hsci 483: children's health and the environment air pollution and children’s health may 12,...

HSCI 483: Children's Health and the Environment

Air Pollution and Children’s Health

May 12, 2015

Ryan AllenAssociate Professor

SFU Faculty of Health Sciences

Presentation Structure

• Two parts• Basic concepts, background, why is this

important?• (Epidemiologic) evidence of air pollution’s

effects on childhood health and development

LET’S START WITH SOME BASIC CONCEPTS AND BACKGROUND…

4

Particulate Matter (PM)

= PM2.5

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Population Attributable Fraction(aka Population Attributable Risk)

“…the proportional reduction in population disease or mortality that would occur if exposure to a risk factor were reduced to an alternative ideal exposure scenario (eg. no tobacco use).”

A function of the risk (e.g., RR, OR) and the fraction of the population that is exposed.

http://www.who.int/healthinfo/global_burden_disease/metrics_paf/en/

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Population Attributable Fraction(aka Population Attributable Risk)

Gordis, Epidemiology, 1996

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Individuals vs. Populations

“Interpretation In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of mycardial infarction, it is of similar magnitude (PAF 5-7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance.”

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“…a large number of people at a small risk may give rise to more cases of disease than the small number who are at a high risk.”

Or, in other words…

-Rose, Int. J. Epidemiol. 1985

“A large number of people at a small risk…”

Van Donkelaar, EHP, 2015

“…global population-weighted mean PM2.5 concentrations increased 0.55 ug/m3

/year [2.1%/year] from 1998 through 2012.

5.3 billion people

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• Proportion of world’s population relying on solid fuels declined from 53% in 1990 to 41% in 2010

• Absolute number of people relying on solid fuels has remained constant at ~2.8 billion people

Smith et al., Annu. Rev. Public Health 2014

“A large number of people at a small risk…”

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Recently Established “Facts”Location, location, location…

Karner et al., 2010, Environ Sci Tech

Wang et al., 2013, Atmos. Environ

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Location, Location, Location…

Brauer et al., “Traffic-Related Air Pollution and Health: A Canadian Perspsective on Scientific Evidence and Potential Exposure Mitigation Strategies”, 2012

1/3 of the Canadian population lives within 500 m of a highway or 100 m of a major road.

Nethery et al., 2009

CHAPS = Canadian Human Activity Patterns Survey (subset of women in Vancouver, aged 17-45).

Hours/day in microenvironments (weekdays only)

Model of time spent at/near home during pregnancy


“…our results indicate that pregnant women tend to spend more time at home during the latter stages of pregnancy…”

Cohen-Hubal et al., 2000


School: An Important Microenvironment

The ProvinceJanuary 5, 2012


Amram et al., 2011


48-hr personal exposure samples

54 kids at 4 schools


• California legislation (Senate Bill 352, Chapter 668, Statutes of 2003)

“The school district… identify both permitted and nonpermitted facilities…including, but not limited to, freeways and other busy traffic corridors, large agricultural operations, and railyards, within one-fourth of a mile [400 meters] of the proposed school site, that might reasonably be anticipated to emit hazardous air emissions...”

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“It is the opinion of the writing group that the overall evidence is

consistent with a causal relationship between PM2.5

exposure and cardiovascular morbidity and mortality.”

Recently Established “Facts”

AIR POLLUTION HAS EFFECTS BEYOND

THE LUNG!

Air pollution is now considered the most important environmental carcinogen (more important than second-hand smoke).

“The IARC Working Group unanimously classified outdoor air pollution and particulate matter from outdoor air pollution as carcinogenic to humans (IARC Group 1), based on sufficient evidence of carcinogenicity in humans and experimental animals and strong mechanistic evidence.”

Lancet Oncology, December 2013

Recently Established “Facts”

But what about kids?

• CVD, cancer are diseases of “old age”• So, what about effects in children?

