY

(DER

IVED

FR

OM

EPA

199

7).

Ref

eren

ce, L

ocat

ion,

Yea

rs, P

M In

dex,

M

ean

or M

edia

n (µ

g/m

3 ). St

udy

Des

crip

tion.

Mod

elin

g m

etho

ds: l

ags,

sm

ooth

ing,

co-

pollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

.

G

REA

T B

RIT

AIN

T

hurs

ton

et a

l., (

1989

) (T

hurs

ton

et a

l, 19

89)

B

S m

ean:

90.

1; 2

4-h

avg

. d

aily

max

: 709

. D

aily

tot

al m

orta

lity

ana

lyze

d fo

r as

soci

atio

ns w

ith B

S,

SO

2, a

nd H

2S

O4

in L

ond

on,

Eng

land

, du

ring

196

3 to

197

2 w

inte

rs. M

ean

dai

ly t

empe

ratu

re a

nd R

H a

lso

cons

ider

ed.

PM

, S

O2,

and

H2S

O4

all f

ound

to h

ave

sta

tistic

al

sign

ifica

nt a

ssoc

iatio

ns w

ith m

orta

lity

(0, 1

da

y la

g).

Tem

pera

ture

als

o co

rre

late

d (n

egat

ive

ly)

with

mor

talit

y,

but

with

2-d

ay

lag.

Se

ason

ality

add

ress

ed b

y st

udyi

ng

only

win

ters

and

by

appl

yin

g hi

gh-p

ass

filte

r to

the

se

ries

and

anal

yzin

g re

sidu

als.

Ito e

t al

., 1

993

(It

o et

al,

1993

) B

S m

ean:

90.

1; r

ang

e: 0

-350

. F

urth

er a

nal

ysis

of

Lond

on,

Eng

land

dat

a (

196

5 to

19

72)

ex

amin

ed b

y T

hurs

ton

et a

l. 19

89

(Thu

rsto

n et

al,

198

9).

Spe

ctra

l and

adv

ance

d tim

e se

ries

met

hods

use

d, e

.g.

pre

wh

iten

ing

and

aut

o-re

gres

sive

mov

ing

aver

age

m

etho

ds. V

aria

bles

con

sid

ered

incl

ude

d w

ere

BS

, SO

2,

H2S

O4,

tem

pera

ture

an

d R

H.

Est

imat

ed p

ollu

tion

mea

n e

ffec

t of

2 to

7%

of

all

Lon

don

win

ter

deat

hs (

mea

n =

281

/da

y),

but

vari

ous

pollu

tant

s’

effe

cts

not s

epar

ated

. In

depe

nden

t mod

el te

st o

n 1

962

epis

ode

con

firm

ed a

ppro

pria

ten

ess

of s

uch

met

hods

. Lo

ng-w

ave

add

ress

ed b

y co

nsid

erin

g w

inte

rs o

nly

and

b

y pr

ew

hite

nin

g th

e d

ata.

GER

MAN

Y

S

pix

et a

l. (1

993)

(S

pix

et a

l, 1

993)

T

SP

ran

ge: 1

0 to

650

.

Dai

ly t

ota

l mor

talit

y in

Erf

urt,

Eas

t Ger

man

y, d

urin

g 1

980

to 1

989

(m

edia

n =

6/d

ay)

rel

ated

to

SO

2, S

P, T

, RH

, and

pr

ecip

itatio

n. S

P o

nly

mea

sure

d in

198

8-1

989.

A

utor

egre

sssi

ve P

oiss

on m

ode

ls u

sed

(due

to

low

de

aths

/da

y) a

lso

incl

uded

indi

cato

r va

riabl

es f

or e

xtre

me

tem

pera

ture

an

d ad

just

men

ts f

or tr

end,

sea

son

, an

d in

flue

nza

ep

idem

ics.

Bot

h S

O2

and

SP

fou

nd to

be

sig

nific

antly

ass

ocia

ted

with

incr

ease

d m

orta

lity.

In

a si

mul

tane

ous

regr

essi

on,

S

P r

emai

ned

sig

nific

ant

wh

ile S

O2

did

not

. Cor

rela

tion

s of

thes

e co

effic

ient

s no

t pro

vide

d, h

ow

ever

. Pol

lutio

n ef

fect

siz

e si

mila

r to

that

for

met

eoro

log

y.

