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.

Preterm birth and PM2.5 in Puerto Rico: evidence from the PROTECT birth cohort.

BACKGROUND: Preterm birth (PTB, birth before 37 weeks of gestation) has been associated with adverse health outcomes across the lifespan. Evidence on the association between PTB and prenatal exposure to air pollutants is inconsistent, and is especially lacking for ethnic/racial minority populations. METHODS: We obtained data on maternal characteristics and behaviors and PTB and other birth outcomes for women participating in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort, who lived in municipalities located along the North Coast of Puerto Rico. We assessed pre-natal PM2.5 exposures for each infant based on the nearest US Environmental Protection Agency monitor. We estimated prenatal phthalate exposures as the geometric mean of urinary measurements obtained during pregnancy. We then examined the association between PM2.5 and PTB using modified Poisson regression and assessed modification of the association by phthalate exposure levels and sociodemographic factors such as maternal age and infant gender. RESULTS: Among 1092 singleton births, 9.1% of infants were born preterm and 92.9% of mothers had at least a high school education. Mothers had a mean (standard deviation) age of 26.9 (5.5) years and a median (range) of 2.0 (1.0-8.0) pregnancies. Nearly all women were Hispanic white, black, or mixed race. Median (range) prenatal PM2.5 concentrations were 6.0 (3.1-19.8) µ g/m3. Median (interquartile range) prenatal phthalate levels were 14.9 (8.9-26.0) and 14.5 (8.4-26.0), respectively, for di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP). An interquartile range increase in PM2.5 was associated with a 1.2% (95% CI 0.4, 2.1%) higher risk of PTB. There was little difference in PTB risk in strata of infant sex, mother's age, family income, history of adverse birth outcome, parity, and pre-pregnancy body mass index. Pregnancy urinary phthalate metabolite levels did not modify the PM2.5-PTB association. CONCLUSION: Among ethnic minority women in Puerto Rico, prenatal PM2.5 exposure is associated with a small but significant increase in risk of PTB.

Projected Changes in Temperature-related Morbidity and Mortality in Southern New England.

BACKGROUND: Climate change is expected to result in more heat-related, but potentially fewer cold-related, emergency department visits and deaths. The net effect of projected changes in temperature on morbidity and mortality remains incompletely understood. We estimated the change in temperature-related morbidity and mortality at two sites in southern New England, United States, through the end of the 21st century. METHODS: We used distributed lag Poisson regression models to estimate the present-day associations between daily mean temperature and all-cause emergency department visits and deaths in Rhode Island and in Boston, Massachusetts. We estimated the change in temperature-related visits and deaths in 2045-2054 and 2085-2094 (relative to 2001-2010) under two greenhouse gas emissions scenarios (RCP4.5 and RCP8.5) using downscaled projections from an ensemble of over 40 climate models, assuming all other factors remain constant. RESULTS: We observed U-shaped relationships between temperature and morbidity and mortality in Rhode Island, with minima at 10.9°C and 22.5°C, respectively. We estimated that, if this population were exposed to the future temperatures projected under RCP8.5 for 2085-2094, there would be 5,976 (95% eCI = 1,630, 11,379) more emergency department visits but 218 (95% eCI = -551, 43) fewer deaths annually. Results were similar in Boston and similar but less pronounced in the 2050s and under RCP4.5. CONCLUSIONS: We estimated that in the absence of further adaptation, if the current southern New England population were exposed to the higher temperatures projected for future decades, temperature-related emergency department visits would increase but temperature-related deaths would not.

Association of neighborhood greenness with self-perceived stress, depression and anxiety symptoms in older U.S adults.

