Melissa N. Eliot

Short-term Changes in Ambient Particulate Matter and Risk of Stroke: A Systematic Review and Meta-analysis

Background Stroke is a leading cause of death and long‐term disability in the United States. There is a well‐documented association between ambient particulate matter air pollution (PM) and cardiovascular disease morbidity and mortality. Given the pathophysiologic mechanisms of these effects, short‐term elevations in PM may also increase the risk of ischemic and/or hemorrhagic stroke morbidity and mortality, but the evidence has not been systematically reviewed. Methods and Results We provide a comprehensive review of all observational human studies (January 1966 to January 2014) on the association between short‐term changes in ambient PM levels and cerebrovascular events. We also performed meta‐analyses to evaluate the evidence for an association between each PM size fraction (PM2.5, PM10, PM2.5‐10) and each outcome (total cerebrovascular disease, ischemic stroke/transient ischemic attack, hemorrhagic stroke) separately for mortality and hospital admission. We used a random‐effects model to estimate the summary percent change in relative risk of the outcome per 10‐μg/m3 increase in PM. Conclusions We found that PM2.5 and PM10 are associated with a 1.4% (95% CI 0.9% to 1.9%) and 0.5% (95% CI 0.3% to 0.7%) higher total cerebrovascular disease mortality, respectively, with evidence of inconsistent, nonsignificant associations for hospital admission for total cerebrovascular disease or ischemic or hemorrhagic stroke. Current limited evidence does not suggest an association between PM2.5‐10 and cerebrovascular mortality or morbidity. We discuss the potential sources of variability in results across studies, highlight some observations, and identify gaps in literature and make recommendations for future studies.

High-risk HPV types and head and neck cancer

Although HPV16 has been strongly implicated in oropharyngeal carcinogenesis, the role of other high‐risk HPV types in the etiology of head and neck cancer remains unclear. To date, few data exist addressing the nature of the association between antibodies to oncogenic proteins of non‐HPV16 HPVs in relation to head and neck cancer. We examined the relationship between multiple HPV types (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) and head and neck squamous cell carcinoma (HNSCC) in a large population‐based case–control study (1069 cases and 1107 controls). Serological measures for HPV types included antibodies to L1, E6 and/or E7. In a secondary analysis, we excluded HPV16 seropositive subjects to examine independent associations with other high‐risk HPVs. All analyses were adjusted for age, race, sex, education, smoking and alcohol consumption. Statistically significant associations were observed for HPV16, 18, 33 and 52 and risk of HNSCC after mutually adjusting for HPV types. Among HPV16 seronegative subjects, elevated risks of HNSCC were observed for HPV18 E6 (OR = 4.19, 95% CI = 1.26–14.0), HPV33 E6 (OR = 7.96, 95% CI = 1.56–40.5) and HPV52 E7 (OR = 3.40, 95% CI = 1.16–9.99). When examined by tumor type, associations with HPV18 and HPV33 remained statistically significant for oropharyngeal cancer, and HPV52 was associated with oral cancer. In addition, magnitude of associations for HNSCC increased markedly with increasing number of seropositive high‐risk HPV infections. High‐risk HPV types, other than HPV16, are likely to be involved in the etiology of HNSCC.

Ambient Air Pollution and Depressive Symptoms in Older Adults: Results from the MOBILIZE Boston Study