FR

AN

CE

Der

rien

nic

et a

l. (1

989

) (D

err

ienn

ic e

t al,

1989

) m

ean

TS

P (

OE

CD

Met

hod)

: L

yons

, Fra

nce:

87

(3 y

ear

) M

arse

illes

, Fra

nce:

126

(3

ye

ar).

Dai

ly t

ota

l, re

spira

tory

, an

d ca

rdia

c m

orta

lity

for

pers

ons

65 y

ears

of

age

test

ed

for

ass

ocia

tions

with

SO

2 an

d T

SP

du

ring

197

4 to

197

6 in

Lyo

ns a

nd M

arse

illes

, Fra

nce.

T

empe

ratu

re a

lso

cons

ider

ed in

ana

lyse

s.

No

sig

nific

ant m

orta

lity

asso

ciat

ions

fou

nd

with

TS

P,

but

S

O2

repo

rted

as

asso

ciat

ed w

ith to

tal e

lder

ly d

eath

s in

bo

th c

ities

. Se

ason

ality

ad

dre

ssed

by

anal

yzin

g de

viat

ions

fro

m 3

-ye

ar a

vera

ge o

f 31

-da

y ru

nni

ng

mea

ns o

f va

riabl

es, b

ut t

em

pera

ture

lags

not

con

side

red

and

prob

abl

e se

ason

al d

iffer

ence

s in

win

ter/

sum

mer

te

mpe

ratu

re-m

orta

lity

rela

tions

hip

not a

ddr

esse

d.

report no. 4/11

187

GR

EEC

E

K

atso

uya

nni e

t al

. 19

90a

(K

atso

uya

nni e

t al,

1990

a)

BS

.

Dai

ly t

ota

l mor

talit

y in

Ath

ens

, Gre

ece,

and

sur

rou

ndin

g bo

rou

ghs

(197

5 to

19

87)

rela

ted

to B

S,

SO

2, N

O2,

O3

, an

d C

O2

usin

g m

ultip

le r

egr

essi

on.

Dur

ing

win

ter

mon

ths

1983

to

1987

, th

e da

ily n

umbe

r of

de

aths

was

pos

itive

ly a

nd

stat

istic

ally

sig

nifi

cant

ly

asso

ciat

ed w

ith a

ll po

lluta

nts

, but

the

asso

ciat

ion

was

st

rong

est

with

BS

.

Kat

sou

yann

i et

al. 1

990

b (

Kat

sou

yann

i et a

l, 19

90b)

B

S a

nnua

l mea

n ra

nge:

51.

6 to

73.

3;

max

imum

dai

ly v

alue

: 79

0.

For

197

5 to

198

2 in

Ath

ens

, Gre

ece

199

da

ys w

ith h

igh

SO

2 (>

150

μg/m

3 ) ea

ch m

atch

ed o

n te

mp.

, ye

ar, s

easo

n,

day

of w

eek,

and

hol

ida

ys w

ith t

wo

low

SO

2 d

ays

. M

orta

lity

by-

caus

e co

mpa

red

bet

we

en g

roup

s b

y A

NO

VA

b

y ra

ndom

ize

d b

lock

s. B

S c

orre

late

d w

ith S

O2

at r

= 0

.73,

bu

t not

dire

ctly

use

d in

ana

lysi

s.

Mor

talit

y w

as g

ener

ally

hig

her

on h

igh

SO

2 d

ays

, w

ith

the

diff

eren

ce b

eing

mos

t pro

nou

nced

for

res

pira

tory

co

nditi

ons

. BS

leve

ls f

or e

ach

gro

up n

ot p

rovi

ded

, an

d B

S-S

O2

conf

oun

din

g n

ot a

ddr

esse

d, li

miti

ng

inte

rpre

tab

ility

of

resu

lts.

K

atso

uya

nni e

t al

. 19

93 (

Kat

sou

yan

ni e

t al,

1993

) B

S r

ang

e: 5

0 to

250

.

Dai

ly t

ota

l mor

talit

y in

Ath

ens

, Gre

ece,

dur

ing

July

, 19

87

(wh

en a

maj

or h

eat

wa

ve o

ccur

red)

com

pare

d to

dea

ths

in J

uly

for

pre

viou

s 6

yr.

