Long-term PM2.5 exposure and sepsis mortality in a US medicare cohort.

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 PM2.5 exposure and sepsis-related mortality. For each Medicare beneficiary (ages 65-120), we estimated the 12-month moving average PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 exposure is associated with elevated risks of sepsis-related mortality.

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 constituents and their sources on specific causes of death in a US Medicare cohort.

BACKGROUND: Our understanding of the impact of long-term exposures to PM2.5 constituents and sources on mortality is limited. OBJECTIVES: To examine associations between long-term exposures to PM2.5 constituents and sources and cause-specific mortality in US older adults. METHODS: We obtained demographic and mortality data for 15.4 million Medicare beneficiaries living within the conterminous United States (US) between 2000 and 2008. We assessed PM2.5 constituents exposures for each beneficiary and used factor analysis and residual-based methods to characterize PM2.5 sources and mixtures, respectively. In age-, sex-, race- and site- stratified Cox proportional hazard models adjusted for neighborhood socio-economic status (SES), we assessed associations of individual PM2.5 constituents, sources, and mixtures and cause-specific mortality and examined modification of these associations by participant demographics and location of residence. We assessed the robustness of our findings to additional adjustment for behavioral risk factors and to alternate exposure definitions and exposure windows. RESULTS: Hazard ratios (HR) were highest for all causes of death, except COPD, for PM2.5 constituents and the coal combustion-related PM2.5 components, with no evidence of confounding by behavioral covariates. We further found Pb and metal-related PM2.5 components to be significantly associated with increased HR of all causes of death, except COPD and lung cancer mortality, and nitrate (NO3-) and silicon (Si) and associated source-related PM2.5 components (traffic and soil, respectively) to be significantly associated with increased all-cause, CVD, respiratory and all cancer-related mortality HR. Associations for other examined constituents and mortality were inconsistent or largely null. Our analyses of mixtures were generally consistent with these findings. Mortality HRs were greatest for minority, especially Black, low-income urban, younger, and male beneficiaries. DISCUSSION: PM2.5 components related to coal combustion, traffic, and to a lesser extent, soil were strongly associated with mortality from CVD, respiratory disease, and cancer.

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 ozone exposures and cause-specific mortality in a US Medicare cohort.

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 PM2.5 (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 PM2.5, 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 PM2.5 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.