Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis

Objective: To investigate potential interactive effects of fine particulate matter (PM_2.5) and ozone (O₃) on daily mortality at global level. Design: Two stage time series analysis. Setting: 372 cities across 19 countries and regions. Population: Daily counts of deaths from all causes, cardiovascular disease, and respiratory disease. Main outcome measure: Daily mortality data during 1994-2020. Stratified analyses by co-pollutant exposures and synergy index (>1 denotes the combined effect of pollutants is greater than individual effects) were applied to explore the interaction between PM_2.5 and O₃ in association with mortality. Results: During the study period across the 372 cities, 19.3 million deaths were attributable to all causes, 5.3 million to cardiovascular disease, and 1.9 million to respiratory disease. The risk of total mortality for a 10 μg/m³ increment in PM_2.5 (lag 0-1 days) ranged from 0.47% (95% confidence interval 0.26% to 0.67%) to 1.25% (1.02% to 1.48%) from the lowest to highest fourths of O₃ concentration; and for a 10 μg/m³ increase in O₃ ranged from 0.04% (-0.09% to 0.16%) to 0.29% (0.18% to 0.39%) from the lowest to highest fourths of PM_2.5 concentration, with significant differences between strata (P for interaction <0.001). A significant synergistic interaction was also identified between PM_2.5 and O₃ for total mortality, with a synergy index of 1.93 (95% confidence interval 1.47 to 3.34). Subgroup analyses showed that interactions between PM_2.5 and O₃ on all three mortality endpoints were more prominent in high latitude regions and during cold seasons. Conclusion: The findings of this study suggest a synergistic effect of PM_2.5 and O₃ on total, cardiovascular, and respiratory mortality, indicating the benefit of coordinated control strategies for both pollutants.