Long-term nitrogen dioxide exposure and cause-specific mortality in the U.S. Medicare population.

BACKGROUND: Since 1971, the annual National Ambient Air Quality Standard (NAAQS) for nitrogen dioxide (NO2) has remained at 53 ppb, the impact of long-term NO2 exposure on mortality is poorly understood. OBJECTIVES: We examined associations between long-term NO2 exposure (12-month moving average of NO2) below the annual NAAQS and cause-specific mortality among the older adults in the U.S. METHODS: Cox proportional-hazard models were used to estimate Hazard Ratio (HR) for cause-specific mortality associated with long-term NO2 exposures among about 50 million Medicare beneficiaries living within the conterminous U.S. from 2001 to 2008. RESULTS: A 10 ppb increase in NO2 was associated with increased mortality from all-cause (HR: 1.06; 95% CI: 1.05-1.06), cardiovascular (HR: 1.10; 95% CI: 1.10-1.11), respiratory disease (HR: 1.09; 95% CI: 1.08-1.11), and cancer (HR: 1.01; 95% CI: 1.00-1.02) adjusting for age, sex, race, ZIP code as strata ZIP code- and state-level socio-economic status (SES) as covariates, and PM2.5 exposure using a 2-stage approach. NO2 was also associated with elevated mortality from ischemic heart disease, cerebrovascular disease, congestive heart failure, chronic obstructive pulmonary disease, pneumonia, and lung cancer. We found no evidence of a threshold, with positive and significant HRs across the range of NO2 exposures for all causes of death examined. Exposure-response curves were linear for all-cause, supra-linear for cardiovascular-, and sub-linear for respiratory-related mortality. HRs were highest consistently among Black beneficiaries. CONCLUSIONS: Long-term NO2 exposure is associated with elevated risks of death by multiple causes, without evidence of a threshold response. Our findings raise concerns about the sufficiency of the annual NAAQS for NO2.

The impact of long-term PM2.5 exposure on specific causes of death: exposure-response curves and effect modification among 53 million U.S. Medicare beneficiaries.

BACKGROUND: The shape of the exposure-response curve for long-term ambient fine particulate (PM2.5) exposure and cause-specific mortality is poorly understood, especially for rural populations and underrepresented minorities. METHODS: We used hybrid machine learning and Cox proportional hazard models to assess the association of long-term PM2.5 exposures on specific causes of death for 53 million U.S. Medicare beneficiaries (aged ≥65) from 2000 to 2008. Models included strata for age, sex, race, and ZIP code and controlled for neighborhood socio-economic status (SES) in our main analyses, with approximately 4 billion person-months of follow-up, and additionally for warm season average of 1-h daily maximum ozone exposures in a sensitivity analysis. The impact of non-traffic PM2.5 on mortality was examined using two stage models of PM2.5 and nitrogen dioxide (NO2). RESULTS: A 10 µg /m3 increase in 12-month average PM2.5 prior to death was associated with a 5% increase in all-cause mortality, as well as an 8.8, 5.6, and 2.5% increase in all cardiovascular disease (CVD)-, all respiratory-, and all cancer deaths, respectively, in age, gender, race, ZIP code, and SES-adjusted models. PM2.5 exposures, however, were not associated with lung cancer mortality. Results were not sensitive to control for ozone exposures. PM2.5-mortality associations for CVD- and respiratory-related causes were positive and significant for beneficiaries irrespective of their sex, race, age, SES and urbanicity, with no evidence of a lower threshold for response or of lower Risk Ratios (RRs) at low PM2.5 levels. Associations between PM2.5 and CVD and respiratory mortality were linear and were higher for younger, Black and urban beneficiaries, but were largely similar by SES. Risks associated with non-traffic PM2.5 were lower than that for all PM2.5 and were null for respiratory and lung cancer-related deaths. CONCLUSIONS: PM2.5 was associated with mortality from CVD, respiratory, and all cancer, but not lung cancer. PM2.5-associated risks of CVD and respiratory mortality were similar across PM2.5 levels, with no evidence of a threshold. Blacks, urban, and younger beneficiaries were most vulnerable to the long-term impacts of PM2.5 on mortality.

Long-term NO2 exposures and cause-specific mortality in American older adults.

BACKGROUND: The impact of long-term exposure to nitrogen dioxide (NO2) on cause-specific mortality is poorly understood. OBJECTIVE: To assess mortality risks associated with long-term NO2 exposure and evaluate confounding of this association. METHODS: We examined the association between 12-month moving average NO2 exposure and cause-specific mortality in 14.1 million US Medicare beneficiaries between 2000 and 2008. Associations were examined using age, gender, and race-stratified and state-adjusted Poisson regression models. We assessed the potential for confounding by PM2.5 and behavioral covariates and unmeasured confounding by decomposing NO2 into its spatial and spatio-temporal components. RESULTS: We found significant associations between 12-month NO2 exposure and increased mortality from all-causes [risk ratio (RR): 1.052; 95% CI: 1.051, 1.054; per 10 ppb], cardiovascular (CVD) (1.133; 95% CI: 1.130, 1.137) and respiratory disease (1.050; 95% CI: 1.044, 1.056), all cancers (1.021; 95% CI: 1.017, 1.025), ischemic heart disease (IHD) (1.221; 95% CI: 1.217, 1.226), cerebrovascular (CBV) disease (1.092; 95% CI: 1.085, 1.100), and for the first time pneumonia (1.275; 95% CI: 1.263, 1.287). Associations generally remained positive and statistically significant after adjustment for PM2.5 and behavioral factors. CONCLUSIONS: Our findings provide additional evidence of the increased risk posed by long-term NO2 exposures on increased mortality from all-causes, CVD, respiratory disease, IHD, CBV, and cancer and provide new evidence of their impact on mortality from pneumonia. Unmeasured confounding of these associations was present, however, demonstrating the need to understand sources of this confounding.