Stratified mortality risk estimation across the ozone distribution: interactions with PM _2.5 , NO ₂ , and population characteristics

Studies examining mortality risk related to long-term ozone (O₃) exposure, and the associated concentration response function, have yielded inconsistent results. In addition to different exposure metrics and averaging periods across studies, co-pollutant interactions and population characteristics varying with O₃ exposure level increase the complexity of estimating independent O₃ effects. We conducted a case-control study of Medicare beneficiaries, matching on O₃ exposure decile, to examine all-cause mortality risk along the entire U.S. annual average O₃ distribution during 2015-2016. We calculated odds ratios stratified by decile and examined demographic and co-pollutant characteristics within these deciles. Correlations between O₃, fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) were highly variable within deciles and across O₃ exposure metrics. Beneficiary- and zip code-level characteristics, including socioeconomic status (SES) and race/ethnicity, varied across O₃ and co-pollutant exposure combinations. Risk estimates for O₃ were generally null, but sensitive to stratification by demographic characteristics and co-pollutant concentrations including Medicaid-eligibility, age, sex, urbanicity, and PM_2.5 and NO₂ exposure levels. PM_2.5 was consistently associated with mortality within most O₃ exposure deciles. Whether our results reflect synergistic effects between O₃ and PM_2.5 and/or residual confounding of SES or co-pollutants, they may explain, at least in part, variability observed in previous studies.