Background: Exposure to ambient air pollution, particularly from traffic, has been associated with adverse cognitive outcomes, but the association with depressive symptoms remains unclear. Objectives: We investigated the association between exposure to ambient air and traffic pollution and the presence of depressive symptoms among 732 Boston-area adults ≥ 65 years of age (78.1 ± 5.5 years, mean ± SD). Methods: We assessed depressive symptoms during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). We estimated residential distance to the nearest major roadway as a marker of long-term exposure to traffic pollution and assessed short-term exposure to ambient fine particulate matter (PM2.5), sulfates, black carbon (BC), ultrafine particles, and gaseous pollutants, averaged over the 2 weeks preceding each assessment. We used generalized estimating equations to estimate the odds ratio (OR) of a CESD-R score ≥ 16 associated with exposure, adjusting for potential confounders. In sensitivity analyses, we considered CESD-R score as a continuous outcome and mean annual residential BC as an alternate marker of long-term exposure to traffic pollution. Results: We found no evidence of a positive association between depressive symptoms and long-term exposure to traffic pollution or short-term changes in pollutant levels. For example, we found an OR of CESD-R score ≥ 16 of 0.67 (95% CI: 0.46, 0.98) per interquartile range (3.4 μg/m3) increase in PM2.5 over the 2 weeks preceding assessment. Conclusions: We found no evidence suggesting that ambient air pollution is associated with depressive symptoms among older adults living in a metropolitan area in attainment of current U.S. regulatory standards. Citation: Wang Y, Eliot MN, Koutrakis P, Gryparis A, Schwartz JD, Coull BA, Mittleman MA, Milberg WP, Lipsitz LA, Wellenius GA. 2014. Ambient air pollution and depressive symptoms in older adults: results from the MOBILIZE Boston Study. Environ Health Perspect 122:553–558; http://dx.doi.org/10.1289/ehp.1205909

Variability and predictors of urinary concentrations of phthalate metabolites during early childhood.

The variability and predictors of urinary concentrations of phthalate metabolites in preschool-aged children have not been thoroughly examined. Additionally, the impact of temporal changes in the use and restriction of phthalates in children’s products has not been assessed. Our objective was to identify demographic, behavioral, and temporal predictors of urinary phthalate metabolite concentrations in young children. Between 2004 and 2011, we collected up to five urine samples from each of 296 children participating in a prospective birth cohort during annual study visits at ages 1–5 years. We used linear mixed models to calculate intraclass correlation coefficients (ICCs), a measure of within-individual reproducibility, and identify demographic predictors of urinary phthalate metabolites. We used multivariable linear regression to examine cross-sectional relationships between food packaging or personal care product use and phthalate metabolites measured at age 5 years. Across annual measurements, monoethyl phthalate exhibited the least variation (ICC = 0.38), while di-2-ethylhexyl phthalate (ΣDEHP) metabolites exhibited the most variation (ICC = 0.09). Concentrations changed with age, suggesting age-related changes in phthalate exposure and perhaps metabolism. Our findings suggest that fast food consumption may be a source of butylbenzyl phthalate and di-isononyl phthalate (DiNP) exposure, and some personal care products may be sources of diethyl phthalate exposure. Concentrations of ΣDEHP metabolites decreased over the study period; however, concentrations of DiNP metabolites increased. This finding suggests that manufacturer practices and regulations, like the Consumer Product Safety Improvement Act of 2008, may decrease DEHP exposure, but additional work characterizing the nature and toxicity of replacements is critically needed.

Current and projected heat-related morbidity and mortality in Rhode Island

Background: Climate change is expected to cause increases in heat-related mortality, especially among the elderly and very young. However, additional studies are needed to clarify the effects of heat on morbidity across all age groups and across a wider range of temperatures. Objectives: We aimed to estimate the impact of current and projected future temperatures on morbidity and mortality in Rhode Island. Methods: We used Poisson regression models to estimate the association between daily maximum temperature and rates of all-cause and heat-related emergency department (ED) admissions and all-cause mortality. We then used downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5; a standardized set of climate change model simulations) projections to estimate the excess morbidity and mortality that would be observed if this population were exposed to the temperatures projected for 2046–2053 and 2092–2099 under two representative concentration pathways (RCP): RCP 8.5 and 4.5. Results: Between 2005 and 2012, an increase in maximum daily temperature from 75 to 85°F was associated with 1.3% and 23.9% higher rates of all-cause and heat-related ED visits, respectively. The corresponding effect estimate for all-cause mortality from 1999 through 2011 was 4.0%. The association with all-cause ED admissions was strongest for those < 18 or ≥ 65 years of age, whereas the association with heat-related ED admissions was most pronounced among 18- to 64-year-olds. If this Rhode Island population were exposed to temperatures projected under RCP 8.5 for 2092–2099, we estimate that there would be 1.2% (range, 0.6–1.6%) and 24.4% (range, 6.9–41.8%) more all-cause and heat-related ED admissions, respectively, and 1.6% (range, 0.8–2.1%) more deaths annually between April and October. Conclusions: With all other factors held constant, our findings suggest that the current population of Rhode Island would experience substantially higher morbidity and mortality if maximum daily temperatures increase further as projected. Citation: Kingsley SL, Eliot MN, Gold J, Vanderslice RR, Wellenius GA. 2016. Current and projected heat-related morbidity and mortality in Rhode Island. Environ Health Perspect 124:460–467; http://dx.doi.org/10.1289/ehp.1408826

