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In the United States the Clean Air Act mandates that the Environmental Protection Agency set air quality standards to protect the most vulnerable of populations.A key focus of research is therefore to identify those individuals and communities at greatest risk from the health effects of ozone,particulate matter(PM)and other pollutants.For example,changes in inflammation and declines in lung function can be orders of magnitude difference between individuals.Research over the last decade has made it clear that intrinsic factors such as genes and pre-existing disease can determine whether an individual will have clinically relevant symptoms upon exposure to a pollutant.Major advances have been made in identifying specific genes or disease conditions by studying their role in determining susceptibility to single pollutants.For example genes such as GSTM1,suggested as a possible regulator of responses to ozone from mechanistic studies,have been confirmed through clinical studies and validated in epidemiologic association studies.Recent studies demonstrate the central contribution of factors that result in inflammation to increased risk from oxidant pollutants.Thus,while it would appear intuitive that individuals with pre-existing diseases such as asthma or cardiovascular disease would be more susceptible,recent work indicates that it is the accompanying airway or systemic inflammation that underlies the increased risk.This concept is reinforced by studies demonstrating heightened responses in ex-smokers and in obesity; two conditions where local or systemic inflammation is heightened but overt disease is missing.At the molecular level,microRNAs that can regulate gene expression of inflammatory genes and transcription factors such as Nrf-2 which can do the same are shown to be associated with responsiveness to ozone.Throughout all these studies an intricate link between oxidative stress status and inflammation is apparent.The work suggests that any factor that can stimulate inflammation may also result in susceptibility.In addition to these intrinsic factors,social factors also may play a role since exposure to pollutants is linked to economic status.