Va

riabl

es c

onsi

dere

d in

clud

ed:

BS

, S

O2,

tem

pera

ture

, dis

com

fort

inde

x (D

I). E

ffec

ts o

f da

y-of

-wee

k, m

onth

, and

long

-ter

m tr

ends

add

ress

ed v

ia

dum

my

vari

able

s in

OL

S r

egr

essi

on m

odel

s.

Mea

n d

aily

tem

pera

ture

ab

ove

30

C f

ound

to

be

sign

ifica

ntly

ass

ocia

ted

with

mor

talit

y. T

he m

ain

effe

cts

of a

ll ai

r p

ollu

tant

s w

ere

non-

sign

ifica

nt, b

ut t

he

inte

ract

ion

betw

een

hig

h a

ir p

ollu

tion

and

tem

pera

ture

w

as s

ign

ifica

nt f

or S

O2

and

sugg

estiv

e (

p <

0.2

0) f

or O

3 an

d B

S.

T

oulo

umi e

t al.

(19

94)

(Tou

loum

i et a

l, 1

994)

B

S m

ean:

83;

ra

nge:

18

to 3

58.

Dai

ly t

ota

l mor

talit

y in

Ath

ens

, Gre

ece,

dur

ing

1984

-19

88

(mea

n =

38/

da

y) r

ela

ted

to B

S,

SO

2, C

O, T

, and

RH

. A

utor

egre

ssiv

e O

LS

mod

els

empl

oye

d al

so in

clud

ed

ind

icat

or v

aria

ble

s fo

r se

ason

, da

y of

wee

k, a

nd y

ear

.

BS

, S

O2,

and

CO

eac

h in

divi

dua

lly s

igni

fica

ntly

as

soci

ated

with

incr

ease

d m

orta

lity.

The

siz

e of

all

coef

ficie

nts

decl

ine

d in

sim

ulta

neo

us r

egre

ssio

ns,

with

S

O2

still

sig

nifi

cant

and

BS

app

roac

hin

g si

gni

fican

ce.

CO

was

no

long

er s

ign

ifica

nt, b

ut h

igh

ly c

orre

late

d w

ith

BS

(r

= 0

.74)

.

report no. 4/11

188

APP

END

IX 1

.2 -

SHO

RT-

TER

M P

AR

TIC

ULA

TE M

ATT

ER (P

M) A

ND

RES

PIR

ATO

RY

MO

RB

IDIT

Y.

Ref

eren

ce, L

ocat

ion,

Yea

rs, P

M In

dex,

M

ean

or M

edia

n (µ

g/m

3 ). St

udy

Des

crip

tion.

Mod

elin

g m

etho

ds: l

ags,

sm

ooth

ing,

co-

pollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

.

G

ERM

ANY

Sch

war

tz e

t al

., 1

991

(Sch

war

tz e

t al,

199

1)

Stu

dy

of a

cute

res

pira

tory

illn

ess

in c

hild

ren

in 5

Ger

man

com

mun

ities

, 19

83-1

985.

T

SP

med

ians

17

to 5

6.

Thi

s st

udy

exam

ined

the

impa

ct o

f sh

ort-

term

exp

osur

e to

ai

r po

llutio

n (T

SP

, S

O2

and

NO

2) o

n re

spira

tory

illn

ess

in

child

ren.

In

5 G

erm

an c

ities

dai

ly c

oun

ts o

f ch

ildre

n's

visi

ts

for

crou

p sy

mpt

oms

and

obst

ruct

ive

bron

chiti

s w

ere

reco

rded

. Dat

a w

ere

colle

cted

for

at l

east

2 y

ear

s in

ea

ch

loca

tion.

Au

tore

gres

sive

Po

isso

n re

gres

sio

n us

ing

GE

E

was

use

d. T

o fo

cus

the

ana

lysi

s on

sho

rt-t

erm

cor

rela

tions

an

d av

oid

sea

son

al c

onf

ound

ing,

bia

nnu

al, a

nnu

al

(sea

sona

l), a

nd s

ix s

hort

er t

erm

cyc

les

wer

e co

ntro

lled

for

in

the

reg

ress

ion

mod

els.

A to

tal o

f 6,

330

case

s of

cro

up a

nd 4

,755

cas

es o

f ob

stru

ctiv

e br

onch

itis

wer

e ob

serv

ed

dur

ing

the

stud

y.

