Person:

Coull, Brent

Background: Adverse birth outcomes such as low birth weight and premature birth have been previously linked with exposure to ambient air pollution. Most studies relied on a limited number of monitors in the region of interest, which can introduce exposure error or restrict the analysis to persons living near a monitor, which reduces sample size and generalizability and may create selection bias. Methods We evaluated the relationship between premature birth and birth weight with exposure to ambient particulate matter (PM2.5) levels during pregnancy in Massachusetts for a 9-year period (2000–2008). Building on a novel method we developed for predicting daily PM2.5 at the spatial resolution of a 10x10km grid across New-England, we estimated the average exposure during 30 and 90 days prior to birth as well as the full pregnancy period for each mother. We used linear and logistic mixed models to estimate the association between PM2.5 exposure and birth weight (among full term births) and PM2.5 exposure and preterm birth adjusting for infant sex, maternal age, maternal race, mean income, maternal education level, prenatal care, gestational age, maternal smoking, percent of open space near mothers residence, average traffic density and mothers health. Results: Birth weight was negatively associated with PM2.5 across all tested periods. For example, a 10 μg/m3 increase of PM2.5 exposure during the entire pregnancy was significantly associated with a decrease of 13.80 g [95% confidence interval (CI) = −21.10, -6.05] in birth weight after controlling for other factors, including traffic exposure. The odds ratio for a premature birth was 1.06 (95% confidence interval (CI) = 1.01–1.13) for each 10 μg/m3 increase of PM2.5 exposure during the entire pregnancy period. Conclusions: The presented study suggests that exposure to PM2.5 during the last month of pregnancy contributes to risks for lower birth weight and preterm birth in infants.

Background: Previous studies found effect modification of associations between traffic-related air pollution and cardiovascular outcomes by polymorphisms in the hemochromatosis gene (HFE). As traffic-related air pollution may impact cognition through effects on cardiovascular health or through mechanisms which may also influence cardiovascular outcomes, we hypothesized that HFE polymorphisms would also modify a previously observed association between traffic-related air pollution exposure and cognition in older men. Methods: We considered data from 628 participants of the VA Normative Aging Study. We estimated long term exposure to black carbon (BC), a marker of traffic related air pollution, using a spatio-temporal land use regression model. We assessed cognition using the Mini-Mental State Examination (MMSE), a test of global function, and performance on a battery of other tests, covering a wide range of domains. We investigated whether variants of HFE C282Y and H63D modified the association between BC and having a low MMSE score using logistic models with generalized estimating equations and multiplicative interaction terms. Similarly, we assessed whether HFE variants modified the association between BC and performance on the cognitive battery using linear mixed models with multiplicative interaction terms. Results: Our results suggest modification of the BC-cognition association by HFE C282Y, although the test of interaction did not achieve statistical significance. In multivariable-adjusted models, participants who lacked a HFE C282Y variant (CC) exhibited an adverse association between BC and total cognition z-score (beta for a doubling in BC concentration: -0.061, 95% CI: -0.115, -0.007), while we did not observe an association in participants with at least one variant genotype (CY or YY) (beta for a doubling in BC concentration: 0.073, 95% CI: -0.081, 0.228; p-value for interaction: 0.11). The pattern of association was similar for analyses considering performance on the Mini-Mental State Examination. There was little evidence to support effect modification of the BC-cognition association by the HFE H63D genotype. Conclusions: Our data suggest that older adults who lack an HFE C282Y variant may be more susceptible to an adverse effect of traffic-related air pollution exposure on cognition. This finding and the proposed biological mechanism require confirmation.

Background: The underlying mechanisms of the association between ambient temperature and cardiovascular morbidity and mortality are not well understood, particularly for daily temperature variability. We evaluated if daily mean temperature and standard deviation of temperature was associated with heart rate-corrected QT interval (QTc) duration, a marker of ventricular repolarization in a prospective cohort of older men. Methods: This longitudinal analysis included 487 older men participating in the VA Normative Aging Study with up to three visits between 2000–2008 (n = 743). We analyzed associations between QTc and moving averages (1–7, 14, 21, and 28 days) of the 24-hour mean and standard deviation of temperature as measured from a local weather monitor, and the 24-hour mean temperature estimated from a spatiotemporal prediction model, in time-varying linear mixed-effect regression. Effect modification by season, diabetes, coronary heart disease, obesity, and age was also evaluated. Results: Higher mean temperature as measured from the local monitor, and estimated from the prediction model, was associated with longer QTc at moving averages of 21 and 28 days. Increased 24-hr standard deviation of temperature was associated with longer QTc at moving averages from 4 and up to 28 days; a 1.9°C interquartile range increase in 4-day moving average standard deviation of temperature was associated with a 2.8 msec (95%CI: 0.4, 5.2) longer QTc. Associations between 24-hr standard deviation of temperature and QTc were stronger in colder months, and in participants with diabetes and coronary heart disease. Conclusion/Significance In this sample of older men, elevated mean temperature was associated with longer QTc, and increased variability of temperature was associated with longer QTc, particularly during colder months and among individuals with diabetes and coronary heart disease. These findings may offer insight of an important underlying mechanism of temperature-related cardiovascular morbidity and mortality in an older population.

