Response to loomis et al

air pollution as a predictor of mortality in a prospective study of US adults. Response to Loomis et al. I would like to address comments of Loomis et al. about inferences drawn from studies using group-level exposure variables , the use of the tobacco analogy, the application of Hill's criteria for causality (1), and the use of the Hertz-Picciotto criteria for evaluating studies (2). Whether the hybrid studies under discussion (3-5) are considered partly ecological (6,7) or individual level with exposure misclassifi-cation, bias (ecological or otherwise) is possible and should be checked. I hope that these discussions will lead to more considerations of the interplay between outcomes and confounders measured at the individual level and exposure measured at the group level. Loomis et al. suggest that the biases stemming from the "ecologic fallacy" do not apply to the PM2 5 air pollution studies because they are individual-level studies where exposure is measured with error. That is, by implication there is one PM exposure variable. But as indicated by Morgenstern (8,9), ecologic bias can arise when the mean of a group-level exposure variable has an effect on the individual-level exposure. By this definition there will be ecologic bias whenever the ecologic exposure variable has an effect, and when there is also an individual-level exposure effect in addition to the ecologic exposure effect. Unmeasured individual-level exposure to PM2 from all sources can be several orders ofmagnitude higher than ambient PM2.5 concentrations (10) because of extensive exposure to unmeasured sources such as tobacco and indoor combustion. These individual-level exposures vary for individuals within the group and contribute to the individual-level risk. The additional effect of ambient exposure provides the group-level component that leads to ecologic bias. The American Cancer Society (ACS) Study (4) and the Six Cities Study (3) suggest that an increase of about 20 pg/m3 PM235 results in a 20-30% increase in total mortality. I sought to test the consistency of these findings by comparing risk estimates based on group-level exposure estimates to those based on individual-level exposure to a similar but more thoroughly studied particulate (i.e., tobacco smoke). Applying the models developed in these studies to tobacco smoke, one can predict that a 20-pg/m3 difference in ambient PM2.5 between cities is too small to result in a measurable difference in overall mortality (6). If this is true, the differences in mortality between cities may be due to causes other than …