![Page 1: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/1.jpg)
Gevoeligheid maakt het verschil. Risico’s van milieu-blootstellingen in de bevolking
T I M N A W R O T , P h D .
C E N T R E F O R E N V I R O N M E N T A L S C I E N C E S , H a s s e l t U n i v e r s i t y
S e n i o r e n u n i v e r s i t e i t D i e p e n b e e k , 1 0 d e c e m b e r 2 0 1 2
![Page 2: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/2.jpg)
Wat gaan we doen?
• De geschiedenis van de epidemiologie
• Study designs
• Gevoeligheid in de bevolking: acute vs chronische
effecten, onderliggende aandoeningen
• Impact van het rookverbod in een gevoelige groep
• Een groot Limburgs geboortecohort
![Page 3: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/3.jpg)
What is Epidemiology?
Greek: EPI: upon
DEMOS: people
LOGOS: study
The study of how disease is distributed in populations and
the factors that influence or determine this distribution.
![Page 4: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/4.jpg)
Dag allemaal,
Epidemiologen leggen associaties dat doe ik ook heel de dag.
![Page 5: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/5.jpg)
Waarom data bij mensen?
• Extrapolation from animals to humans
risk estimates ? differ by 100.
• Range of exposure of interest
• Complexity of exposure
• Epidemiological data include the genetic diversity
inherent in human populations
![Page 6: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/6.jpg)
![Page 7: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/7.jpg)
“Molecular epidemiology”
Approach to incorporate molecular, cellular, and other biological measurements into epidemiologic research.
![Page 8: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/8.jpg)
Geschiedenis van de epidemiologie:
eerste klinische studie in 1747
• Earliest clinical trial in 1747
• Scurvy
• James Lind treated 12
scorbutic ship passengers on
a British navy ship with cider,
vinegar, sea water, oranges
and lemon
![Page 9: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/9.jpg)
Geschiedenis (2), 1854 John Snow
• 1854, when John Snow demonstrated the
transmission of cholera from contaminated water
• The majority of people who got ill used the Broad
Street Pump in London's Golden Square
• He removed the pump handle from the polluted well
and the spread of the disease stopped.
![Page 10: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/10.jpg)
John Snow
![Page 11: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/11.jpg)
Broad street pump
![Page 12: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/12.jpg)
Geschiedenis (3) Roken en longkanker 1954
![Page 13: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/13.jpg)
Richard Doll (1912-2005), who stopped smoking cigarettes at age 37, photographed aged 91 at the 2004 BMJ press conference on the 50-year results from his study of British doctors
![Page 14: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/14.jpg)
DOLL R, HILL AB. The mortality of doctors in relation to their smoking habits; a preliminary report.
Br Med J. 1954;1:1451-5.
![Page 15: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/15.jpg)
Mortality and smoking, first prospective evidence*
*Doll R et al. BMJ 1954; 26:1451-1455.
![Page 16: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/16.jpg)
Survival curve of 34 469 male British doctors*
*Doll R et al. BMJ 2004; 328:1519
![Page 17: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/17.jpg)
What is the health benefit of quitting smoking at age 60?
*Doll R et al. BMJ 2004; 328:1519
![Page 18: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/18.jpg)
Epidemiologie en het mechanistisch denken
• Epidemiology contributes to a causal understanding which is needed in prevention and treatment of disease or in the assessment of risks.
• Epidemiology can indicate causality even in the absence of a mechanistic understanding.
