Determination of dose-response

functions in CEEHJakob 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

•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 ...

Dockery et al NEJM 1993

TexteTexte

Adjusted Mortality-Rate Ratios and Pollution Levels in the Six Cities

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

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”

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)

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

Other issues

•Harvesting?

•Thresholds?

•Combined effects of several pollutants

Does harvesting take place: Is an increase in mortality followed by

a decrease shortly after?

Schwartz Am J Epidemiol 2000

Is there a threshold belowwhich no effect of particles

onhealth has been observed?

Daniels NMMAPS Am J Epidemiol 2000

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

Are associations with particles

sensitive to adjustment forco-pollutants?

Samet NMMAPS NEJM 2001

•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

Not only mortality ...

•Respiratory symptoms

•Medication

•Absence from work

•Cancer

•Heart attacks, strokes,

•Loss of IQ, etc.

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

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)