The impact of chronic exposure to fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM_2.5)) on respiratory disease and lung cancer mortality is poorly understood. In a cohort of 18.9 million Medicare beneficiaries (4.2 million deaths) living across the conterminous United States between 2000 and 2008, we examined the association between chronic PM_2.5 exposure and cause-specific mortality. We evaluated confounding through adjustment for neighborhood behavioral covariates and decomposition of PM_2.5 into 2 spatiotemporal scales. We found significantly positive associations of 12-month moving average PM_2.5 exposures (per 10-μg/m³ increase) with respiratory, chronic obstructive pulmonary disease, and pneumonia mortality, with risk ratios ranging from 1.10 to 1.24. We also found significant PM_2.5-associated elevated risks for cardiovascular and lung cancer mortality. Risk ratios generally increased with longer moving averages; for example, an elevation in 60-month moving average PM_2.5 exposures was linked to 1.33 times the lung cancer mortality risk (95% confidence interval: 1.24, 1.40), as compared with 1.13 (95% confidence interval: 1.11, 1.15) for 12-month moving average exposures. Observed associations were robust in multivariable models, although evidence of unmeasured confounding remained. In this large cohort of US elderly, we provide important new evidence that long-term PM_2.5 exposure is significantly related to increased mortality from respiratory disease, lung cancer, and cardiovascular disease.

Background: The shape of the exposure-response curve for long-term ambient fine particulate (PM_2.5) 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 PM_2.5 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 PM_2.5 on mortality was examined using two stage models of PM_2.5 and nitrogen dioxide (NO₂). Results: A 10 μg /m³ increase in 12-month average PM_2.5 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. PM_2.5 exposures, however, were not associated with lung cancer mortality. Results were not sensitive to control for ozone exposures. PM_2.5-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 PM_2.5 levels. Associations between PM_2.5 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 PM_2.5 were lower than that for all PM_2.5 and were null for respiratory and lung cancer-related deaths. Conclusions: PM_2.5 was associated with mortality from CVD, respiratory, and all cancer, but not lung cancer. PM_2.5-associated risks of CVD and respiratory mortality were similar across PM_2.5 levels, with no evidence of a threshold. Blacks, urban, and younger beneficiaries were most vulnerable to the long-term impacts of PM_2.5 on mortality.

We examined the association of long-term, daily 1-h maximum O₃ (ozone) exposures on cause-specific mortality for 22.2 million US Medicare beneficiaries between 2000–2008. We modeled the association between O₃ and mortality using age-gender-race stratified log-linear regression models, adjusted for state of residence. We examined confounding by (1) adjusting for PM_2.5 (particles with aerodynamic diameters <2.5 μm) and NO₂ (nitrogen dioxide) exposures, temperature, and neighborhood-level characteristics and behaviors, and (2) decomposing O₃ into its temporal and spatio-temporal components and comparing estimated risk ratios. We also examined sensitivity of our results to alternate exposure measures based on warm-season 8-h daily maximum and 24-h average exposures. We found increased risks from long-term O₃ exposures to be strongest and most consistent for mortality from respiratory disease (1.030, 95% CI: 1.027, 1.034) (including COPD (chronic obstructive pulmonary disease)), CHF (congestive heart failure), and lung cancer (1.015, 95% CI: 1.010, 1.020), with no evidence of confounding by PM_2.5, NO₂, and temperature and with results similar across O₃ exposure measures. While significant, associations between long-term O₃ exposures and CVD (cardiovascular)-related mortality (1.005, 95% CI: 1.003, 1.007) were confounded by PM_2.5 and varied with the exposure measure, with associations no longer significantly positive when warm-season 8-h maximum or 24-h average O₃ was used to assess exposures. In this large study, we provide strong evidence that O₃ exposure is associated with mortality from respiratory-related causes and for the first-time, lung cancer, but raise questions regarding O₃-related impacts on CVD mortality. Our findings demonstrate the need to further identify potential confounders.

The impact of long-term exposure to nitrogen dioxide (NO2) on cause-specific mortality is poorly understood. To assess mortality risks associated with long-term NO2 exposure and evaluate confounding of this association. 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. 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. 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.

Background: Risk factors contributing to sepsis-related mortality include clinical conditions such as cardiovascular disease, chronic lung disease, and diabetes, all of which have also been shown to be associated with air pollution exposure. However, the impact of chronic exposure to air pollution on sepsis-related mortality has been little studied. Methods: In a cohort of 53 million Medicare beneficiaries (228,439 sepsis-related deaths) living across the conterminous United States between 2000 and 2008, we examined the association of long-term PM_2.5 exposure and sepsis-related mortality. For each Medicare beneficiary (ages 65–120), we estimated the 12-month moving average PM_2.5 concentration for the 12 month before death, for their ZIP code of residence using well validated GIS-based spatio-temporal models. Deaths were categorized as sepsis-related if they have ICD-10 codes for bacterial or other sepsis. We used Cox proportional hazard models to assess the association of long-term PM_2.5 exposure on sepsis-related mortality. Models included strata for age, sex, race, and ZIP code and controlled for neighborhood socio-economic status (SES). We also evaluated confounding through adjustment of neighborhood behavioral covariates. Results: A 10 μg/m³ increase in 12-month moving average PM_2.5 was associated with a 9.1% increased risk of sepsis mortality (95% CI: 3.6–14.9) in models adjusted for age, sex, race, ZIP code, and SES. HRs for PM_2.5 were higher and statistically significant for older (> 75), Black, and urban beneficiaries. In stratified analyses, null associations were found for younger beneficiaries (65–75), beneficiaries who lived in non-urban ZIP codes, and those residing in low-SES urban ZIP codes. Conclusions: Long-term PM_2.5 exposure is associated with elevated risks of sepsis-related mortality.