Treatment of scurvy far ahead of the knowledge of vitamin C (1747)
Association between dirty water and cholera, 44 years before Vibrio cholera was identified (1854)
Lung cancer and smoking (~1954)
![Page 19: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/19.jpg)
Epidemiological Study Designs
• Unit of observation = group Ecological study: statistics within geographical area
Community intervention trial
• Unit of observation = individual Experimental study
Observational study • Cohort study
• Case-control study
• Cross-sectional study
![Page 20: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/20.jpg)
Yearly Mean Mesothelioma Deaths 2000-2004
0 1 2 3 4 5 6
Death
s/1
06/y
Yearly mean asbestos consumption 1960-1969 (kg/head/year)
5.5
20 BEL
Flanders
106/3x106 Lin et al. Lancet 2007 369, 844-9
Belgium+Lux
53,790 T
Nawrot and Nemery. Lancet 2007, 369, 1692
![Page 21: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/21.jpg)
Ecological Fallacy
• Failure of ecological level associations to properly
reflect individual level associations
• e.g. hats and lung cancer
![Page 22: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/22.jpg)
Analytical Epidemiology
COHORT STUDY & CASE-CONTROL
STUDY
Unit of observation = individual
![Page 23: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/23.jpg)
Cohort Study Design
Population
Participants
without
disease of
interest
Exposed
Not
exposed
D
ND
D
ND
Time
![Page 24: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/24.jpg)
Case-Control Study
Study group
with disease
Exposed
Study group
without
disease
Exposed
Ratio diseased
Ratio not-diseased
O.R.
Not
exposed
Not
exposed
![Page 25: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/25.jpg)
Wat gaan we doen?
• De geschiedenis van de epidemiologie
• Study designs
• Gevoeligheid in de bevolking: acute vs chronische
effecten, onderliggende aandoeningen
• Impact van het rookverbod in een gevoelige groep
• Een groot Limburgs geboortecohort
![Page 26: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/26.jpg)
Hoe klein is fijn stof?
Uit: EPA, US Environment Protection Agency
“FIJN STOF”: verzamelnaam voor zeer kleine stofdeeltjes in de
lucht, kleiner dan één honderdste van een millimeter.
![Page 27: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/27.jpg)
![Page 28: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/28.jpg)
Brook R D et al. Circulation 2010;121:2331-2378
![Page 29: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/29.jpg)
Daily mortality according to temperature specific* PM10 quartiles
*temperature categories based on quintiles.
Non-traumatic deaths (n = 354 357)
0 20 40 60 80
<7°C
7-10°C
10-14°C
14-17°C
>17.0°C
130
140
150
160
170
PM10 (µg/m3)
Mean
nu
mb
er
of
death
s /
day
Nawrot, Torfs, Fierens et al. J Epidemiol Comm Health 2007, 61, 146-9
![Page 30: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/30.jpg)
Chronic vs acute effects and
Age
Severity
Event
![Page 31: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/31.jpg)
Brook R D et al. Circulation 2010;121:2331-2378
![Page 32: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/32.jpg)
Cardiovascular death and PM exposure
US (1994-1998): 6 years, 65.000 post-menopausal women free from CV disease Each increase of 10 ug/m³ PM 2,5: 76% higher risk for death from CVD
Miller et al. N Engl J Med. 2007
![Page 33: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/33.jpg)
Atherosclerosis and particulate exposure
Jacobs L. et al. Plos One 2011
Sun Q. et al. JAMA 2005.
0.0 0.5 1.0 1.5
0
50
100
150
200 r=0.28
p=0.01
Carbon load, µm²
Oxid
ized
LD
L,
U/L
0
50
100
150
200 r=-0.20
p=0.08
1 10 100 1000 10000
Distance to major road, m(Log scale)
Oxid
ized
LD
L,
U/L
Analysis adjusted for sex, age, socioeconomic status, LDL and
HDL cholesterol, BMI, type of diabetes, glycated haemoglobin,
statin use and blood leukocyte counts.