Infant Mortality

Bell & Davis. EHP Supp 2001; 109:389-94; Schwartz, 1994

Infant Mortality

“In a country where infant mortality rates and air pollution levels are relatively low, ambient air pollution as measured by particulate matter contributes to a substantial fraction of infant death, especially for those due to sudden infant death syndrome and respiratory disease.“

Air Pollution and Health• Wide range of outcomes that can be evaluated in

research studies• More severe outcomes generally occur less frequently;

less severe outcomes generally occur more frequently• Significance, interpretation, policy implications

Mortality

Hospital admissions

Emergency visits

Functional limitation

Symptoms Clinical indicators

No adverse health effect

But what about kids?

• CVD, cancer are diseases of “old age”• So, what about effects in children?

– What if chronic exposure to air pollution also affected children’s growth and development?• Fetal growth?• Respiratory infections?• Neurological/cognitive development?• Lung growth?• Allergies?• Asthma development? (as opposed to asthma irritation)

Importance of Early Life Exposure

AGE

DE

VE

LOP

ME

NT

Examples: lung function, cognition


AGE

DE

VE

LOP

ME

NT

Earlier / more rapid decline

Area is grey is the “cumulative impact” on

health, quality of life, etc.


AGE

DE

VE

LOP

ME

NT

Failure to reach full “potential”


AGE

DE

VE

LOP

ME

NT

Relatively subtle changes in developmental “trajectory” early in life…

…may lead to substantial impairments…

…and a major “cumulative” impact over

the life course.

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“The developing human brain is inherently much more susceptible to injury caused by toxic agents than is the brain of an adult…

[Developmental] processes have to take place within a tightly controlled time frame, in which each developmental stage has to be reached on schedule and in the correct sequence…If a developmental process in the brain is halted or inhibited, there is little potential for later repair, and the consequences can therefore be permanent.”

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Kitaoka et al., 1996. Anat.Rec. 244 :207-213.Thurlbeck et al., 1975. Pathobiol. Annu. 5:1-34.

• Airways and lung development– Full number of generations of conducting

airways developed by 17 weeks gestation– Length and diameter of airways continue to

grow until 5 years of age– Approximately 150 million alveoli present at

birth– Alveoli fully developed (~300 million) by 2-3

years of age.

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Sears et al., NEJM, 2003

“These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.”


0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

4.50

5.00

Household Air Pollution Ambient Air Pollution

Attri

buta

ble

DA

LYs (

%)

4.3%

3.1 %

DALYs= Years of Life Lost (YLL) +

Years Lost Due to Disability (YLD)

0.00

500,000.00

1,000,000.00

1,500,000.00

2,000,000.00

2,500,000.00

3,000,000.00

3,500,000.00

4,000,000.00

Household Air Pollution Ambient Air Pollution

Attri

buta

ble

Dea

ths

CancersChronic Respiratory DiseasesCirculatory DiseasesInfections

3.48 M3.22 M

DEATHS

Data from GBD, http://vizhub.healthdata.org/gbd-compare/

Is it Prenatal Exposure? Postnatal Exposure? Both?

AGE

AIR

PO

LLU

TIO

N E

XP

OS

UR

E

PRENATAL EXPOSUREC

HIL

DH

OO

D E

XP

OS

UR

E

Is it Prenatal Exposure? Postnatal Exposure? Both?

AGE

AIR

PO

LLU

TIO

N E

XP

OS

UR

E

“Because of relatively high correlation between in utero and first-year exposures for many pollutants, we are unable to discern the relative importance of these exposure periods.”

Ginsberg et al., 2005

Extrathoracic Tracheobronchial Bronchioloes Pulmonary

Deposition/surface area of fine particles 2-4 x adults.

Children Are Not Small Adults

• Advantages to studying children– Fewer potentially confounding exposures

(occupational exposure, smoking)– Shorter duration for retrospective exposure

assessment

• Challenges in studying children– Some diagnoses unreliable in young children

(e.g. asthma)– Limitations in health testing (e.g. cognitive

testing in very young children)– Questionnaires rely on caretaker

Heinrich and Slama, 2007

Children Are Not Small Adults

Exposure “Contrasts”


• Risk estimates (relative risk, odds ratio) are expressed relative to some exposure contrast or gradient

• Relative risk =

• For example, risk among those living within 100 m of a major road (exposed) vs. risk among those living > 100 m from a major road (unexposed)

Risk in Exposed

Risk in Unexposed



• But what if exposure is not binary? What if there is no “unexposed” group?

