Long-Term Exposure to Low-Level [Formula: see text] and Mortality among the Elderly Population in the Southeastern United States

BACKGROUND: Mounting evidence has shown that long-term exposure to fine particulate matter [PM [Formula: see text] in aerodynamic diameter ([Formula: see text])] and ozone ([Formula: see text]) can increase mortality. However, the health effects associated with long-term exposure to nitrogen dioxide ([Formula: see text]) are less clear, in particular the evidence is scarce for [Formula: see text] at low levels that are below the current international guidelines. METHODS: We constructed a population-based full cohort comprising all Medicare beneficiaries (aged [Formula: see text] , [Formula: see text]) in the southeastern United States from 2000 to 2016, and we then further defined the below-guideline cohort that included only those who were always exposed to low-level [Formula: see text] , that is, with annual means below the current World Health Organization guidelines (i.e., [Formula: see text]). We applied previously estimated spatially and temporally resolved [Formula: see text] concentrations and assigned annual means to study participants based on their ZIP code of residence. Cox proportional hazards models were used to examine the association between long-term exposure to low-level [Formula: see text] and all-cause mortality, adjusting for potential confounders. RESULTS: About 71.1% of the Medicare beneficiaries in the southeastern United States were always exposed to low-level [Formula: see text] over the study period. We observed an association between long-term exposure to low-level [Formula: see text] and all-cause mortality, with a [Formula: see text] 1.042 (95% CI: 1.040, 1.045) in single-pollutant models and a [Formula: see text] 1.047 (95% CI: 1.045, 1.049) in multipollutant models (adjusting for [Formula: see text] and [Formula: see text]), per [Formula: see text] increase in annual [Formula: see text] concentrations. The penalized spline indicates a linear exposure–response relationship across the entire [Formula: see text] exposure range. Medicare enrollees who were White, female, and residing in urban areas were more vulnerable to long-term [Formula: see text] exposure. CONCLUSION: Using a large and representative cohort, we provide epidemiological evidence that long-term exposure to [Formula: see text] , even below the national and global ambient air quality guidelines, was approximately linearly associated with a higher risk of mortality among older adults, independent of [Formula: see text] and [Formula: see text] exposure. Improving air quality by reducing [Formula: see text] emissions, therefore, may yield significant health benefits. https://doi.org/10.1289/EHP9044