![Page 34: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/34.jpg)
Prospective study, 3 year folluw-up of 329 men
Outcome: Change in carotid intima-media thickness (CIMT)
Plaque status (number and size of plaques)
![Page 35: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/35.jpg)
Chronic vs acute effects and
Age
Severity
Event
![Page 36: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/36.jpg)
Case-crossover desing as trigger
Case only designs
comparison
reference
interval
index
interval
index
event
time
Usual frequency of exposure during past
Exposure in hazard period immediately before acute event
Maclure Am J Epidemiol 1991
![Page 37: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/37.jpg)
Baccarelli A et al. Lancet 2011
Community vs. Individual thinking
![Page 38: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/38.jpg)
Nawrot T et al. Lancet 2011
![Page 39: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/39.jpg)
Nawrot T et al. Lancet 2011
![Page 40: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/40.jpg)
Bloodvessel PFA cartridge
Agonist
Platelets
Collagen
Jacobs L et al. Environ Health Perspect 2011
![Page 41: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/41.jpg)
Jacobs L et al. Environ Res 2012
![Page 42: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/42.jpg)
Microvascular responses to short-term changes in
particulate air pollution in healthy persons
CRAE, µm
Exposure Time (lags) Model 1 (n=84) Model 2 (n=59) PM10 (per 10 µg/m³
increase)
2 hours -0.62 (-1.13; -0.11) a -0.25 (-0.68; 0.17)
4 hours -0.67 (-1.22; -0.13) a -0.30 (-0.75; 0.16)
6 hours -0.75 (-1.31; -0.18) a -0.32 (-0.79; 0.15)
24 hours -0.93 (-1.42; -0.45)c -0.50 (-0.92; -0.08)a
1 day -0.88 (-1.27; -0.48)c -0.54 (-0.89; -0.18)b
2 days -0.60 (-1.18; -0.02)a -0.40 (-0.95; 0.15)
BC (per 1 µg/m³ increase)
2 hours 0.24 (-0.57; 1.05) 0.15 (-0.54; 0.84)
4 hours 0.38 (-0.49; 1.26) 0.20 (-0.55; 0.96)
6 hours 0.52 (-0.47; 1.51) 0.29 (-0.58; 1.16)
24 hours -1.84 (-3.18; -0.51) -1.08 (-2.21; 0.04)
1 day -1.77 (-2.57; -0.97)c -1.18 (-1.19; -0.47)b
2 days -0.21 (-1.13; 0.71) -0.33 (-1.24; 0.57)
In model 1, estimates were adjusted for: gender, age, BMI, smoking habits of study participants, alcohol and
coffee consumption 24 hours prior to examination, time of the day and day of the week, outdoor temperature and
barometric pressure. Model 2 also includes, in addition to covariates in model 1, adjustment for systolic and
diastolic blood pressure and central retinal venular equivalent.
Louwies T, Int Panis L et al. submitted
![Page 43: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/43.jpg)
V O O R B E E L D E N V A N O N D E R L I G G E N D E A A N D O E N I N G E N
Gevoeligheid in de bevolking
![Page 44: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/44.jpg)
215 CF patients
A pulmonary exacerbation = use of intravenous / oral antibiotics at
home or in hospital. [Bilton D et al. Journal of Cystic Fibrosis 2011;10: S79–S81]
Patient groups (1): cystic fibrosis
Goeminne P, Kicinski M et al. Chest in press
![Page 45: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/45.jpg)
Patientgroup (2): lung transplant patients
Aim: Association between proximity of the home to major roads and incidence of chronic rejection and mortality in a cohort of lung transplants.
Methods • Follow-up (median 2.7 y) of 288 lung transplant patients. • Geocoding. • Cox regression
![Page 46: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/46.jpg)
Incidence of BOS and % survival in association with residential distance to a major road (1)
Nawrot T, De Vos R et al. Thorax 2011
Red line represents those living within 171 m (lowest tertile) of a major road
![Page 47: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/47.jpg)
Incidence of BOS and % survival in association with residential distance to a major road (1)
Nawrot T, De Vos R et al. Thorax 2011
Adjustements applied for sex, age, type of transpalntation (single or double
lung), infections, acute rejections, SES, time trend.
