This article is a commentary on the following three studies: Pope CA 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA. 2002 Mar 6;287(9):1132-41. Pope CA 3rd, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation. 2004 Jan 6;109(1):71-7. Krewski D, Burnett RT, Goldberg MS, Hoover BK, Siemiatycki J, Jerrett M, Abrahamowicz M, White WH. Overview of the reanalysis of the Harvard Six Cities Study and American Cancer Society Study of Particulate Air Pollution and Mortality. J Toxicol Environ Health A. 2003 Aug 22–Oct 10;66(16–19):1507–51. While the short-term effects of air pollution have been extensively studied, the long-term effects, on the other hand, have been much less explored because studying them requires the establishment of large-scale cohorts in terms of both sample size and follow-up duration. The largest cohort study initiated for this purpose was that of the American Cancer Society (ACS), whose results were published in the mid-1990s. It involved several hundred thousand Americans living in the 50 states, the District of Columbia, and Puerto Rico, who were followed for 6 years to study the effects of pollution on cardiopulmonary mortality. Its results, along with those of another American cohort study—the Six Cities Study—played a major role in public debates surrounding the reference values proposed by the US EPA (United States Environmental Protection Agency) for particulate matter. Some participants in this debate then pointed out what they considered to be limitations of these studies: bias introduced by the failure to account for potential confounding factors (sedentary lifestyle, passive or active exposure to cigarette smoke, climatic factors) and suggested that the results obtained might have been different if alternative statistical models had been used. The US-EPA then came under significant pressure from industry representatives, politicians, and scientists to make the original data from these two studies available for further analysis. Harvard University and the American Cancer Society then proposed to the US-EPA that it commission a reanalysis of the data from the two studies by the Health Effects Institute (HEI), an independent organization funded equally by the US-EPA and the automotive industry. The HEI consequently appointed a panel of experts to issue a call for proposals for this reanalysis: a team of Canadian and American researchers, led by Daniel Krewski of the University of Ottawa, was selected to undertake the reanalysis. The purpose of this critical review is to present the main findings of the ACS regarding the long-term effects of air pollution, as well as those of the reanalysis initiated by the HEI. (Excerpt from the article)