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Background:

Mounting evidence has shown that long-term exposure to fine particulate matter [PM $\le 2.5\mathrm{\mu }\mathrm{m}$ in aerodynamic diameter (${\mathrm{PM}}_{2.5}$)] and ozone (${\mathrm{O}}_3$) can increase mortality. However, the health effects associated with long-term exposure to nitrogen dioxide (${\mathrm{NO}}_2$) are less clear, in particular the evidence is scarce for ${\mathrm{NO}}_2$ at low levels that are below the current international guidelines.

Methods:

We constructed a population-based full cohort comprising all Medicare beneficiaries (aged $\ge 65$, $N=\mathrm{13,590,387}$) 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 ${\mathrm{NO}}_2$, that is, with annual means below the current World Health Organization guidelines (i.e., $\le 21\text{\hspace{0.17em}ppb}$). We applied previously estimated spatially and temporally resolved ${\mathrm{NO}}_2$ 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 ${\mathrm{NO}}_2$ 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 ${\mathrm{NO}}_2$ over the study period. We observed an association between long-term exposure to low-level ${\mathrm{NO}}_2$ and all-cause mortality, with a $\text{hazard ratio\hspace{0.17em}}\left(\text{HR}\right)=$ 1.042 (95% CI: 1.040, 1.045) in single-pollutant models and a $\text{HR}=$ 1.047 (95% CI: 1.045, 1.049) in multipollutant models (adjusting for ${\mathrm{PM}}_{2.5}$ and ${\mathrm{O}}_3$), per $10\text{-ppb}$ increase in annual ${\mathrm{NO}}_2$ concentrations. The penalized spline indicates a linear exposure–response relationship across the entire ${\mathrm{NO}}_2$ exposure range. Medicare enrollees who were White, female, and residing in urban areas were more vulnerable to long-term ${\mathrm{NO}}_2$ exposure.

Conclusion:

Using a large and representative cohort, we provide epidemiological evidence that long-term exposure to ${\mathrm{NO}}_2$, 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 ${\mathrm{PM}}_{2.5}$ and ${\mathrm{O}}_3$ exposure. Improving air quality by reducing ${\mathrm{NO}}_2$ emissions, therefore, may yield significant health benefits. https://doi.org/10.1289/EHP9044