BACKGROUND: Neighborhood environment, such as green vegetation, has been shown to play a role in coping with stress and mental ill health. Yet, epidemiological evidence of the association between greenness and mental health is inconsistent. METHODS: We examined whether living in green space is associated with self-perceived stress, depressive and anxiety symptoms in a nationally representative, longitudinal sample of community-dwelling older adults (N = 4118; aged 57-85 years) in the United States. We evaluated perceived stress, depression and anxiety symptoms using the Cohen's Perceived Stress Scale, the Center for Epidemiological Studies - Depression, and the Hospital Anxiety and Depression Scale - anxiety subscale, respectively. Greenness was assessed for each participant using the Normalized Difference Vegetation Index at 250-m resolution, as well as a buffer of 1000-m. We conducted longitudinal analyses to assess the associations between greenness and mental health upon adjusting for confounders (e.g., education), and to examine potential mediation and effect modification. RESULTS: An interquartile range (0.25 point) increase in contemporaneous greenness was significantly associated with 0.238 unit (95% CI: - 0.346, - 0.130) and 0.162 unit (95% CI: - 0.271, - 0.054) decrease in the perceived stress in base and multivariable models, respectively. The magnitude of the association was similar or even stronger when examining summer (- 0.161; 95% CI: - 0.295, - 0.027) and annual average of greenness (- 0.188; 95% CI: - 0.337, - 0.038), as well as greenness buffer of 1000-m. The greenness-stress association was partially mediated by physical activity (15.1% mediated), where increased greenness led to increased physical activity and less stress, and by history of respiratory diseases (- 3.8% mediated), where increased greenness led to increased respiratory disease and more stress. The association was also significantly modified by race, social support, physical function, socioeconomic status, and region. While greenness was not significantly associated with anxiety and depressive scores across all participants, significant inverse associations were found for Whites participants, and for individuals with higher socioeconomic status, who were physically active, as compared to their counterparts. CONCLUSION: We found a direct association of greenness with perceived stress among older adults, and an indirect association mediated through physical activity and respiratory disease history. Our study findings warrant further examination of the mediation and modification of the greenness-mental health association.

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.

Spatio-temporal modeling of particulate air pollution in the conterminous United States using geographic and meteorological predictors.

BACKGROUND: Exposure to atmospheric particulate matter (PM) remains an important public health concern, although it remains difficult to quantify accurately across large geographic areas with sufficiently high spatial resolution. Recent epidemiologic analyses have demonstrated the importance of spatially- and temporally-resolved exposure estimates, which show larger PM-mediated health effects as compared to nearest monitor or county-specific ambient concentrations. METHODS: We developed generalized additive mixed models that describe regional and small-scale spatial and temporal gradients (and corresponding uncertainties) in monthly mass concentrations of fine (PM2.5), inhalable (PM10), and coarse mode particle mass (PM(2.5-10)) for the conterminous United States (U.S.). These models expand our previously developed models for the Northeastern and Midwestern U.S. by virtue of their larger spatial domain, their inclusion of an additional 5 years of PM data to develop predictions through 2007, and their use of refined geographic covariates for population density and point-source PM emissions. Covariate selection and model validation were performed using 10-fold cross-validation (CV). RESULTS: The PM2.5 models had high predictive accuracy (CV R2=0.77 for both 1988-1998 and 1999-2007). While model performance remained strong, the predictive ability of models for PM10 (CV R2=0.58 for both 1988-1998 and 1999-2007) and PM(2.5-10) (CV R2=0.46 and 0.52 for 1988-1998 and 1999-2007, respectively) was somewhat lower. Regional variation was found in the effects of geographic and meteorological covariates. Models generally performed well in both urban and rural areas and across seasons, though predictive performance varied somewhat by region (CV R2=0.81, 0.81, 0.83, 0.72, 0.69, 0.50, and 0.60 for the Northeast, Midwest, Southeast, Southcentral, Southwest, Northwest, and Central Plains regions, respectively, for PM2.5 from 1999-2007). CONCLUSIONS: Our models provide estimates of monthly-average outdoor concentrations of PM2.5, PM10, and PM(2.5-10) with high spatial resolution and low bias. Thus, these models are suitable for estimating chronic exposures of populations living in the conterminous U.S. from 1988 to 2007.

Air pollution exposure is associated with rhinitis in older US adults via specific immune mechanisms.

BACKGROUND: Pathophysiology of rhinitis in older adults is largely unknown. We tested whether air pollution is associated with this condition and how immune mechanisms may play a role in this relationship. METHODS: We analyzed cross-sectional data from the National Social Life, Health, and Aging Project, a nationally representative study of older adults born between 1920 and 1947. Particulate matter ≤2.5 µm (PM2.5 ) air pollution exposure estimates were generated using validated spatiotemporal models. Presence of rhinitis was defined based on medication use (≥1: intranasal medications: steroids, antihistamines, lubricants, and/or decongestants, and/or oral medications: antihistamines and/or decongestants). K-means cluster analysis (Jaccard method) was used to group 13 peripheral blood cytokines into 3 clusters to facilitate functional determination. We fitted multivariate logistic regressions to correlate PM2.5 exposure with presence of rhinitis, controlling for confounders, and then determined the role of cytokines in this relationship. RESULTS: Long- (but not short-) term exposure to PM2.5 was associated with presence of rhinitis: 3-year exposure window, odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.98, 1.80, per 1 standard deviation (SD) PM2.5 increase. Inclusion of cytokine cluster in the model led to a modestly stronger effect of PM2.5 exposure on rhinitis (OR = 1.37; 95% CI: 1.00, 1.87; 3-year exposure window). The particular immune profile responsible for this result was composed of elevated IL-3, IL-12, and IFN-γ (OR = 4.86, 95% CI: 1.10, 21.58, immune profile-PM2.5 exposure interaction term). CONCLUSION: We show for the first time that IL-3, IL-12, and IFN-γ explain in part the relationship between PM2.5 exposure and rhinitis in older US adults. If confirmed, these immune pathways may be used as therapeutic targets.

