To the Editor: In the report by Miller and colleagues on long-termexposure to air pollution and the incidence of cardiovascularevents in women (Feb. 1 issue),1 the authors state that theirrobust findings (hazard ratio for death from cardiovasculardisease, 1.76) cannot be explained by acute effects of particulatematter. Although particulate matter might subtly promote atherosclerosis,2their findings in no way illustrate synergistic, long-term healthconsequences of exposure beyond acute effects.
The largest portion of the observed cardiovascular morbidityand mortality is due to particulate matter as a "triggeringevent" within hours to weeks after exposure. Cohort studies1relate long-term levels of particulate matter to events butprovide no information regarding the time courses over whichexposures actually cause outcomes. The differences between theresults of time series (relative risk of death from cardiovasculardisease approximately 1.01), which can provide similar dataon mortality,3 and the results reported by Miller et al. areprimarily likely to be due to underestimation of the true riskby time series, for multiple reasons. Moreover, case–crossoverstudies4 show that the risks within a single hour after exposureare similar in magnitude to those reported by Miller et al.,that lowering pollution dramatically reduces mortality withinonly months,5 and that extending exposure lag-times to weeksyields findings similar to those of cohort studies. It is notbiologically plausible that long-term exposure would increasemortality by a factor of 76 (or even by a factor of 2) becauseof cumulative health responses beyond acute effects (hours toweeks in duration).
Robert D. Brook, M.D. University of Michigan Ann Arbor, MI 48106 robdbrok{at}umich.edu
Sanjay Rajagopalan, M.D. Ohio State University Columbus, OH 43210
References
Miller KA, Siscovick DS, Sheppard L, et al. Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med 2007;356:447-458. [Free Full Text]
Künzli N, Jerrett M, Mack WJ, et al. Ambient air pollution and atherosclerosis in Los Angeles. Environ Health Perspect 2005;113:201-206. [ISI][Medline]
Burnett RT, Dewanji A, Dominici F, Goldberg MS, Cohen A, Krewski D. On the relationship between time-series studies, dynamic population studies, and estimating loss of life due to short-term exposure to environmental risks. Environ Health Perspect 2003;111:1170-1174. [ISI][Medline]
Peters A, von Klot S, Heier M, et al. Exposure to traffic and the onset of myocardial infarction. N Engl J Med 2004;351:1721-1730. [Free Full Text]
Laden F, Schwartz J, Speizer FE, Dockery DW. Reduction in fine particulate air pollution and mortality: extended follow-up of the Harvard Six Cities study. Am J Respir Crit Care Med 2006;173:667-672. [Free Full Text]
To the Editor: Miller et al. overstate the risk of death fromcardiovascular disease associated with exposure to particulatematter of less than 2.5 µm in aerodynamic diameter (PM2.5).The exposure increment of 10 µg per cubic meter for PM2.5used in the study is not available for most American cities.This exposure increment has been used correctly to describebetween-city exposures to PM2.51 or within-city exposures inLos Angeles,2 a megalopolis with unusually variable levels ofPM2.5. The actual increment for PM2.5 within most cities wouldbe much less. With 62 PM2.5 monitors covering 16 metropolitanareas around New York City,3 the 10th to 90th percentile exposureincrement is 3.23 µg per cubic meter. The 10th to 90thpercentile range of within-city deviations reported by Milleret al. is 3.3 µg per cubic meter. The authors also reportthat the within-city and between-city regression coefficientsare different (P=0.07), probably because of the variation inPM2.5 across the United States, which is mostly due to secondarysulfate levels, whereas the variation within cities arises fromtraffic sources. The toxicity of these mixtures differs,4 andthe exposure increment used for interpreting the hazard ratioshould reflect this difference. Using an exposure incrementof 3.3 µg per cubic meter on the basis of data for NewYork City and data from the study by Miller et al. yields ahazard ratio for death from cardiovascular disease of 1.31,not 2.28, as reported, which is consistent with prior research.1,2