Aft

er c

ontr

ollin

g fo

r sh

ort-

term

wea

ther

fac

tors

, TS

P

and

NO

2 w

ere

ass

ocia

ted

with

cro

up

case

s. A

n in

crea

se in

TS

P le

vels

fro

m 1

0 to

70

µg/

m3 w

as

asso

ciat

ed w

ith a

27%

incr

ease

in c

ases

of

crou

p; t

he

sam

e in

crea

se in

NO

2 le

vels

res

ulte

d in

a 2

8%

incr

ease

in c

ases

. No

pol

luta

nt w

as a

ssoc

iate

d w

ith

daily

cas

es o

f ob

stru

ctiv

e b

ronc

hitis

.

SP

AIN

S

unye

r et

al.

(19

93)

(Sun

yer e

t al,

1993

) A

dults

in B

arce

lona

, S

pai

n, 1

985-

198

9.

15 m

onito

ring

sta

tions

mea

surin

g B

S,

mea

n:

win

ter:

33%

tile

: 49

; 67

% t

ile =

77;

sum

mer

: 33

% t

ile =

36;

67%

tile

= 5

5.

In o

rder

to

exam

ine

the

asso

ciat

ion

betw

een

BS

and

SO

2 an

d th

e da

ily n

umbe

r of

em

erge

ncy

room

adm

issi

on in

B

arce

lona

, S

pain

, for

the

per

iod

198-

198

9, a

n au

tore

gres

sive

lin

ear

regr

ess

ion

anal

ysis

(0-

d la

g be

st)

afte

r ad

just

men

t for

tem

pera

ture

, da

y of

wee

k an

d ye

ar,

w

as u

sed.

An

incr

ease

of

25 µ

g/m

3 in S

O2

(24-

hou

r a

vera

ge)

prod

uce

d ad

just

ed

cha

nge

s of

6%

and

9%

in

emer

genc

y ro

om a

dmis

sion

s fo

r ch

roni

c ob

stru

ctiv

e

pulm

onar

y di

seas

e du

ring

win

ter

and

sum

mer

, re

spec

tivel

y. F

or B

S, a

sim

ilar

chan

ge w

as f

ound

du

ring

win

ter

(RR

for

50

µg

/m3 in

crea

se w

as 1

.15,

95

% C

I: 1

.09-

1.2

1), a

lthou

gh

the

cha

nge

was

sm

alle

r in

sum

mer

(R

R f

or 5

0 µ

g/m

3 incr

ease

was

1.0

5, 9

5%

CI:

0.98

-1.1

2). T

he a

ssoc

iatio

n o

f ea

ch p

ollu

tant

with

ch

roni

c o

bstr

uctiv

e p

ulm

onar

y d

isea

se a

dmis

sion

s re

mai

ned

sign

ifica

nt a

fter

con

trol

for

the

oth

er

pollu

tant

.

report no. 4/11

189

APP

END

IX 1

.3 -

LON

G-T

ERM

PA

RTI

CU

LATE

MA

TTER

(PM

) AN

D M

OR

TALI

TY.

Ref

eren

ce, L

ocat

ion,

Yea

rs, P

M In

dex,

M

ean

or M

edia

n (µ

g/m

3 ). St

udy

Des

crip

tion.

Mod

elin

g m

etho

ds: l

ags,

sm

ooth

ing,

co-

pollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

.

C

ZEC

H R

EPU

BLI

C

Bob

ak &

Leo

n, 1

992

(Bo

bak

andL

eon,

19

92)

Eco

logi

c st

ud

y, C

zech

Rep

ublic

, 19

86-1

988.

P

M1

0 m

ean:

68.

5.

An

eco

logi

cal s

tud

y of

neo

nat

al m

orta

lity

(age

s le

ss th

an

1 m

onth

) an

d po

st-n

eon

ata

l mor

talit

y (a

ges

1 t

o 1

2 m

onth

s)

and

air

pol

lutio

n w

as c

ondu

cted

in th

e C

zech

Rep

ubl

ic.