Background: Many studies report significant associations between PM2.5 (particulate matter <2.5 micrometers) and hospital admissions. These studies mostly rely on a limited number of monitors which introduces exposure error, and excludes rural and suburban populations from locations where monitors are not available, reducing generalizability and potentially creating selection bias. Methods: Using prediction models developed by our group, daily PM2.5 exposure was estimated across the Mid-Atlantic (Washington D.C., and the states of Delaware, Maryland, New Jersey, Pennsylvania, Virginia, New York and West Virginia). We then investigated the short-term effects of PM2.5 exposures on emergency hospital admissions of the elderly in the Mid-Atlantic region.We performed case-crossover analysis for each admission type, matching on day of the week, month and year and defined the hazard period as lag01 (a moving average of day of admission exposure and previous day exposure). Results: We observed associations between short-term exposure to PM2.5 and hospitalization for all outcomes examined. For example, for every 10-µg/m3 increase in short-term PM 2.5 there was a 2.2% increase in respiratory diseases admissions (95% CI = 1.9 to 2.6), and a 0.78% increase in cardiovascular disease (CVD) admission rate (95% CI = 0.5 to 1.0). We found differences in risk for CVD admissions between people living in rural and urban areas. For every10-µg/m3 increase in PM 2.5 exposure in the ‘rural’ group there was a 1.0% increase (95% CI = 0.6 to 1.5), while for the ‘urban’ group the increase was 0.7% (95% CI = 0.4 to 1.0). Conclusions: Our findings showed that PM2.5 exposure was associated with hospital admissions for all respiratory, cardio vascular disease, stroke, ischemic heart disease and chronic obstructive pulmonary disease admissions. In addition, we demonstrate that our AOD (Aerosol Optical Depth) based exposure models can be successfully applied to epidemiological studies investigating the health effects of short-term exposures to PM2.5.

Air pollution has been associated with increased systemic inflammation markers. We developed a new pathway analysis approach to investigate whether gene variants within relevant pathways (oxidative stress, endothelial function, and metal processing) modified the association between particulate air pollution and fibrinogen, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Our study population consisted of 822 elderly participants of the Normative Aging Study (1999–2011). To investigate the role of biological mechanisms and to reduce the number of comparisons in the analysis, we created pathway-specific scores using gene variants related to each pathway. To select the most appropriate gene variants, we used the least absolute shrinkage and selection operator (Lasso) to relate independent outcomes representative of each pathway (8-hydroxydeoxyguanosine for oxidative stress, augmentation index for endothelial function, and patella lead for metal processing) to gene variants. A high genetic score corresponds to a higher allelic risk profile. We fit mixed-effects models to examine modification by the genetic score of the weekly air pollution association with the outcome. Among participants with higher genetic scores within the oxidative stress pathway, we observed significant associations between particle number and fibrinogen, while we did not find any association among participants with lower scores (pinteraction = 0.04). Compared to individuals with low genetic scores of metal processing gene variants, participants with higher scores had greater effects of particle number on fibrinogen (pinteraction = 0.12), CRP (pinteraction = 0.02), and ICAM-1 (pinteraction = 0.08). This two-stage penalization method is easy to implement and can be used for large-scale genetic applications.

Background: Short-term particulate air pollution exposure is associated with reduced heart rate variability (HRV), a risk factor for cardiovascular morbidity and mortality, in many studies. Associations with sub-chronic or long-term exposures, however, have been sparsely investigated. We evaluated the effect of fine particulate matter (PM2.5) and black carbon (BC) exposures on HRV in an elderly cohort: the Normative Aging Study. Methods: We measured power in high frequency (HF) and low frequency (LF), standard deviation of normal-to-normal intervals (SDNN), and the LF:HF ratio among participants from the Greater Boston area. Residential BC exposures for 540 men (1161 study visits, 2000–2011) were estimated using a spatio-temporal land use regression model, and residential PM2.5 exposures for 475 men (992 visits, 2003–2011) were modeled using a hybrid satellite based and land-use model. We evaluated associations between moving averages of sub-chronic (3–84 day) and long-term (1 year) pollutant exposure estimates and HRV parameters using linear mixed models. Results: One-standard deviation increases in sub-chronic, but not long-term, BC were associated with reduced HF, LF, and SDNN and an increased LF:HF ratio (e.g., 28 day BC: −2.3 % HF [95 % CI:−4.6, −0.02]). Sub-chronic and long-term PM2.5 showed evidence of relations to an increased LF and LF:HF ratio (e.g., 1 year PM: 21.0 % LF:HF [8.6, 34.8]), but not to HF or SDNN, though the effect estimates were very imprecise and mostly spanned the null. Conclusions: We observed some evidence of a relation between longer-term BC and PM2.5 exposures and changes in HRV in an elderly cohort. While previous studies focused on short-term air pollution exposures, our results suggest that longer-term exposures may influence cardiac autonomic function. Electronic supplementary material The online version of this article (doi:10.1186/s12940-015-0074-z) contains supplementary material, which is available to authorized users.