Gastric Reflux Is an Independent Risk Factor for Laryngopharyngeal Carcinoma

Background: Gastric reflux can reach into the upper airway, inducing cellular damage in the epithelial lining. This condition is believed to be a risk factor for development of laryngopharyngeal squamous cell carcinoma (LPSCC), although the literature is conflicting. Methods: To better clarify this relationship, we assessed the association of self-reported heartburn history and medication use among 631 patients with LPSCCs and 1234 control subjects (frequency-matched on age, gender, and town of residence) enrolled as part of a population-based case–control study of head and neck squamous cell carcinoma in the greater Boston area. Results: After adjusting for age, gender, race, smoking, alcohol consumption, HPV16 seropositivity, education, and body mass index, subjects reporting a history of frequent heartburn and who were neither a heavy smoker nor heavy drinker had a significantly elevated risk of LPSCCs [OR, 1.78; 95% confidence interval (CI), 1.00–3.16]. Among those with a history of heartburn, there was an inverse association between antacid use and LPSCCs relative to those never taking heartburn medication (OR, 0.59; 95% CI, 0.38–0.93) that remained consistent when analyzed by smoking/drinking status, HPV16 status, or by primary tumor site. Conclusions: Our data show that gastric reflux is an independent risk factor for squamous cancers of the pharynx and larynx. Further studies are needed to clarify the possible chemopreventive role of antacid use for patients with gastric reflux. Impact: Elucidation of additional risk factors for head and neck cancer can allow for risk stratification and inform surveillance of high-risk patients. Cancer Epidemiol Biomarkers Prev; 22(6); 1061–8. ©2013 AACR.

Smokeless tobacco and risk of head and neck cancer: evidence from a case-control study in New England.

Current studies suggesting that smokeless tobacco use increases the risk of head and neck cancer are hampered by small numbers. Consequently, there remains uncertainty in the magnitude and significance of this risk. We examined the relationship between smokeless tobacco use and head and neck squamous cell carcinoma (HNSCC) in a population‐based case–control study with 1,046 cases and 1,239 frequency‐matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for age, gender, race, education level, cigarette smoking, and alcohol consumption. A nonsignificant elevated association between having ever used smokeless tobacco and HNSCC risk (OR = 1.20, 95% CI: 0.67–2.16) was observed. Individuals who reported 10 or more years of smokeless tobacco use had a significantly elevated risk of HNSCC (OR = 4.06, 95% CI: 1.31–12.64), compared to never users. In an analysis restricted to never cigarette smokers, a statistically significant association was observed between ever use of smokeless tobacco and the risk of HNSCC (OR = 4.21, 95% CI: 1.01–17.57). These findings suggest that long‐term use of smokeless tobacco increases the risk of HNSCC.