![Page 48: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/48.jpg)
![Page 49: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/49.jpg)
Air pollution and infant mortality in an affluent society: a case crossover design
Scheers H et al. Environ Health Perspect 2011
![Page 50: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/50.jpg)
![Page 51: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/51.jpg)
“The Barker Hypothesis”
Or :-
Fetal origins of adult disease hypothesis
Fetal programming hypothesis
Adverse environments in fetal life and early
childhood establish increased risk of disease
in adult life
![Page 52: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/52.jpg)
Dark areas
high infant mortality
rate (1901-1910)
and high death
rate from
coronary artery
disease (1959-78)
The early ‘Barker ‘studies
![Page 53: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/53.jpg)
Evidence of Programming in Human Populations Hertfordshire population
158
160
162
164
166
168
170
172
-5,5 -6,5 -7,5 -8,5 8.5+
Birthweight
SBP (mm Hg)
![Page 54: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/54.jpg)
Low Birthweight/Disproportionate size at Birth associated with:
Coronary artery disease
Hypertension
Glucose intolerance
Asthma in childhood
Immune dysfunction
Chronic renal failure
Raised cholesterol
Raised cortisol
Raised fibrinogen
![Page 55: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/55.jpg)
Epigenetica, de orkestleider van het DNA
genotype fenotype
![Page 56: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/56.jpg)
Epigenetica, de orkestleider van het DNA
genotype fenotype
![Page 57: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/57.jpg)
![Page 58: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/58.jpg)
Nederlandse hongerwinter
http://www.youtube.com/watch?v=le4HYO
VZCjo&list=PLP-
1fwOF25btswCjADmXq6ZMZpQYDJVWP
&index=2
![Page 59: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/59.jpg)
Heijmans B et al. PNAS 2008
![Page 60: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/60.jpg)
Early life exposures (1)
Janssen B, Godderis L, et al. Submitted
BACKGROUND: There is evidence that altered DNA methylation is an important epigenetic mechanism in prenatal programming and that developmental periods are sensitive to environmental stressors.
OBJECTIVE: We hypothesized that exposure to fine particles (PM2.5) during pregnancy could influence DNA methylation patterns of the placenta.
![Page 61: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/61.jpg)
Early life exposures (2)
Janssen B et al. Environ Health Perspect 2012
![Page 62: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/62.jpg)
Wat gaan we doen?
• De geschiedenis van de epidemiologie
• Study designs
• Gevoeligheid in de bevolking: acute vs chronische
effecten, onderliggende aandoeningen
• Impact van het rookverbod in een gevoelige groep
• Een groot Limburgs geboortecohort
![Page 63: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/63.jpg)
![Page 64: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/64.jpg)
Crystal E, et. al. Circulation 2012
![Page 65: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/65.jpg)
Rookverbod en myocardinfarct
Tabel: Vermeden sterfte door acuut myocardinfarct (AMI) in 2006
relatieve impact na invoering
sterfte aan AMI in 2005
Aantal overlijdens door AMI vermeden in 2006
man <60 -10,80% 362 39
vrouw <60 -34,80% 89 31
man >60 -8,20% 1970 162
vrouw >60 -7,80% 1572 123
![Page 66: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/66.jpg)
Triggers of preterm birth
![Page 67: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/67.jpg)
Crump C et al. JAMA 2011
![Page 68: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/68.jpg)
Triggers identified for preterm birth
Cox B, et. al. submitted
![Page 69: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/69.jpg)
Rate of preterm births and smoke free legislation
n=606 877
Cox B, et. al. BMJ in press
![Page 70: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/70.jpg)
Methods
The immediate effect of smoke-free legislation was modelled as a step function (step change), while the gradual effects were studied with an interaction term between the indicator variable and time (trend or slope change).
The models allowed for an underlying trend throughout the study period and were adjusted for infant sex, maternal age, parity, socio-economic status [municipality level / individual level (in sensitivity analysis)], national origin, level of urbanization of maternal residence, month of the year, day of the week, public holidays, apparent temperature, and PM10. Both for apparent temperature and for PM10 we calculated the average exposure on the day of delivery and the day before, and we allowed for non-linear associations with preterm birth by using natural cubic splines.
