Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM_2.5Transition Metals and Oxidative Potential

Background: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O₃and NO₂) and fine particulate air pollution (PM_2.5). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM_2.5is more capable of causing oxidative stress. Methods: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM_2.5components and oxidative potential. O_xexposures (i.e., the redox-weighted average of O₃and NO₂) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average O_xand mortality outcomes across strata of transition metals and sulfur in PM_2.5and three measures of PM_2.5oxidative potential adjusting for possible confounding factors. Results: Associations between O_xand mortality were consistently stronger in regions with elevated PM_2.5transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in O_xwas associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OP^GSH) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OP^GSHlevels below the median (interaction P value <0.001). Conclusion: Spatial variations in PM_2.5composition and oxidative potential may contribute to heterogeneity in the observed health impacts of long-term exposures to oxidant gases.