Michael Jerrett, Ph.D. University of California Berkeley, CA 94720-7360 jerrett{at}berkeley.edu
Richard T. Burnett, Ph.D. Health Canada Ottawa, ON K1A 0K9, Canada
References
Pope CA III, Burnett RT, Thurston GD, et al. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 2004;109:71-77. [Free Full Text]
Jerrett M, Burnett RT, Ma RJ, et al. Spatial analysis of air pollution and mortality in Los Angeles. Epidemiology 2005;16:727-736. [CrossRef][ISI][Medline]
Ross Z, Jerrett M, Ito K, Tempalski B, Thurston G. A land use regression model for predicting fine particulate matter concentrations in the New York City region. Atmos Environ 2007;41:2255-2269. [CrossRef]
Schlesinger RB, Kunzli N, Hidy GM, Gotschi T, Jerrett M. The health relevance of ambient particulate matter characteristics: coherence of toxicological and epidemiological inferences. Inhal Toxicol 2006;18:95-125. [CrossRef][ISI][Medline]
The authors reply: The correspondents comment on the magnitudeof the risk estimate in our study, emphasizing the mortalityresults. Our primary hypothesis concerned the effect of fineparticulate matter on all incident cardiovascular events, forwhich the hazard ratio was 1.24 (95% confidence interval, 1.09to 1.41). Beyond exposure considerations, there are importantdifferences between prior studies and our research regardingthe population under study and the outcomes assessed.
Brook and Rajagopalan suggest that the effects on mortalitywe reported can be ascribed entirely to short-term exposure.Indeed, acute effects of air pollution are important and warrantadditional study. Cohort studies cannot easily distinguish betweenacute and long-term effects, since such studies reflect bothdifferent time courses of the underlying exposure distributionand different exposure–risk relationships.1,2 The cohortdesign suggests that long-term exposure is important, and thetoxicologic database3,4 suggests that air pollution may promoteatherosclerosis. Additional research is needed to determinewhether different time scales of exposure share pathophysiologicalunderpinnings.
Jerrett and Burnett are concerned that our use of an exposureincrement of 10 µg per cubic meter for PM2.5 providesan exaggerated estimate of the effect of particulate matter.For ease of comparison with published results from studies ofprevious national cohorts,5 we reported estimates using theexposure increment conventionally used in those studies. Theincrement of 10 µg per cubic meter lies well within therange of the individual exposure increments (3.4 to 28.3 µgper cubic meter; 10th to 90th percentile, 9.1 to 18.3) amongparticipants in the Women's Health Initiative ObservationalStudy. Since we found no reason to doubt a linear relationshipbetween pollutants and effects, readers can and should scalethe exposure increment to their own scientific context.
We agree with Jerrett and Burnett that the sources and componentsof particulate matter are likely to be important for determiningtoxicity and that much variation within cities is attributableto traffic sources. Our study, like prior work, does not providespecific guidance on sources and components.
Joel D. Kaufman, M.D., M.P.H. Kristin A. Miller, M.S. LianneSheppard, Ph.D. University of Washington Seattle, WA 98195 joelk{at}u.washington.edu
References
Haneuse S, Wakefield J, Sheppard L. The interpretation of exposure effect estimates in chronic air pollution studies. Stat Med (in press).
Künzli N, Medina S, Kaiser R, Quenel P, Horak F Jr, Studnicka M. Assessment of deaths attributable to air pollution: should we use risk estimates based on time series or on cohort studies? Am J Epidemiol 2001;153:1050-1055. [Free Full Text]
Sun Q, Wang A, Jin X, et al. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA 2005;294:3003-3010. [Free Full Text]
Suwa T, Hogg JC, Quinlan KB, Ohgami A, Vincent R, van Eeden SF. Particulate air pollution induces progression of atherosclerosis. J Am Coll Cardiol 2002;39:935-942. [Free Full Text]
Pope CA III, Burnett RT, Thun MJ, et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002;287:1132-1141. [Free Full Text]
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