![Page 71: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/71.jpg)
Preterm birth and stepwise introduction of smoking ban
Model Legislation 2006 Legislation 2007 Legislation 2010
Step change Slope change Step change Slope change Step change Slope change
Spontaneous preterm delivery
2006 -3.24% -1.85%
n/a n/a n/a n/a (-4.40; -2.07)** (-2.42; -1.28)**
2007 n/a n/a -3.69% -2.16%
n/a n/a (-4.81; -2.55)** (-2.85; -1.46)**
2010 n/a n/a n/a n/a -3.36% -5.17%
(-4.73; -1.98)** (-7.36; -2.94)**
Final - - -3.13%
- - -2.65%
(-4.37; -1.87)** (-5.11; -0.13)**
Adjusted for underlying trend, newborn sex, maternal age, parity, socio-economic status, urbanization, month of the year, day of the week, public holidays, and short-term changes in apparent temperature and particulate air pollution (PM10). To put the relative changes in perspective, these changes correspond to a reduction of 6 preterm births per 1000 deliveries over the 5 study years (after 2007).
n=606 877
Cox B, et. al. BMJ in press
![Page 72: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/72.jpg)
-11.0 % (95% CI: −17.2 to −5.1) p = 0.001
Mackay DF, et. al. PlosMed. 2012
![Page 73: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/73.jpg)
El Paso
Pueblo
Page RL, et. al. J of womens’s Health. 2012
![Page 74: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/74.jpg)
![Page 75: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/75.jpg)
Wat gaan wij nog doen
Een gezondheidsstudie bij honderden Limburgse kinderen die we opvolgen van bij de geboorte tot jongvolwassenen.
![Page 76: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/76.jpg)
Human Life: John Wallis, 1790.
Risk: Exposures, inflammation,
oxidative stress, disease
suscpetibility, behavioral and socio-
economic determinants,…:
DURING ALL STAGES OF LIFE
To study chronic disease risk, traditionally recruited middle-aged subjects.
Inter generational study design: including exposure early in life and during critical life stages.
![Page 77: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/77.jpg)
Moeder
Placenta
Navelstrengbloed
Recruteren van pasgeborenen
![Page 78: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/78.jpg)
Placenta biopsies
![Page 79: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/79.jpg)
Meten van Biomerkers in Bloed en Weefsel
Telomeren
Mitochondrial DNA inhoud als een potentiële biomerker
van mitochondriale dysfunctie
DNA methylatie:
Veranderingen aan DNA die de
expressie van genen beïnvloeden
![Page 80: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/80.jpg)
Gezondheidsstudie bij jonge kinderen
Bloeddruk
![Page 81: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/81.jpg)
Gezondheidsstudie bij jonge kinderen
Halsslagader
![Page 82: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/82.jpg)
Gezondheidsstudie bij jonge kinderen
Microvasculatuur
![Page 83: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/83.jpg)
Gezondheidsstudie bij jonge kinderen
Speeksel
![Page 84: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/84.jpg)
Gezondheidsstudie bij jonge kinderen
Lengte
Gewicht
Buikomtrek
![Page 85: TIM NAWROT, PhD. - UHasselt - Universiteit van vandaagUHasselt... · TIM NAWROT, PhD. C E N T R E F O R ... DEMOS: people LOGOS: study ... Louwies T, Int Panis L et al. submitted](https://reader031.vdocuments.net/reader031/viewer/2022030706/5af33d097f8b9a8c3090d7d9/html5/thumbnails/85.jpg)
Wat onthouden we
Risico’s moeten we niet alleen interpreteren op het individueel niveau maar ook op het niveau van de bevolking.
De effecten van luchtvervuiling zijn veel sterker bij mensen met onderliggende aandoeningen.
Met meer en meer zekerheid kunnen we stellen dat vroeg in het leven een kritische periode is voor het ontwikkelen van ziekten later in het leven.
Het rookverbod heeft gunstige effecten vroeg in het leven.