The effect of primary organic particles on emergency hospital admissions among the elderly in 3 US cities.

BACKGROUND: Fine particle (PM2.5) pollution related to combustion sources has been linked to a variety of adverse health outcomes. Although poorly understood, it is possible that organic carbon (OC) species, particularly those from combustion-related sources, may be partially responsible for the observed toxicity of PM2.5. The toxicity of the OC species may be related to their chemical structures; however, few studies have examined the association of OC species with health impacts. METHODS: We categorized 58 primary organic compounds by their chemical properties into 5 groups: n-alkanes, hopanes, cyclohexanes, PAHs and isoalkanes. We examined their impacts on the rate of daily emergency hospital admissions among Medicare recipients in Atlanta, GA and Birmingham, AL (2006-2009), and Dallas, TX (2006-2007). We analyzed data in two stages; we applied a case-crossover analysis to simultaneously estimate effects of individual OC species on cause-specific hospital admissions. In the second stage we estimated the OC chemical group-specific effects, using a multivariate weighted regression. RESULTS: Exposures to cyclohexanes of six days and longer were significantly and consistently associated with increased rate of hospital admissions for CVD (3.40%, 95%CI = (0.64, 6.24%) for 7-d exposure). Similar increases were found for hospitalizations for ischemic heart disease and myocardial infarction. For respiratory related hospital admissions, associations with OC groups were less consistent, although exposure to iso-/anteiso-alkanes was associated with increased respiratory-related hospitalizations. CONCLUSIONS: Results suggest that week-long exposures to traffic-related, primary organic species are associated with increased rate of total and cause-specific CVD emergency hospital admissions. Associations were significant for cyclohexanes, but not hopanes, suggesting that chemical properties likely play an important role in primary OC toxicity.

Structural equation modeling of parasympathetic and sympathetic response to traffic air pollution in a repeated measures study.

BACKGROUND: Traffic-related air pollution has been associated to a range of adverse health impacts, including decreased heart rate variability (HRV). The association between traffic-related pollution and HRV, however, has varied by traffic-related or HRV marker as well as by study, suggesting the need for a more comprehensive and integrative approach to examining air pollution-mediated biological impacts on these outcomes. In a Bayesian framework, we examined the effect of traffic pollution on HRV using structural equation models (SEMs) and looked at effect modification by participant characteristics. METHODS: We studied measurements of 5 HRV markers [high frequency (HF), low frequency (LF), 5-min standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences of successive normal-to-normal intervals (rMSSD), and LF/HF ratio (LF/HF)] for 700 elderly men from the Normative Aging Study. Using SEMs, we fit a latent variable for traffic pollution that is reflected by levels of carbon monoxide, nitrogen monoxide, nitrogen dioxide, and black carbon (BC) to estimate its effect on latent variable for parasympathetic tone that included HF, SDNN and rMSSD, and the sympathetic tone marker, LF/HF. Exposure periods were assessed using 4-, 24-, 48-, 72-hour moving average pre-visit. We compared our main effect findings using SEMs with those obtained using linear mixed models. RESULTS: Traffic pollution was not associated with mean parasympathetic tone and LF/HF for all examined moving averages. In Bayesian linear mixed models, however, BC was related to increased LF/HF, an inter quartile range (IQR) increase in BC was associated with a 6.5% (95% posterior interval (PI): -0.7%, 14.2%) increase in mean LF/HF 24-hours later. The strongest association observed was for the 4-hour moving average (10.1%; 95% PI: 3.0%, 17.6%). The effect of traffic on parasympathetic tone was stronger among diabetic as compared to non-diabetic participants. Specifically, an IQR increase in traffic pollution in the 48-hr prior to the clinic visit was associated with a 44.3% (95% PI: -67.7%, -4.2%) lower mean parasympathetic tone among diabetics, and a 7.7% (95% PI: -18.0%, 41.4%) higher mean parasympathetic tone among non-diabetics. CONCLUSIONS: BC was associated with adverse changes LF/HF in the elderly. Traffic pollution may decrease parasympathetic tone among diabetic elderly.

