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.

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.

Smoking and olfactory dysfunction: A systematic literature review and meta-analysis.

OBJECTIVES/HYPOTHESIS: A systematic review and meta-analysis of the literature was undertaken, examining the association between tobacco smoking and olfactory function in humans, utilizing PubMed and Web of Science (1970-2015) as data sources. STUDY DESIGN: Systematic literature review and meta-analysis. METHODS: This database review of studies of smoking and olfaction, with a focus on identifying high-quality studies (based on modified versions of the Newcastle-Ottawa Scale), used validated olfactory tests among the generally healthy population. RESULTS: We identified 11 studies meeting inclusion criteria. Of 10 cross-sectional studies, two were excluded from meta-analysis because the cohorts they studied were included in another article in the review. In meta-analysis, current smokers had substantially higher odds of olfactory dysfunction compared to never smokers (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.37-1.85). In contrast, former smokers were found to have no difference in risk of impaired olfaction compared to never smokers (OR = 1.05, 95% CI = 0.91-1.21). The single longitudinal study reviewed found a trend toward increased risk of olfactory decline over time in ever smokers; this trend was stronger in current as compared to former smokers. CONCLUSIONS: Current smoking, but not former smoking, is associated with significantly increased risk of olfactory dysfunction, suggesting that the effects of smoking on olfaction may be reversible. Future studies that prospectively evaluate the impact of smoking cessation on improvement in olfactory function are warranted. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:1753-1761, 2017.

Long-Term PM2.5 Exposure and Respiratory, Cancer, and Cardiovascular Mortality in Older US Adults.

The impact of chronic exposure to fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5)) 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 PM2.5 exposure and cause-specific mortality. We evaluated confounding through adjustment for neighborhood behavioral covariates and decomposition of PM2.5 into 2 spatiotemporal scales. We found significantly positive associations of 12-month moving average PM2.5 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 PM2.5-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 PM2.5 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 PM2.5 exposure is significantly related to increased mortality from respiratory disease, lung cancer, and cardiovascular disease.

Fine particulate matter exposure and olfactory dysfunction among urban-dwelling older US adults.

OBJECTIVES: The olfactory nerve is anatomically susceptible to injury from pollution in inspired air, but there are no large-scale epidemiologic studies investigating this relationship. METHODS: Cross-sectional study using data from the National Social Life, Health, and Aging Project, a representative sample of home-dwelling US adults age 57-85 years. Olfactory function was tested using a validated 5-item odor identification test (Sniffin' Sticks). Exposure to fine particulate matter (PM2.5) at each respondent's home was estimated as 1-12 month moving averages prior to olfactory assessment using validated spatio-temporal models. RESULTS: Olfactory dysfunction was significantly associated with PM2.5 exposures averaged over 3-12 months in urban-dwelling respondents. The strongest effect was for 6 month average exposure (per 1-IQR increase in PM2.5: OR 1.28, 95% CI 1.05, 1.55) adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and the season. Interestingly, the most deleterious effects were observed among the youngest respondents, 57-64 years old, and those living in the northeast and south. CONCLUSIONS: We show for the first time that air pollution exposure is associated with poor olfaction among urban-living, older US adults.

Nitrogen dioxide pollution exposure is associated with olfactory dysfunction in older U.S. adults.

BACKGROUND: Olfactory dysfunction has profound effects on quality of life, physical and social function, and mortality itself. Nitrogen dioxide (NO2 ) is a pervasive air pollutant that is associated with respiratory diseases. Given the olfactory nerve's anatomic exposure to airborne pollutants, we investigated the relationship between NO2 exposure and olfactory dysfunction. METHODS: The ability to identify odors was evaluated using a validated test in respondents from the National Social Life, Health, and Aging Project (NSHAP), a representative probability sample of home-dwelling, older U.S. adults age 57 to 85 years. Exposure to NO2 pollution was assessed using measurements obtained from the U.S. Environmental Protection Agency (EPA) Aerometric Information Retrieval System (AIRS) ambient monitoring site closest to each respondent's home. We tested the association between NO2 exposure and olfactory dysfunction using multivariate logistic regression. RESULTS: Among older adults in the United States, 22.6% had impaired olfactory function, defined as ≤3 correct (out of 5) on the odor identification test. Median NO2 exposure during the 365 days prior to the interview date was 14.7 ppb (interquartile range [IQR], 10.8 to 19.7 ppb). An IQR increase in NO2 exposure was associated with increased odds of olfactory dysfunction (OR, 1.35; 95% CI, 1.07 to 1.72), adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and season of the home interview (n = 1823). CONCLUSION: We show for the first time that NO2 exposure is associated with olfactory dysfunction in older U.S. adults. These results suggest an important role for NO2 exposure on olfactory dysfunction, and, potentially, nasal disease more broadly.

Air pollution and homocysteine: more evidence that oxidative stress-related genes modify effects of particulate air pollution.

