Regional and racial/ethnic inequalities in public drinking water fluoride concentrations across the US.

BACKGROUND: Although the US Centers for Disease Control and Prevention (CDC) considers fluoridation of community water systems (CWSs) to be a major public health achievement responsible for reducing dental disease, recent epidemiologic evidence suggests that chronic exposure to population-relevant levels of fluoride may also be associated with adverse child neurodevelopmental outcomes. To our knowledge, a nationally representative database of CWS fluoride concentration estimates that can be readily linked to US epidemiologic cohorts for further study is not publicly available. Our objectives were to evaluate broad regional and sociodemographic inequalities in CWS fluoride concentrations across the US, and to determine if county-level racial/ethnic composition was associated with county-level CWS fluoride. METHODS: We generated CWS-level (N = 32,495) and population weighted county-level (N = 2152) fluoride concentration estimates using over 250,000 routine compliance monitoring records collected from the US Environmental Protection Agency's (EPA) Third Six Year Review (2006-2011). We compared CWS-level fluoride distributions across subgroups including region, population size served, and county sociodemographic characteristics. In county-level spatial error models, we also evaluated geometric mean ratios (GMRs) of CWS fluoride per 10% higher proportion of residents belonging to a given racial/ethnic subgroup. RESULTS: 4.5% of CWSs (serving >2.9 million residents) reported mean 2006-2011 fluoride concentrations ≥1500 µg/L (the World Health Organization's guideline for drinking water quality). Arithmetic mean, 90th, and 95th percentile contaminant concentrations were greatest in CWSs reliant on groundwater, located in the Southwest and Eastern Midwest, and serving Semi-Urban, Hispanic communities. In fully adjusted spatial error models, the GMR (95% CI) of CWS fluoride per a 10% higher proportion of county residents that were Hispanic/Latino was 1.16 (1.10, 1.23). IMPACT STATEMENT: We find that over 2.9 million US residents are served by public water systems with average fluoride concentrations exceeding the World Health Organization's guidance limit. We also find significant inequalities in community water system fluoride concentration estimates (2006-2011) across the US, especially for Hispanic/Latino communities who also experience elevated arsenic and uranium in regulated public drinking water systems. Our fluoride estimates can be leveraged in future epidemiologic studies to assess the potential association between chronic fluoride exposure and related adverse outcomes.

Incident dementia and long-term exposure to constituents of fine particle air pollution: A national cohort study in the United States.

Growing evidence suggests that fine particulate matter (PM2.5) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+), and soil dust (DUST). To investigate the impact of long-term exposure to PM2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM2.5 and its major constituents. An interquartile range increase in PM2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM2.5 constituents, associations remained significant for BC, OM, SO42-, and NH4+ for both end points (even after adjustments of other constituents), among which BC and SO42- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM2.5 is significantly associated with higher rates of incident dementia and AD and that SO42-, BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

Low-Concentration Air Pollution and Mortality in American Older Adults: A National Cohort Analysis (2001-2017).

Mounting epidemiological evidence has documented the associations between long-term exposure to multiple air pollutants and increased mortality. There is a pressing need to determine whether risks persist at low concentrations including below current national standards. Air pollution levels have decreased in the United States, and better understanding of the health effects of low-level air pollution is essential for the amendment of National Ambient Air Quality Standards (NAAQS). A nationwide, population-based, open cohort study was conducted to estimate the association between long-term exposure to low-level PM2.5, NO2, O3, and all-cause mortality. The study population included all Medicare enrollees (ages 65 years or older) in the contiguous U.S. from 2001 to 2017. We further defined three low-exposure subcohorts comprised of Medicare enrollees who were always exposed to low-level PM2.5 (annual mean ≤12-µg/m3), NO2 (annual mean ≤53-ppb), and O3 (warm-season mean ≤50-ppb), respectively, over the study period. Of the 68.7-million Medicare enrollees, 33.1% (22.8-million, mean age 75.9 years), 93.8% (64.5-million, mean age 76.2 years), and 65.0% (44.7-million, mean age 75.6 years) were always exposed to low-level annual PM2.5, annual NO2, and warm-season O3 over the study period, respectively. Among the low-exposure cohorts, a 10-µg/m3 increase in PM2.5, 10-ppb increase in NO2, and 10-ppb increase in warm-season O3, were, respectively, associated with an increase in mortality rate ranging between 10 and 13%, 2 and 4%, and 12 and 14% in single-pollutant models, and between 6 and 8%, 1 and 3%, and 9 and 11% in tripollutant models, using three statistical approaches. There was strong evidence of linearity in concentration-response relationships for PM2.5 and NO2 at levels below the current NAAQS, suggesting that no safe threshold exists for health-harmful pollution levels. For O3, the concentration-response relationship shows an increasingly positive association at levels above 40-ppb. In conclusion, exposure to low levels of PM2.5, NO2, and warm-season O3 was associated with an increased risk of all-cause mortality.