Dat

a on

infa

nt m

orta

lity

and

PM

10, S

O2

and

NO

x w

ere

colle

cted

in t

he p

erio

d 1

986

-88

for

46 o

f th

e 8

5 di

stric

ts in

th

e re

pub

lic. R

Rs

wer

e de

rive

d b

y lo

gist

ic r

egre

ssio

n m

odel

s ad

just

ed f

or d

istr

ict

soci

oeco

nom

ic c

hara

cter

istic

s,

such

as

inco

me,

car

ow

ners

hip,

and

abo

rtio

n ra

te.

A w

eak

pos

itive

ass

ocia

tion

bet

wee

n ne

ona

tal

mor

talit

y a

nd q

uint

ile o

f P

M10

and

SO

2 w

as f

ound

. S

tron

ger

adju

sted

eff

ects

wer

e se

en f

or p

ostn

eona

tal

mor

talit

y, w

ith a

con

sist

ent

incr

ease

in r

isk

for

incr

easi

ng q

uint

iles

of P

M10

(p <

0.0

01)

. Wea

ker

and

less

con

sist

ent e

vide

nce

of

a po

sitiv

e as

soci

atio

n w

ith

NO

x (p

= 0

.061

) w

as o

bser

ved

. The

str

onge

st e

ffec

ts

wer

e se

en

for

post

neon

ata

l res

pira

tory

mor

talit

y,

whi

ch in

crea

sed

cons

iste

ntly

with

incr

easi

ng q

uint

iles

of P

M10

(p

= 0

.013

). R

Rs

for

post

neon

ata

l res

pira

tory

m

orta

lity

for

the

high

est

vs t

he lo

wes

t qu

intil

e w

ere

2.41

(9

5% C

l: 1

.10-

5.2

8) f

or

PM

10,

3.9

1 (0

.90-

16.9

) fo

r S

O2,

and

1.2

0 (0

.37-

3.9

1) f

or N

Ox.

report no. 4/11

190

APP

END

IX 1

.4 -

LON

G-T

ERM

PA

RTI

CU

LATE

MA

TTER

(PM

) AN

D R

ESPI

RA

TOR

Y M

OR

BID

ITY.

Ref

eren

ce, L

ocat

ion,

Yea

rs, P

M In

dex,

M

ean

or M

edia

n (µ

g/m

3 ). St

udy

Des

crip

tion.

Mod

elin

g m

etho

ds: l

ags,

sm

ooth

ing,

co-

pollu

tant

s an

d co

varia

tes.

R

esul

ts a

nd C

omm

ents

.

G

REA

T B

RIT

AIN

Lu

nn e

t al

., 1

967

(L

unn

et a

l, 1

967)

S

heff

ield

, E

ngla

nd.

A s

tud

y a

naly

zed

the

asso

ciat

ion

betw

een

mea

sure

s of

P

M a

nd S

O2

and

res

pira

tory

illn

esse

s in

5-

and

6-y

ear

old

sc

hool

ch

ildre

n liv

ing

in f

our

area

s of

She

ffie

ld, E

ngla

nd.

Pos

itive

ass

ocia

tions

wer

e f

ound

be

twee

n a

ir po

llutio

n co

ncen

trat

ions

and

bot

h up

per

and

low

er r

esp

irato

ry

illne

ss. L

ow

er r

esp

irato

ry il

lnes

s w

as 3

3 to

56%

mor

e fr

eque

nt in

the

hig

her

pol

lutio

n ar

eas

than

in t

he lo

w-

pollu

tion

are

a (

p <

0.0

05).

Als

o, d

ecre

men

ts in

lung

fu

nctio

n, m

easu

red

by

spiro

met

ry te

sts,

wer

e cl

osel

y as

soci

ated

with

res

pira

tory

dis

ease

sym

ptom

rat

es.

Lu

nn e

t al

., 1

970

(L

unn

et a

l, 1

970)

E

ngla

nd,

196

3-19

64.

A

stu

dy

con

duct

ed

in E

ngla

nd b

etw

een

196

3 a

nd

196

4

ana

lyze

d th

e as

soci

atio

n b

etw

een

BS

and

SO

2 a

nd

resp

irato

ry il

lnes

ses

in 1

1-ye

ar-o

ld c

hild

ren

.

Res

ults

wer

e si

mila

r to

tho

se f

ound

for

the

yo

unge

r gr

oup.