Modeling the association between particle constituents of air pollution and health outcomes.

There is increasing interest in evaluating the association between specific fine-particle (particles with aerodynamic diameters less than 2.5 µm; PM2.5) constituents and adverse health outcomes rather than focusing solely on the impact of total PM2.5. Because PM2.5 may be related to both constituent concentration and health outcomes, constituents that are more strongly correlated with PM2.5 may appear more closely related to adverse health outcomes than other constituents even if they are not inherently more toxic. Therefore, it is important to properly account for potential confounding by PM2.5 in these analyses. Usually, confounding is due to a factor that is distinct from the exposure and outcome. However, because constituents are a component of PM2.5, standard covariate adjustment is not appropriate. Similar considerations apply to source-apportioned concentrations and studies assessing either short-term or long-term impacts of constituents. Using data on 18 constituents and data from 1,060 patients admitted to a Boston medical center with ischemic stroke in 2003-2008, the authors illustrate several options for modeling the association between constituents and health outcomes that account for the impact of PM2.5. Although the different methods yield results with different interpretations, the relative rankings of the association between constituents and ischemic stroke were fairly consistent across models.

Non-pharmaceutical interventions and COVID-19 cases in US summer camps: results from an American Camp Association survey.

BACKGROUND: Most camps remained closed during Summer 2020, due to concerns regarding child transmission of SARS-CoV-2 and limited information about the effectiveness of non-pharmaceutical interventions (NPIs) within child congregate settings. METHODS: We surveyed US camps about on-site operations, camper and staff demographics, COVID-19 cases among campers and staff, and NPI usage as related to pre-camp quarantine, facial coverings, physical distancing, cleaning and facility modifications. For all NPIs, save quarantine, responses were provided on a 5-point Likert scale format. RESULTS: Within 486 on-site camps, a range of NPIs were instituted, most often related to reduced camper interactions, staff face coverings, cleaning and hand hygiene. Camper facial coverings were less common, with campers always wearing masks at ~34% of the camps. Approximately 15% of camps reported 1+ confirmed COVID-19 case in either campers or staff, with three camps reporting a COVID-19 outbreak. In both single and multi-NPI analyses, the risk of COVID-19 cases was lowest when campers always wore facial coverings. Constant use of staff facial coverings and targeted physical distancing measures, but not pre-camp quarantine, also reduced COVID-19 risks. CONCLUSIONS: We found constant facial coverings, especially for campers, and targeted physical distancing measures to reduce risks of SARS-CoV-2 transmission within summer camps. Our findings provide valuable insights for future operations of summer camps and other child congregate settings regarding the use of NPIs to reduce the risk of SARS-CoV-2 infection.

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.

Particulate air pollution and socioeconomic position in rural and urban areas of the Northeastern United States.

OBJECTIVES: Although differential exposure by socioeconomic position (SEP) to hazardous waste and lead is well demonstrated, there is less evidence for particulate air pollution (PM), which is associated with risk of death and illness. This study determined the relationship of ambient PM and SEP across several spatial scales. METHODS: Geographic information system-based, spatio-temporal models were used to predict PM in the Northeastern United States. Predicted concentrations were related to census tract SEP and racial composition using generalized additive models. RESULTS: Lower SEP was associated with small, significant increases in PM. Annual PM(10) decreased between 0.09 and 0.93 micrograms per cubic meter and PM(2.5) between 0.02 and 0.94 micrograms per cubic meter for interquartile range increases in income. Decrements in PM with SEP increased with spatial scale, indicating that between-city spatial gradients were greater than within-city differences. The PM-SEP relation in urban tracts was not substantially modified by racial composition. CONCLUSIONS: Lower compared with higher SEP populations were exposed to higher ambient PM in the Northeastern United States. Given the small percentage change in annual PM(2.5) and PM(10), SEP was not likely a major source of confounding in epidemiological studies of PM, especially those conducted within a single urban/metropolitan area.

Non-nutritive suck and airborne metal exposures among Puerto Rican infants.