Assessment of metabolic perturbations associated with exposure to phthalates among pregnant African American women.

BACKGROUND: Phthalates have been linked with numerous harmful health effects. Limited data are available on the molecular mechanism underlying phthalate toxicity on human health. In this study, we measured urinary phthalate metabolites and used high-resolution metabolomics (HRM) to identify biological perturbations associated with phthalate exposures among pregnant African American (AA) women, who are disproportionately exposed to high phthalates levels. METHODS: We used untargeted HRM profiling to characterize serum samples collected during early (8-14 weeks gestation) and late (24-30 weeks gestation) pregnancy from 73 participants from the Atlanta AA Maternal-Child cohort. We measured eight urinary phthalate metabolites in early and late pregnancy, including Monoethyl phthalate (MEP), Mono(2-ethlyhexyl) phthalate (MEHP), and Mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), to assess maternal exposures to phthalates. Metabolite and metabolic pathway perturbation were evaluated using an untargeted HRM workflow. RESULTS: Geometric mean creatinine-adjusted levels of urinary MEP, MEHP, and MEHHP were 67.3, 1.4, and 4.1 µg/g creatinine, respectively, with MEP and MEHP higher than the mean levels of non-Hispanic blacks in the general US population (2015-2016). There were 73 and 1435 metabolic features significantly associated with at least one phthalate metabolite during early and late pregnancy (p < 0.005), respectively. Pathway enrichment analysis revealed perturbations in four inflammation- and oxidative-stress-related pathways associated with phthalate metabolite levels during both early and late pregnancy, including glycerophospholipid, urea cycle, arginine, and tyrosine metabolism. We confirmed 10 metabolites with level-1 evidence, which are associated with urinary phthalates, including thyroxine and thiamine, which were negatively associated with MEP, as well as tyramine and phenethylamine, which were positively associated with MEHP and MEHHP. CONCLUSION: Our results demonstrated that urinary phthalate levels were associated with perturbations in biological pathways connected with inflammation, oxidative stress, and endocrine disruption. The findings support future targeted investigations on molecular mechanisms underlying the impact of maternal phthalates exposure on adverse health outcomes.

Long-Term Exposure to Low-Level NO2 and Mortality among the Elderly Population in the Southeastern United States.

BACKGROUND: Mounting evidence has shown that long-term exposure to fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] and ozone (O3) can increase mortality. However, the health effects associated with long-term exposure to nitrogen dioxide (NO2) are less clear, in particular the evidence is scarce for NO2 at low levels that are below the current international guidelines. METHODS: We constructed a population-based full cohort comprising all Medicare beneficiaries (aged ≥65, N=13,590,387) in the southeastern United States from 2000 to 2016, and we then further defined the below-guideline cohort that included only those who were always exposed to low-level NO2, that is, with annual means below the current World Health Organization guidelines (i.e., ≤21 ppb). We applied previously estimated spatially and temporally resolved NO2 concentrations and assigned annual means to study participants based on their ZIP code of residence. Cox proportional hazards models were used to examine the association between long-term exposure to low-level NO2 and all-cause mortality, adjusting for potential confounders. RESULTS: About 71.1% of the Medicare beneficiaries in the southeastern United States were always exposed to low-level NO2 over the study period. We observed an association between long-term exposure to low-level NO2 and all-cause mortality, with a hazard ratio (HR)= 1.042 (95% CI: 1.040, 1.045) in single-pollutant models and a HR= 1.047 (95% CI: 1.045, 1.049) in multipollutant models (adjusting for PM2.5 and O3), per 10-ppb increase in annual NO2 concentrations. The penalized spline indicates a linear exposure-response relationship across the entire NO2 exposure range. Medicare enrollees who were White, female, and residing in urban areas were more vulnerable to long-term NO2 exposure. CONCLUSION: Using a large and representative cohort, we provide epidemiological evidence that long-term exposure to NO2, even below the national and global ambient air quality guidelines, was approximately linearly associated with a higher risk of mortality among older adults, independent of PM2.5 and O3 exposure. Improving air quality by reducing NO2 emissions, therefore, may yield significant health benefits. https://doi.org/10.1289/EHP9044.

