Long-Term Ozone Exposure and Mortality in a Large Prospective Study

Rationale: Tropospheric ozone (O-3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O-3 are scarce and inconclusive. Objectives: In this study, we examined associations between chronic ambient O-3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults. Methods: Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O-3 concentrations at the participant's residence from a hierarchical Bayesian space-time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 mu m [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates. Measurements and Main Results: In single-pollutant models, we observed significant positive associations between O-3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O-3 and all-cause (hazard ratio [HR] per 10 ppb, 1.02; 95% confidence interval [CI], 1.01-1.04), circulatory (HR, 1.03; 95% CI, 1.01-1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08-1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models. Conclusions: Findings derived from this large-scale prospective study suggest that long-term ambient O-3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O-3 concentrations.