• In these cases, risk is expressed per exposure contrast, e.g.,– Per 10 µg/m3

contrast in PM2.5

– How does risk at 10 ug/m3

compare to 20 ug/m3?

EXPOSURE

RIS

K

0 10 20

Cities with better air quality

Cities with poorer air quality

Dockery et al., NEJM, 1996

Adjusted for smoking, age, gender, BMI, education, occupational exposure

Cause of DeathMost vs. Least Polluted City

All1.26

(1.08-1.47)

Lung Cancer1.37

(0.81-2.31)

Cardiopulmonary1.37

(1.11-1.68)

All Other1.01

(0.79-1.30)


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0 10 20 30 40 50 60 70

VancouverHelsinki

San FranciscoMontreal

ChicagoLondon

Los AngelesMexico City

IstanbulMumbai

BeijingUlaanbaatar

Annual Average PM2.5 Concentration (ug/m3)

Example: “…for each 10-μg/m3 increase in PM2.5 exposure, birth weights declined by…48.4 grams.”

A 10 µg/m3 exposure

contrast is approximately the difference between typical concentrations in:

Mexico City vs. London

LA vs. San Francisco

Chicago vs. Vancouver

EFFECTS OF AIR POLLUTION ON CHILDREN’S DEVELOPMENT:

Fetal Growth & Development

Fetal Growth & Development• Indicators

– Birth weight (grams), Low birth weight (<2,500 grams), Small for gestational age (<10th %ile for gestational age), Pre-term birth (<37 weeks gestation)

• Disorders related to fetal growth and length of gestation are the leading cause of death in the first year of life in Canada

• Some evidence linking impaired fetal growth with metabolic syndrome, hypertension, diabetes mellitus, cardiovascular disease, and stroke in adulthood.– DOHaD

• Genetic factors account for 25-50% of the variation in birth weight, birth length, and head circumference.

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A Growing Research Area

Stieb et al., 2012

Growing Evidence of Solid Fuel Smoke’s

Effects of Fetal Growth

• Systematic review and meta-analysis • OR for LBW = 1.38 (1.25 – 1.52)• OR for stillbirth = 1.51 (1.23 – 1.85)• Mean reduction in birth weight = 96 g (69 – 124 g)**• “Because a majority of pregnant women in developing countries,

where rates of LBW and stillbirth are high, are heavily exposed to indoor air pollution, increased relative risk translates into substantial population attributable risks of 21% (LBW) and 26% (stillbirth)”

**Average effect of smoking during pregnancy on birth weight is a reduction of about 150-200 grams (Andres and Day. Seminars in Neonatology, 2000;5:231-41).

Intervention Studyof Reproductive Outcomes

69 pregnant women randomized to receive a chimney stove vs. 105 controls using open fires

Children of women using stoves had birth weight 89 g (95% CI: -27 – 204) greater than children of women using open fires

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Pregnant women enrolled into the study

Random Selection

Average birth weight among babies in this

group

Average birth weight among babies in this

group

No Air Filter

UGAAR Study

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UGAAR Study

http://www.eurasianet.org/node/66662

Adapted from Kannan et al., 2006

Air Pollution

Preterm Birth

Low Birth Weight

Intrauterine Growth

Restriction

Oxidative Stress

InflammationBlood

CoagulationEndothelial

FunctionHemodynamic

Responses

Transplacental Oxygen and Nutrient Transport

Possible Mechanisms


Neuropsychological Development

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Neuropsychological Development

Forns et al., 2012

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Prenatal Exposure and IQ

Perera et al., Pediatrics, 2009

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Attention “We examined

associations between black carbon and attention measures ascertained at 7-14 years of age among 174 children in a birth cohort based in Boston.”

“…we found associations between black carbon exposure and higher commission errors and slower reaction time. These associations were overall more apparent in boys than girls.”

Chiu et al., EHP, 2013

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Autism Risk factors for

autism are poorly understood A few recent studies

have linked early-life exposure to traffic-related air pollution with autism

Volk et al., JAMA Psychiatry, 2013

Case control study in California “Exposure to traffic-

related air pollution…during pregnancy and during the first year of life was associated with autism.”

