Reply to Künzli and Tager Regarding Causality in PM2.5 Cohort Studies

analysis of multilevel analytic studies with applications to a study of air pollution. cumulative ambient concentrations of air pollutants: description and precision of methods used for an epi-demiologic study. association between air pollution and mortality in six U. Association between lifetime ambient ozone exposure and pulmonary function in college freshman-results of a pilot study. Kunzli and Tager suggest that my critique (1) of PM2.5 and mortality in long-term prospective cohort studies is full of inaccuracies and misconceptions about ecological studies. As in most arguments, there are issues on which there is agreement, others where there is disagreement, and some areas of misunderstanding. I will briefly discuss those relevant issues on which we disagree. I believe that the cohort studies are accurately described, that the ambient PM2.5 concentrations are inadequate surro-gates for individual-level exposure, and that these studies are subject to some biases and inaccuracies common to true ecological studies. In my paper (1), I suggested that risk estimates based on ambient concentration levels should be tested for plausibility using other studies with both individual-level exposure and response data, and I applied such a test. I presented evidence that short-term exposures in time-series studies are not coherent with long-term health effects and that long-term morbidity findings may not be coherent with mortality. I suggested that the Six Cities results might be confounded, using between-city differences in lung function as one example. I did not present the air pollution studies as being truly ecological. In my paper (1), I described the cohort studies asà mixed design incorporating both individual level data...and group-level data on ambient air pollution concentrations." More precise terms such as semiecological, or hybrid, or semi-individual may be helpful. In my opinion, a lack of consideration for the limitations inherent in ecological exposure variables has led to significant errors in interpretation. Kunzli and Tager appear to suggest that the pollution exposure variable is not ecological because it is derived from measurement (i.e., it is a "crude, average ambient concentration"). It is true that Brenner et al. (2) state that in "ecologic studies, the exposure status of groups is often defined by the proportion of individuals exposed." Kunzli and Tager apparently missed the word "often" or interpreted it as "always." Brenner et al. (2) go on to indicate that exposure characterized by a single common measure such as "area air pollution" is an ecologic exposure variable. We seem to agree that …