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Determination of dose-response functions in CEEH

Determination of dose-response functions in CEEH. Jakob H. Bønløkke, MD, PhD CEEH and Dept. of Environmental and Occupational Medicine, Inst. of Public Health, Aarhus University, DK jb@mil.au.dk. Aarhus University in Århus. Use of D-R-functions.

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Determination of dose-response functions in CEEH

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  1. Determination of dose-response functions in CEEH • Jakob H. Bønløkke, MD, PhD • CEEH and Dept. of Environmental and Occupational Medicine, Inst. of Public Health, Aarhus University, DK • jb@mil.au.dk

  2. Aarhus University in Århus

  3. Use of D-R-functions • Dose/Exposure/Concentration - response relationships are crucial if health risks are to be trusted - and evaluated • Increased responses with increased doses, e.g. number of asthma attacks with increased ozone concentrations • or mortality rates ...

  4. Adjusted Mortality-Rate Ratios and Pollution Levels in the Six Cities Texte Texte Dockery et al NEJM 1993

  5. Cohort studies • Six Cities Study a prospective cohort study of 8000+ Americans with 15 years of follow-up using annual means of pollutants • Important basis of many D-R-functions used in models since together with studies by Pope and colleagues on 500000+ Americans

  6. Current estimates in CEEH • Primarily based on cohort studies • Example: • Relative risk for all-cause mortality: 1.05 for a 10 microg/m3 increase of PM2.5 . • “chronic death”

  7. Time series studies • Estimates of short-term effects • Correspondingly the D-R-function could be increase in mortality the day after an episode of high levels of a pollutant • “acute deaths” • By nature included in the long-term functions! (however poorly)

  8. Where are people exposed? • D-R-functions estimated outdoors at home • People spent most time indoors • and get extreme exposures during transport • and at work • By nature this too is reflected in the long-term function (however poorly because of “noise”) • - insufficient evidence to make good separate estimates for separate locations

  9. Other issues • Harvesting? • Thresholds? • Combined effects of several pollutants

  10. Does harvesting take place: Is an increase in mortality followed bya decrease shortly after?

  11. Schwartz Am J Epidemiol 2000

  12. Is there a threshold belowwhich no effect of particles onhealth has been observed?

  13. Daniels NMMAPS Am J Epidemiol 2000

  14. CEEH pollutants • No indications of thresholds for any pollutant • Ozone is poorly documented at low levels so currently it is being used as if there was a threshold at 70 microg/m3

  15. Are associations with particlessensitive to adjustment forco-pollutants?

  16. Samet NMMAPS NEJM 2001

  17. D-R-function between particulate matter and mortality is robust to correction for other pollutants • Not the case for all functions • And there are separate effects of different pollutants • Problem in estimating D-R-functions is that several pollutants are highly correlated

  18. Not only mortality ... • Respiratory symptoms • Medication • Absence from work • Cancer • Heart attacks, strokes, • Loss of IQ, etc.

  19. A matter of dose ... • Dose determines the response (?) • Dose a function of • concentration • time • uptake in body (usually via lungs) • clearing from body • uptake in target organ

  20. Thank you for your attention

  21. Suggested estimates in CEEH • RR for all-cause mortality: 1.05 for a 10 microg/m3 increase of PM2.5 . • RR among survivors of myocardial infarcts: 1.30 for a 10 microg/m3 increase of PM10. (Zanobetti and Schwartz EHP 2007)

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