BACKGROUND: Ambient particles are associated with cardiovascular events and recently with total plasma homocysteine. High total plasma homocysteine is a risk for human health. However, the biologic mechanisms are not fully understood. One of the putative pathways is through oxidative stress. We aimed to examine whether associations of PM2.5 and black carbon with homocysteine were modified by genotypes including HFE H63D, C282Y, CAT (rs480575, rs1001179, rs2284367, and rs2300181), NQO1 (rs1800566), GSTP1 I105V, GSTM1, GSTT1 (deletion vs. nondeletion), and HMOX-1 (any short vs. both long). We attempted to replicate identified genes in an analysis of heart rate variability and in other outcomes reported in the literature. METHODS: Study subjects were 1000 white non-Hispanic men in the Boston area, participating in a cohort study of aging. PM2.5, black carbon, total plasma homocysteine, and other covariates were measured at several points in time between 1995 and 2006. We fit mixed models to examine effect modification of genes on associations of pollution with total plasma homocysteine. RESULTS: Interquartile range increases in PM2.5 and black carbon (7-day moving averages) were associated with 1.5% (95% confidence interval = 0.2% to 2.8%) and 2.2% (0.6% to 3.9%) increases in total plasma homocysteine, respectively. GSTT1 and HFE C282Y modified effects of black carbon on total plasma homocysteine, and HFE C282Y and CAT (rs2300181) modified effects of PM2.5 on homocysteine. Several genotypes marginally modified effects of PM2.5 and black carbon on various endpoints. All genes with significant interactions with particulate air pollution had modest main effects on total plasma homocysteine. CONCLUSIONS: : Effects of PM2.5 and black carbon on various endpoints appeared to be mediated by genes related to oxidative stress pathways.

Characterization of particulate and gas exposures of sensitive subpopulations living in Baltimore and Boston.

Personal exposures to particulate and gaseous pollutants and corresponding ambient concentrations were measured for 56 subjects living in Baltimore, Maryland, and 43 subjects living in Boston, Massachusetts. The 3 Baltimore cohorts consisted of 20 healthy older adults (seniors), 21 children, and 15 individuals with physician-diagnosed chronic obstructive pulmonary disease (COPD*). The 2 Boston cohorts were 20 healthy seniors and 23 children. All children were 9 to 13 years of age; seniors were 65 years of age or older; and the COPD participants had moderate to severe physician-diagnosed COPD. Personal exposures to particulate matter with aerodynamic diameters less than 2.5 microm (PM2.5), sulfate (SO(4)2-), elemental carbon (EC), ozone (03), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were measured simultaneously for 24 hours/day. All subjects were monitored for 8 to 12 consecutive days. The primary objectives of this study were (1) to characterize the personal particulate and gaseous exposures for individuals sensitive to PM health effects and (2) to assess the appropriateness of exposure assessment strategies for use in PM epidemiologic studies. Personal exposures to multiple pollutants and ambient concentrations were measured for subjects from each cohort from each location. Pollutant data were analyzed using correlation and mixed-model regression analyses. In Baltimore, personal PM2.5 exposures tended to be comparable to (and frequently lower than) corresponding ambient concentrations; in Boston, the personal exposures were frequently higher. Overall, personal exposures to the gaseous pollutants, especially O3 and SO2, were considerably lower than corresponding ambient concentrations because of the lack of indoor sources for these gases and their high removal rate on indoor surfaces. Further, the impact of ambient particles on personal exposure (the infiltration factor) and differences in infiltration factor by city, season, and cohort were investigated. No difference in infiltration factor was found among the cohorts, which suggests that all subjects were exposed to the same fraction of ambient PM2.5 for a given ambient concentration. In addition, the results show significant correlations between ambient PM2.5 concentrations and corresponding personal exposures over time and provide further indication that ambient gaseous pollutant concentrations may be better surrogates for personal PM2.5 exposures, especially personal exposures to PM2.5 of ambient origin, than their respective personal exposures. These results have important implications for PM health effects studies that use regression models including both ambient PM2.5 and gaseous pollutant concentrations as independent variables, because both parameters may be serving as surrogates for PM2.5 exposures.

Assessing the importance of different exposure metrics and time-activity data to predict 24-H personal PM2.5 exposures.

Personal PM(2.5) data from two recent exposure studies, the Scripted Activity Study and the Older Adults Study, were used to develop models predicting 24-h personal PM(2.5) exposures. Both studies were conducted concurrently in the summer of 1998 and the winter of 1999 in Baltimore, MD. In the Scripted Activity Study, 1-h personal PM(2.5) exposures were measured. Data were used to identify significant factors affecting personal exposures and to develop 1-h personal exposure models for five different micro-environments. By incorporating the time-activity diary data, these models were then combined to develop a time-weighted microenvironmental personal model (model M1AD) to predict the 24-h PM(2.5) exposures measured for individuals in the Older Adults Study. Twenty-four-hour time-weighted models were also developed using 1-h ambient PM(2.5) levels and time-activity data (model A1AD) or using 24-h ambient PM(2.5) levels and time-activity data (model A24AD). The performance of these three models was compared to that using 24-h ambient concentrations alone (model A24). Results showed that factors affecting 1-h personal PM(2.5) exposures included air conditioning status and the presence of environmental tobacco smoke (ETS) for indoor micro-environments, consistent with previous studies. ETS was identified as a significant contributor to measured 24-h personal PM(2.5) exposures. Staying in an ETS-exposed microenvironment for 1 h elevated 24-h personal PM(2.5) exposures by approximately 4 microg/m 3 on average. Cooking and washing activities were identified in the winter as significant contributors to 24-h personal exposures as well, increasing 24-h personal PM(2.5) exposures by about 4 and 5 microg/m 3 per hour of activity, respectively. The ability of 3 microenvironmental personal exposure models to estimate 24-h personal PM(2.5) exposures was generally comparable to and consistently greater than that of model A24. Results indicated that using time-activity data with 1-h exposure information, either as micro-environment-specific exposures (model M1AD) or as ambient concentrations (model A1AD), improves our ability to estimate 24-h personal PM(2.5) exposure over the model using 24-h averaged ambient levels alone (model A24). Model performance was higher in the summer than in the winter season. In addition, higher crude R(2) values were reported for subjects participating in both seasons, where the R(2) values equaled.53,.55,.46, and.38 for models M1AD, A1AD, A24AD, and A24, respectively. The low predictive ability of the microenvironmental exposure models in the winter might, in part, be attributed to the narrow dynamic range of personal PM(2.5) exposures.