Characterizing outdoor infiltration and indoor contribution of PM2.5 with citizen-based low-cost monitoring data.

Epidemiological research on the adverse health outcomes due to PM2.5 exposure frequently relies on measurements from regulatory air quality monitors to provide ambient exposure estimates, whereas personal PM2.5 exposure may deviate from ambient concentrations due to outdoor infiltration and contributions from indoor sources. Research in quantifying infiltration factors (Finf), the fraction of outdoor PM2.5 that infiltrates indoors, has been historically limited in space and time due to the high costs of monitor deployment and maintenance. Recently, the growth of openly accessible, citizen-based PM2.5 measurements provides an unprecedented opportunity to characterize Finf at large spatiotemporal scales. In this analysis, 91 consumer-grade PurpleAir indoor/outdoor monitor pairs were identified in California (41 residential houses and 50 public/commercial buildings) during a 20-month period with around 650000 h of paired PM2.5 measurements. An empirical method was developed based on local polynomial regression to estimate site-specific Finf. The estimated site-specific Finf had a mean of 0.26 (25th, 75th percentiles: [0.15, 0.34]) with a mean bootstrap standard deviation of 0.04. The Finf estimates were toward the lower end of those reported previously. A threshold of ambient PM2.5 concentration, approximately 30 µg/m3, below which indoor sources contributed substantially to personal exposures, was also identified. The quantified relationship between indoor source contributions and ambient PM2.5 concentrations could serve as a metric of exposure errors when using outdoor monitors as an exposure proxy (without considering indoor-generated PM2.5), which may be of interest to epidemiological research. The proposed method can be generalized to larger geographical areas to better quantify PM2.5 outdoor infiltration and personal exposure.

Air Pollutant Exposure and Stove Use Assessment Methods for the Household Air Pollution Intervention Network (HAPIN) Trial.

BACKGROUND: High quality personal exposure data is fundamental to understanding the health implications of household energy interventions, interpreting analyses across assigned study arms, and characterizing exposure-response relationships for household air pollution. This paper describes the exposure data collection for the Household Air Pollution Intervention Network (HAPIN), a multicountry randomized controlled trial of liquefied petroleum gas stoves and fuel among 3,200 households in India, Rwanda, Guatemala, and Peru. OBJECTIVES: The primary objectives of the exposure assessment are to estimate the exposure contrast achieved following a clean fuel intervention and to provide data for analyses of exposure-response relationships across a range of personal exposures. METHODS: Exposure measurements are being conducted over the 3-y time frame of the field study. We are measuring fine particulate matter [PM < 2.5µm in aerodynamic diameter (PM2.5)] with the Enhanced Children's MicroPEM™ (RTI International), carbon monoxide (CO) with the USB-EL-CO (Lascar Electronics), and black carbon with the OT21 transmissometer (Magee Scientific) in pregnant women, adult women, and children <1 year of age, primarily via multiple 24-h personal assessments (three, six, and three measurements, respectively) over the course of the 18-month follow-up period using lightweight monitors. For children we are using an indirect measurement approach, combining data from area monitors and locator devices worn by the child. For a subsample (up to 10%) of the study population, we are doubling the frequency of measurements in order to estimate the accuracy of subject-specific typical exposure estimates. In addition, we are conducting ambient air monitoring to help characterize potential contributions of PM2.5 exposure from background concentration. Stove use monitors (Geocene) are being used to assess compliance with the intervention, given that stove stacking (use of traditional stoves in addition to the intervention gas stove) may occur. CONCLUSIONS: The tools and approaches being used for HAPIN to estimate personal exposures build on previous efforts and take advantage of new technologies. In addition to providing key personal exposure data for this study, we hope the application and learnings from our exposure assessment will help inform future efforts to characterize exposure to household air pollution and for other contexts. https://doi.org/10.1289/EHP6422.