Background: Short‐term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community‐based studies have assessed this association. Methods and Results: Two thousand thirty‐five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998–2001) and urinary creatinine‐indexed 8‐epi‐prostaglandin F2α (8‐epi‐PGF 2α) at the seventh and eighth (2005–2008) examinations. We measured fine particulate matter (PM 2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1‐, 2‐, 3‐, 5‐, and 7‐day moving averages of each pollutant. Measured myeloperoxidase and 8‐epi‐PGF 2α were loge transformed. We used linear regression models and linear mixed‐effects models with random intercepts for myeloperoxidase and indexed 8‐epi‐PGF 2α, respectively. Models were adjusted for demographic variables, individual‐ and area‐level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM 2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2‐ to 7‐day moving averages of PM 2.5 and sulfate were consistently positively associated with 8‐epi‐PGF 2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Conclusions: Our community‐based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress.

Background: The cardiovascular effects of low‐level environmental radiation exposures are poorly understood. Although particulate matter (PM) has been linked to cardiovascular morbidity and mortality, and elevated blood pressure (BP), the properties promoting its toxicity remain uncertain. Addressing a knowledge gap, we evaluated whether BP increased with higher exposures to radioactive components of ambient PM, herein referred to as particle radioactivity (PR). Methods and Results: We performed a repeated‐measures analysis of 852 men to examine associations between PR exposure and BP using mixed‐effects regression models. As a surrogate for PR, we used gross β activity, measured by the US Environmental Protection Agency's radiation monitoring network. Higher PR exposure was associated with increases in both diastolic BP and systolic BP, for exposures from 1 to 28 days. An interquartile range increase in 28‐day PR exposure was associated with a 2.95–mm Hg increase in diastolic BP (95% confidence interval, 2.25–3.66; P<0.001) and a 3.94–mm Hg increase in systolic BP (95% confidence interval, 2.62–5.27; P<0.001). For models including both PR and PM ≤2.5 µm, the PR‐BP associations remained stable and significant. For models including PR and black carbon or PR and particle number, the PR‐BP associations were attenuated; however, they remained significant for many exposure durations. Conclusions: This is the first study to demonstrate the potential adverse effects of PR on both systolic and diastolic BPs. These were independent and similar in magnitude to those of PM ≤2.5 µm, black carbon, and particle number. Understanding the effects of particle‐bound radionuclide exposures on BP may have important implications for environmental and public health policy.

Background: Reduced fetal growth is associated with perinatal and later morbidity. Prenatal exposure to environmental pollutants is linked to reduced fetal growth at birth, but the impact of concomitant exposure to multiple pollutants is unclear. The purpose of this study was to examine interactions between early pregnancy exposure to cigarette smoke, traffic pollution, and select perfluoroalkyl substances (PFASs) on birth weight-for-gestational age (BW/GA). Methods: Among 1597 Project Viva mother-infant pairs, we assessed maternal cigarette smoking by questionnaire, traffic pollution at residential address by black carbon land use regression model, and plasma concentration of select PFASs in early pregnancy. We calculated sex-specific BW/GA z-scores, an index of fetal growth, from national reference data. We fit covariate-adjusted multi-pollutant linear regression models and examined interactions between exposures, using a likelihood-ratio test to identify a best-fit model. Results: Two hundred six (13%) mothers smoked during pregnancy. Mean [standard deviation (SD)] for black carbon was 0.8 (0.3) μg/m3, perfluorooctane sulfonate (PFOS) was 29.1 (16.5) ng/mL, and BW/GA z-score was 0.19 (0.96). In the best-fit model, BW/GA z-score was lower in infants of mothers exposed to greater black carbon [− 0.08 (95% CI: -0.15, − 0.01) per interquartile range (IQR)]. BW/GA z-score (95% CI) was also lower in infants of mothers who smoked [− 0.09 (− 0.23, 0.06)] or were exposed to greater PFOS [− 0.03 (− 0.07, 0.02) per IQR], although confidence intervals crossed the null. There were no interactions between exposures. In secondary analyses, instead of PFOS, we examined perfluorononanoate (PFNA) [mean (SD): 0.7 (0.4) ng/mL], a PFAS more closely linked to lower BW/GA in our cohort. The best-fit multi-pollutant model included positive two-way interactions between PFNA and both black carbon and smoking (p-interactions = 0.03). Conclusions: Concurrent prenatal exposures to maternal smoking, black carbon, and PFOS are additively associated with lower fetal growth, whereas PFNA may attenuate associations of smoking and black carbon with lower fetal growth. It is important to examine interactions between multiple exposures in relation to health outcomes, as effects may not always be additive and may shed light on biological pathways. Electronic supplementary material The online version of this article (10.1186/s12940-018-0363-4) contains supplementary material, which is available to authorized users.