On

the

basi

s of

the

resu

lts r

epor

ted,

it

appe

ared

tha

t in

cre

ased

fre

quen

cy o

f lo

wer

re

spira

tory

sym

ptom

s an

d de

crea

sed

lung

fun

ctio

n in

ch

ildre

n co

uld

occ

ur w

ith lo

ng-t

erm

exp

osur

es to

an

nual

BS

leve

ls in

the

ran

ge o

f 23

0 to

301

µg/

m3 a

nd

SO

2 le

vels

of

181

to 2

75 µ

g/m

3 . How

eve

r, it

was

no

ted

that

thes

e w

ere

only

ver

y ap

prox

imat

e ob

serv

ed-

effe

ct le

vels

bec

aus

e of

unc

erta

intie

s as

soci

ated

with

est

imat

ing

PM

mas

s ba

sed

on B

S

read

ings

.

SW

ITZE

RLA

ND

A

cker

man

n-Li

ebric

h et

al.

(199

6)

(Ack

erm

ann-

Lieb

rich

et a

l, 19

97)

eig

ht d

iffer

ent a

reas

fro

m S

witz

erla

nd.

The

aim

of

this

stu

dy

was

to

exam

ine

the

effe

cts

of lo

ng

term

exp

osur

e to

air

pollu

tant

s on

lun

g fu

nctio

n in

adu

lts,

taki

ng a

dva

ntag

e fr

om a

sam

ple

of 9

,651

su

bjec

ts a

ged

18 to

60

from

eig

ht d

iffer

ent a

reas

of

Sw

itzer

land

. F

VC

an

d F

EV

1 w

ere

regr

esse

d a

gain

st th

e n

atur

al lo

gari

thm

s of

hei

ght

, w

eig

ht,

age,

ag

e sq

uare

d, g

end

er,

educ

atio

nal

le

vel,

natio

nalit

y, a

nd w

ork

plac

e ex

posu

re.

The

res

ults

sug

gest

ed t

hat

a 10

µg/

m3 in

crea

se in

an

nual

ave

rag

e P

M10

was

ass

ocia

ted

with

a 3

.4

perc

ent d

ecre

ase

in F

VC

for

hea

lthy

neve

r sm

oker

s.

Res

ults

wer

e a

lso

cons

iste

nt a

nd

sig

nific

ant

for

NO

2 an

d S

O2,

but

less

for

O3.

report no. 4/11

191

IT

ALY

Aro

ssa

et a

l. (1

987)

(A

ross

a et

al,

198

7)

Tur

in, I

taly

, 19

80-

1983

.

In th

is s

tud

y, lu

ng

func

tion

of 1

,880

sch

ool

ch

ildre

n w

as

mea

sure

d in

Tur

in, I

taly

, du

ring

a ti

me

peri

od w

hen

both

T

SP

and

SO

2 w

ere

bei

ng

redu

ced

. Thr

ee a

reas

of

Tur

in

(cen

tral

city

, pe

riph

era

l are

a, a

nd

sub

urba

n a

rea)

wer

e st

udie

d d

urin

g th

e w

inte

rs o

f 19

80 to

19

81 a

nd 1

982

to

1983

. Eac

h ch

ild's

res

pira

tory

he

alth

was

ass

esse

d at

the

be

gin

nin

g a

nd

end

of

the

stud

y us

ing

a qu

estio

nna

ire

whi

ch a

lso

obta

ined

dem

ogra

phic

info

rmat

ion.

Lu

ng

func

tion

mea

sure

men

ts in

clud

ed F

VC

, F

EV

1, F

EF

25-7

5,

and

ME

F50

. Da

ily S

O2

and

TS

P m

easu

rem

ents

wer

e av

aila

ble

fro

m s

even

mon

itorin

g si

tes

in t

he a

rea.

A

GLM

an

alys

is a

djus

ted

for

sex

and

ant

hro

pom

etric

va

riab

les

was

use

d to

est

imat

e lu

ng f

unct

ion

valu

es.

The

pol

lutio

n da

ta c

onfir

med

tha

t th

e la

rge

SO

2 di

ffer

ence

s ac

ross

are

as in

198

0 to

198

1 w

ere

re

duce

d su

bsta

ntia

lly b

y 19

82 to

19

83. T

he

diff

eren

ces

in T

SP

rem

aine

d sm

all b

ut c

ons

tant

du

ring

the

time

peri

od.