RESIDENTIAL PROXIMITY TO MAJOR ROADWAYS AND INCIDENT HYPERTENSION IN POST-MENOPAUSAL WOMEN

Living near major roadways has been associated with increased risk of cardiovascular morbidity and mortality, presumably from exposure to elevated levels of traffic-related air and/or noise pollution. This association may potentially be mediated through increased risk of incident hypertension, but results from prior studies are equivocal. Using Cox proportional hazards models we examined residential proximity to major roadways and incident hypertension among 38,360 participants of the Womens Health Initiative (WHI) Clinical Trial cohorts free of hypertension at enrollment and followed for a median of 7.9 years. Adjusting for participant demographics and lifestyle, trial participation, and markers of individual and neighborhood socioeconomic status, the hazard ratios for incident hypertension were 1.13 (95% CI: 1.00, 1.28), 1.03 (0.95, 1.11), 1.05 (0.99, 1.11), and 1.05 (1.00, 1.10) for participants living ≤50, >50-200, >200-400, and >400-1000 m vs >1000 m from the nearest major roadway, respectively (ptrend=0.013). This association varied substantially by WHI study region with hazard ratios for women living ≤50 m from a major roadway of 1.61 (1.18, 2.20) in the West, 1.51 (1.22, 1.87) in the Northeast, 0.89 (0.70, 1.14) in the South, and 0.94 (0.75, 1.19) in the Midwest. In this large, national cohort of post-menopausal women, residential proximity to major roadways was associated with incident hypertension in selected regions of the U.S. If causal, these results suggest residential proximity to major roadways, as a marker for air, noise and other traffic-related pollution, may be a risk factor for hypertension.

Residential Proximity to Major Roadways and Prevalent Hypertension Among Postmenopausal Women: Results From the Women's Health Initiative San Diego Cohort

Background Living near major roadways has been linked with increased risk of cardiovascular events and worse prognosis. Residential proximity to major roadways may also be associated with increased risk of hypertension, but few studies have evaluated this hypothesis. Methods and Results We examined the cross‐sectional association between residential proximity to major roadways and prevalent hypertension among 5401 postmenopausal women enrolled into the San Diego cohort of the Womens Health Initiative. We used modified Poisson regression with robust error variance to estimate the association between prevalence of hypertension and residential distance to nearest major roadway, adjusting for participant demographics, medical history, indicators of individual and neighborhood socioeconomic status, and for local supermarket/grocery and fast food/convenience store density. The adjusted prevalence ratios for hypertension were 1.22 (95% CI: 1.07, 1.39), 1.13 (1.00, 1.27), and 1.05 (0.99, 1.12) for women living ≤100, >100 to 200, and >200 to 1000 versus >1000 m from a major roadway (P for trend=0.006). In a model treating the natural log of distance to major roadway as a continuous variable, a shift in distance from 1000 to 100 m from a major roadway was associated with a 9% (3%, 16%) higher prevalence of hypertension. Conclusions In this cohort of postmenopausal women, residential proximity to major roadways was positively associated with the prevalence of hypertension. If causal, these results suggest that living close to major roadways may be an important novel risk factor for hypertension.

Patterns, Variability, and Predictors of Urinary Bisphenol A Concentrations during Childhood

We examined the patterns, variability, and predictors of urinary bisphenol A (BPA) concentrations in 337 children from the Cincinnati, Ohio HOME Study. From 2003 to 2014, we collected two urine samples from women at 16 and 26 weeks of pregnancy and six urine samples from children at 1-5 and 8 years of age. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) as a measure of within-person BPA variability and to identify sociodemographic and environmental predictors. For the 8-year visit, we used multivariable linear regression to explore associations between urinary BPA concentrations and exposure-related factors. We calculated daily intakes using equations estimating creatinine excretion rates and creatinine-standardized BPA concentrations. Urinary BPA concentrations, which decreased over childhood, had a low degree of reproducibility (ICC < 0.2). Estimated daily intakes decreased with age and were below the reference dose of 50 μg/kg body weight/day. BPA concentrations were positively associated with consuming food stored or heated in plastic, consuming canned food and beverages, and handling cash register receipts. Our results suggest that there are multiple sources of BPA exposure in young children. Etiological studies should collect serial urine samples to accurately classify BPA exposure and consider sociodemographic and environmental factors as possible confounders.