This study involving an open cohort of all persons receiving Medicare, including those from small cities and rural areas, showed that long-term exposures to PM 2.5 and ozone were associated with an increased risk of death, even at levels below the current annual NAAQS for PM 2.5 . Furthermore, the study showed that black men and persons eligible to receive Medicaid had a much higher risk of death associated with exposure to air pollution than other subgroups. These findings suggest that lowering the annual NAAQS may produce important public health benefits overall, especially among self-identified racial minorities and people with low income.

The strengths of this study include the assessment of exposure with high spatial and temporal resolution, the use of a cohort of almost 61 million Medicare beneficiaries across the entire continental United States followed for up to 13 consecutive years, and the ability to perform subgroup analyses of the health effects of air pollution on groups of disadvantaged persons. However, Medicare claims do not include extensive individual-level data on behavioral risk factors, such as smoking and income, which could be important confounders. Still, our analysis of the MCBS subsample (Table S6 in the Supplementary Appendix) increased our level of confidence that the inability to adjust for these individual-level risk factors in the Medicare cohort did not lead to biased results (Section 5 in the Supplementary Appendix). In another study, we analyzed a similar Medicare subsample with detailed individual-level data on smoking, BMI, and many other potential confounders linked to Medicare claims.23 In that analysis, we found that for mortality and hospitalization, the risks of exposure to PM 2.5 were not sensitive to the additional control of individual-level variables that were not available in the whole Medicare population.

We also found that our results were robust when we excluded individual and ecologic covariates from the main analysis (Fig. S2 and Table S2 in the Supplementary Appendix), when we stratified age at entry into 3-year and 4-year categories rather than the 5 years used in the main analysis (Fig. S3 in the Supplementary Appendix), when we varied the estimation procedure (by means of a generalized estimating equation as opposed to mixed effects) (Tables S3 and S4 in the Supplementary Appendix), and when we used different types of statistical software (R, version 3.3.2, vs. SAS, version 9.4). Finally, we found that our results were consistent with others published in the literature (Section 6 in the Supplementary Appendix).5,17,24-28

There was a significant association between PM 2.5 exposure and mortality when the analysis was restricted to concentrations below 12 μg per cubic meter, with a steeper slope below that level. This association indicated that the health-benefit-per-unit decrease in the concentration of PM 2.5 is larger for PM 2.5 concentrations that are below the current annual NAAQS than the health benefit of decreases in PM 2.5 concentrations that are above that level. Similar, steeper concentration-response curves at low concentrations have been observed in previous studies.29 Moreover, we found no evidence of a threshold value — the concentration at which PM 2.5 exposure does not affect mortality — at concentrations as low as approximately 5 μg per cubic meter (Figure 3); this finding is similar to those of other studies.18,30

The current ozone standard for daily exposure is 70 ppb; there is no annual or seasonal standard. Our results strengthen the argument for establishing seasonal or annual standards. Moreover, whereas time-series studies have shown the short-term effects of ozone exposure, our results indicate that there are larger effect sizes for longer-term ozone exposure, including in locations where ozone concentrations never exceed 70 ppb. Unlike the American Cancer Society Cancer Prevention Study II,9,10 our study reported a linear connection between ozone concentration and mortality. This finding is probably the result of the interaction between PM 2.5 and ozone (Section 7 in the Supplementary Appendix). The significant, linear relationship between seasonal ozone levels and all-cause mortality indicates that current risk assessments,31-33 which incorporate only the acute effects of ozone exposure on deaths each day from respiratory mortality, may be substantially underestimating the contribution of ozone exposure to the total burden of disease.

The enormous sample size in this study, which includes the entire Medicare cohort, allowed for unprecedented accuracy in the estimation of risks among racial minorities and disadvantaged subgroups. The estimate of effect size for PM 2.5 exposure was greatest among male, black, and Medicaid-eligible persons. We also estimated risks in subgroups of persons who were eligible for Medicaid and in whites and blacks alone to ascertain whether the effect modifications according to race and Medicaid status were independent. We found that black persons who were not eligible for Medicaid (e.g., because of higher income) continued to have an increased risk of death from exposure to PM 2.5 (Fig. S4 in the Supplementary Appendix). In addition, we found that there was a difference in the health effects of PM 2.5 exposure between urban and rural populations, a finding that may be due to compositional differences in the particulates (Table S3 Supplementary Appendix).

Although the Medicare cohort includes only the population of persons 65 years of age or older, two thirds of all deaths in the United States occur in people in that age group. Although our exposure models had excellent out-of-sample predictive power on held-out monitors, they do have limitations. Error in exposure assessment remains an issue in this type of analysis and could attenuate effect estimates for air pollution.34

The overall association between air pollution and human health has been well documented since the publication of the landmark Harvard Six Cities Study in 1993.25 With air pollution declining, it is critical to estimate the health effects of low levels of air pollution — below the current NAAQS — to determine whether these levels are adequate to minimize the risk of death. Since the Clean Air Act requires the EPA to set air-quality standards that protect sensitive populations, it is also important to focus more effort on estimating effect sizes in potentially sensitive populations in order to inform regulatory policy going forward.