Air pollution has been shown to impact multiple measures of neurodevelopment in young children. Its effects on particularly vulnerable populations, such as ethnic minorities, however, is less studied. To address this gap in the literature, we assess the associations between infant non-nutritive suck (NNS), an early indicator of central nervous system integrity, and air pollution exposures in Puerto Rico. Among infants aged 0-3 months enrolled in the Center for Research on Early Childhood Exposure and Development (CRECE) cohort from 2017 to 2019, we examined associations between exposure to fine particulate matter (PM2.5) and its components on infant NNS in Puerto Rico. NNS was assessed using a pacifier attached to a pressure transducer, allowing for real-time visualization of NNS amplitude, frequency, duration, cycles/burst, cycles/min and bursts/min. These data were linked to 9-month average prenatal concentrations of PM2.5 and components, measured at three community monitoring sites. We used linear regression to examine the PM2.5-NNS association in single pollutant models, controlling for infant sex, maternal age, gestational age, and season of birth in base and additionally for household smoke exposure, age at testing, and NNS duration in full models. Among 198 infants, the average NNS amplitude and burst duration was 17.1 cmH2O and 6.1 s, respectively. Decreased NNS amplitude was consistently and significantly associated with 9-month average exposure to sulfur (-1.026 ± 0.507), zinc (-1.091 ± 0.503), copper (-1.096 ± 0.535) vanadium (-1.157 ± 0.537), and nickel (-1.530 ± 0.501). Decrements in NNS frequency were associated with sulfur exposure (0.036 ± 0.018), but not other examined PM components. Our findings provide new evidence that prenatal maternal exposure to specific PM components are associated with impaired neurodevelopment in Puerto Rican infants soon after birth.

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.

Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults.

OBJECTIVES: Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects. METHODS: 25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM(2.5)) and sulphate (SO(4)(2-)) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status. RESULTS: A 5.8 mg/l elevation in CRP was associated with decreases of between -8% and -33% for time and frequency domain HRV outcomes. A 5.1 microg/m(3) increase in SO(4)(2-) on the day before the health assessment was associated with a decrease of -6.7% in the SD of normal RR intervals (SDNN) (95% CI -11.8% to -1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM(2.5). CONCLUSIONS: Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation.

Rapid DNA methylation changes after exposure to traffic particles.

RATIONALE: Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis. OBJECTIVES: We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome. METHODS: We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction-pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter < or = 2.5 microm [PM2.5], or sulfate) in multiple time windows (4 h to 7 d) before the examination. We estimated standardized regression coefficients (beta) expressing the fraction of a standard deviation change in DNA methylation associated with a standard deviation increase in exposure. MEASUREMENTS AND MAIN RESULTS: Repetitive element DNA methylation varied in association with time-related variables, such as day of the week and season. LINE-1 methylation decreased after recent exposure to higher black carbon (beta = -0.11; 95% confidence interval [CI], -0.18 to -0.04; P = 0.002) and PM2.5 (beta = -0.13; 95% CI, -0.19 to -0.06; P < 0.001 for the 7-d moving average). In two-pollutant models, only black carbon, a tracer of traffic particles, was significantly associated with LINE-1 methylation (beta = -0.09; 95% CI, -0.17 to -0.01; P = 0.03). No association was found with Alu methylation (P > 0.12). CONCLUSIONS: We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined.

Hourly measurements of fine particulate sulfate and carbon aerosols at the Harvard-U.S. Environmental Protection Agency Supersite in Boston.

Hourly concentrations of ambient fine particle sulfate and carbonaceous aerosols (elemental carbon [EC], organic carbon [OC], and black carbon [BC]) were measured at the Harvard-U.S. Environmental Protection Agency Supersite in Boston, MA, between January 2007 and October 2008. These hourly concentrations were compared with those made using integrated filter-based measurements over 6-day or 24-hr periods. For sulfate, the two measurement methods showed good agreement. Semicontinuous measurements of EC and OC also agreed (but not as well as for sulfate) with those obtained using 24-hr integrated filter-based and optical BC reference methods. During the study period, 24-hr PM2.5 (particulate matter [PM] < or = 2.5 microm in aerodynamic diameter) concentrations ranged from 1.4 to 37.6 microg/m3, with an average of 9.3 microg/m3. Sulfate as the equivalent of ammonium sulfate accounted for 39.1% of the PM2.5 mass, whereas EC and OC accounted for 4.2 and 35.2%, respectively. Hourly sulfate concentrations showed no distinct diurnal pattern, whereas hourly EC and BC concentrations peaked during the morning rush hour between 7:00 and 9:00 a.m. OC concentrations also exhibited nonpronounced, small peaks during the day, most likely related to traffic, secondary organic aerosol, and local sources, respectively.

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.