Evaluating Potential Response-Modifying Factors for Associations between Ozone and Health Outcomes: A Weight-of-Evidence Approach

Background: Epidemiologic and experimental studies have reported a variety of health effects in response to ozone (O-3) exposure, and some have indicated that certain populations may be at increased or decreased risk of O-3-related health effects. Objectives: We sought to identify potential response-modifying factors to determine whether specific groups of the population or life stages are at increased or decreased risk of O-3-related health effects using a weight-of-evidence approach. Methods: Epidemiologic, experimental, and exposure science studies of potential factors that may modify the relationship between O3 and health effects were identified in U. S. Environmental Protection Agency's 2013 Integrated Science Assessment for Ozone and Related Photochemical Oxidants. Scientific evidence from studies that examined factors that may influence risk were integrated across disciplines to evaluate consistency, coherence, and biological plausibility of effects. The factors identified were then classified using a weight-of-evidence approach to conclude whether a specific factor modified the response of a population or life stage, resulting in an increased or decreased risk of O-3-related health effects. Discussion: We found "adequate" evidence that populations with certain genotypes, preexisting asthma, or reduced intake of certain nutrients, as well as different life stages or outdoor workers, are at increased risk of O-3-related health effects. In addition, we identified other factors (i.e., sex, socioeconomic status, and obesity) for which there was "suggestive" evidence that they may increase the risk of O-3-related health effects. Conclusions: Using a weight-of-evidence approach, we identified a diverse group of factors that should be considered when characterizing the overall risk of health effects associated with exposures to ambient O-3.