Ave

rage

slo

pes

wer

e si

gnifi

can

tly h

igh

er w

ithin

the

city

of

Tur

in w

hen

com

pare

d w

ith t

he s

ubur

ban

area

, su

gges

ting

to th

e

auth

ors

that

a d

ecre

ase

in p

ollu

tion

(pr

imar

ily S

O2)

re

sulte

d in

an

impr

ovem

ent o

f lu

ng f

unct

ion

.

report no. 4/11

192

APP

END

IX 1

.5 -

LON

G-T

ERM

PA

RTI

CU

LATE

MA

TTER

(PM

) AN

D L

UN

G C

AN

CER

.

Ref

eren

ce, L

ocat

ion,

Yea

rs, P

M In

dex,

Mea

n or

Med

ian

(µg/

m3 ).

Stud

y D

escr

iptio

n. M

odel

ing

met

hods

: lag

s,

smoo

thin

g, c

o-po

lluta

nts

and

cova

riate

s.

Res

ults

and

Com

men

ts.

K

atso

uya

nni e

t al

., 1

991

(Kat

sou

yan

ni e

t al,

199

1).

A h

osp

ital-b

ase

d ca

se-c

ontr

ol s

tud

y w

as

unde

rtak

en in

Ath

ens

bet

wee

n 19

87

and

198

9

on 1

89 w

omen

with

lun

g ca

ncer

and

89

fem

ale

cont

rols

with

fra

ctur

es o

r ot

her

orth

ope

dic

cond

itio

ns. L

ifetim

e ex

posu

re to

air

pollu

tion

was

ass

esse

d b

y lin

king

blin

dly

lifel

ong

re

side

ntia

l and

em

plo

ymen

t ad

dres

ses

of a

ll su

bjec

ts w

ith o

bjec

tive

ly e

stim

ated

or

pres

umed

ai

r po

llutio

n le

vels

. RR

s w

ere

der

ive

d b

y m

ultip

le lo

gist

ic r

egr

essi

on m

odel

s ad

just

ed f

or

age.

Air

pol

lutio

n le

vels

wer

e a

ssoc

iate

d w

ith

incr

ease

d r

isk

for

lung

ca

ncer

but

the

age

-ad

just

ed R

R w

as s

mal

l an

d n

ot s

tatis

tica

lly

sign

ifica

nt.

Whe

reas

ther

e w

as n

o ef

fect

of

air

pollu

tion

amon

g no

n-sm

oker

s, a

n in

tera

ctio

n w

ith s

mok

ing

dura

tion

has

bee

n sh

ow

n. T

he in

tera

ctio

n w

as a

lmos

t ex

clus

ivel

y ac

cou

nte

d fo

r b

y th

e n

on-

aden

ocar

cino

ma

lung

can

cers

.

report no. 4/11

193

APPENDIX 1.6 - REFERENCES TO APPENDICES

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6. Katsouyanni K, Hatzakis A, Kalandidi A, Trichopoulos D (1990a) Short-term effects of atmospheric pollution on mortality in Athens. Arch Hellen Med 7: 126-132.

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8. Katsouyanni K, Pantazopoulou A, Touloumi G, Tselepidaki I, Moustris K, Asimakopoulos D, Poulopoulou G, Trichopoulos D (1993) Evidence for interaction between air pollution and high temperature in the causation of excess mortality. Arch Environ Health 48: 235-242.

9. Katsouyanni K, Trichopoulos D, Kalandidi A, Tomos P, Riboli E (1991) A case-control study of air pollution and tobacco smoking in lung cancer among women in Athens. Prev Med 20: 271-278.

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13. Spix C, Heinrich J, Dockery D, Schwartz J, Volksch G, Schwinkowski K, Collen C, Wichmann HE (1993) Air pollution and daily mortality in Erfurt, east Germany, 1980-1989. Environ Health Perspect 101: 518-526.

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14. Sunyer J, Saez M, Murillo C, Castellsague J, Martinez F, Anto JM (1993) Air pollution and emergency room admissions for chronic obstructive pulmonary disease: a 5-year study. Am J Epidemiol 137: 701-705.

15. Thurston GD, Ito K, Lippmann M, Hayes C (1989) Reexamination of London, England, mortality in relation to exposure to acidic aerosols during 1963-1972 winters. Environ Health Perspect 79: 73-82.

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