Understanding Unexpected Ozone–Health Associations: Are Secondary Oxidative Pollutants Key?

Despite the well-established mechanisms of how ozone (O3) results in adverse health, it is not uncommon for population-based epidemiology studies to find evidence that lower O3 levels are associated with higher risks of disease. Common explanations, such as the scavenging of O3 by nitric oxide near traffic and differential measurement error, cannot fully explain these unexpected associations. Therefore, we propose an alternate explanation for counter-to-hypothesized associations for O3. Specifically, we hypothesize that observed associations between higher levels of O3 and better health outcomes could be a consequence of the complex atmospheric chemistry that occurs in urban and near-urban areas. Low O3 could coincide with active oxidative processes, either through O3 consumption or parallel pathways involving other oxidants. Since these processes can generate toxic but unmeasured secondary products, it would be unsurprising to find inverse associations with O3. In this perspective, we highlight the key evidence supporting this hypothesis. In doing so, we hope that this perspective may inform future plans for air quality measurement and provide context for the interpretation of associations between O3 and health in epidemiology studies.