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Confounding? Exposure determined, in part, by where

people live.

Several risk factors for neurodevelopmental impairments may also influence where individuals spend their time (i.e., self-selection):

“…maternal mental health status may be a potential confounder…because the increased risk of various adverse neurobehavioral outcomes in offspring…are associated with mothers’ mental health status, which may affect residential choice and thus determine the estimated residential exposures to ambient air pollution during pregnancy or early childhood.”

Block et al., Neurotoxicology, 2012

Possible Mechanisms Direct translocation of particles to the brain

and transfer across the blood brain barrier. BBB not fully developed until ~6 months of age. Post-mortem studies have found PM in the human

brain.

Circulating pro-inflammatory mediators. Activation of microglia, the brain’s resident innate

immune cells and regulators of neuroinflammation.

Key to normal brain function, but chronic activation can lead to neuron and cerebrovascular damage.

Block ML, Elder A, Auten RL, et al. The outdoor air pollution and brain health workshop. Neurotoxicology. Oct 2012;33(5):972-984. Block ML, Calderon-Garciduenas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. Sep 2009;32(9):506-516.


Respiratory Infections

Acute Lower Respiratory Infections

• Most important global cause of death in children under 5 (ALRIs 4 million deaths annually)

Smith, 2000; WHO, Fuel for Life, 2006

• Consistent evidence of associations between ALRI and solid fuel use (considered by WHO to be causally linked)

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“In a population heavily exposed to wood smoke from cooking, a reduction in exposure achieved with chimney stoves did not significantly reduce physician-diagnosed pneumonia for children younger than 18 months. The significant reduction of a third in severe pneumonia, however, if confirmed, could have important implications for reduction of child mortality.”

Chronic lung diseases

Cancer

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Respiratory Infections Cardiovascular

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Ambient PM and ALRI?

Mehta et al., Air Quality Atmosphere & Health, 2013


Lung Growth

• Prospective cohort study• 1,759 children from 12 communities• Measured lung function annually for 8 years

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Chronic Exposure and Lung DevelopmentThe California Children’s Health Study

• Impaired lung development associated with air pollution (strongest associations for traffic pollutants)

• Pollution-associated deficits were clinically significant by age 18

Gauderman et al, 2004

Chronic Exposure and Lung DevelopmentThe California Children’s Health Study

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Air Pollution and Lung Function Growth

• 110 children who moved away from communities in the Children’s Health Study

• “We conclude that changes in air pollution exposure during adolescent growth years have a measurable and potentially important effect on lung function growth and performance.”

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Early-Life Exposure

Morales et al., Thorax, 2015

• Lung function among 620 preschool children (4.5 years)

• Exposure modeled at residence location during pregnancy.

• “Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age.”


Asthma

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An Epidemic

Eder, NEJM, 2006

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Asthma Trends

Life and Breath, Respiratory Disease in Canada, 2007

Does air pollution cause asthma?

PROBABLY.

Does air pollution cause asthma?NO2 PM2.5

Anderson et al., Air Quality Atmosphere and Health, 2013

“These results are consistent with an effect of outdoor air pollution on asthma incidence.”

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An Important Role for Traffic Emissions

“How often do trucks pass through the street where you live, on weekdays?”


“Based on this evidence, the UK’s Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic.”

Gene x Environment

MacIntyre et al., EHP, 2014

“GSTP1 (the glutathione S-transferase pi gene) codes for an enzyme that metabolizes reactive oxygen species in the lung.”

Summary of Vancouver ResultsAir Pollution Effects on Children in a City with “Low” Levels of Air Pollution

MacIntyre et al., Epidemiology, 2011

• Arguably the best air quality of any major city in the world• Some evidence of associations for all of these effects• Evidence not entirely consistent across all pollutants or exposure

assessment methods• Traffic-related air pollution most consistently associated

Final Messages

1) The health impacts of air pollution are preventable.

2) The most effective way to reduce exposure to air pollution is to produce less air pollution.

3) Less pollution = Better health

hsci 483: children's health and the environment air pollution and children’s health may 12,...

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