Sex differences in the interaction of short-term particulate matter exposure and psychosocial stressors on C-reactive protein in a Puerto Rican cohort.

There is substantial evidence linking particulate matter air pollution with cardiovascular morbidity and mortality. However, health disparities between populations may exist due to imprecisely defined non-innate susceptibility factors. Psychosocial stressors are associated with cardiovascular disease and may increase non-innate susceptibility to air-pollution. We investigated whether the association between short-term changes in ambient particulate matter and cardiovascular health risk differed by psychosocial stressors in a Puerto Rican cohort, comparing women and men. We used data from the Boston Puerto Rican Health Study (BPRHS), a longitudinal study of cardiovascular health among adults, collected between 2004 and 2013. We used mixed effect models to estimate the association of current-day ambient particle number concentration (PNC) on C-reactive protein (CRP), a marker of systemic inflammation, and effect modification by psychosocial stressors (depression, acculturation, perceived stress, discrimination, negative life events and a composite score). Point estimates of percent difference in CRP per interquartile range change in PNC varied among women with contrasting levels of stressors: negative life events (15.7% high vs. 6.5% low), depression score (10.6% high vs. 4.6% low) and composite stress score (16.2% high vs. 7.0% low). There were minimal differences among men. For Puerto Rican adults, cardiovascular non-innate susceptibility to adverse effects of ambient particles may be greater for women under high stress. This work contributes to understanding health disparities among minority ethnic populations.

Errors associated with the use of roadside monitoring in the estimation of acute traffic pollutant-related health effects.

Near-road monitoring creates opportunities to provide direct measurement on traffic-related air pollutants and to better understand the changing near-road environment. However, how such observations represent traffic-related air pollution exposures for estimating adverse health effect in epidemiologic studies remains unknown. A better understanding of potential exposure measurement error when utilizing near-road measurement is needed for the design and interpretation of the many observational studies linking traffic pollution and adverse health. The Dorm Room Inhalation to Vehicle Emission (DRIVE) study conducted near-road measurements of several single traffic indicators at six indoor and outdoor sites ranging from 0.01 to 2.3 km away from a heavily-trafficked (average annual daily traffic over 350,000) highway artery between September 2014 to January 2015. We examined spatiotemporal variability trends and assessed the potential for bias and errors when using a roadside monitor as a primary traffic pollution exposure surrogate, in lieu of more spatially-refined, proximal exposure indicators. Pollutant levels measured during DRIVE showed a low impact of this highway hotspot source. Primary pollutant species, including NO, CO, and BC declined to near background levels by 20-30 m from the highway source. Patterns of correlation among the sites also varied by pollutant and time of day. NO2, specifically, exhibited spatial trends that differed from other single-pollutant primary traffic indicators. This finding provides some indication of limitations in the use of NO2 as a primary traffic exposure indicator in panel-based health effect studies. Interestingly, roadside monitoring of NO, CO, and BC tended to be more strongly correlated with sites, both near and far from the road, during morning rush hour periods, and more weakly correlated during other periods of the day. We found pronounced attenuation of observed changes in health effects when using measured pollutant from the near-road monitor as a surrogate for true exposure, and the magnitude varied substantially over the course of the day. Caution should be taken when using near-road monitoring network observations, alone, to investigate health effects of traffic pollutants.

Air pollution, cardiovascular endpoints and susceptibility by stress and material resources: a systematic review of the evidence.

BACKGROUND AND METHODS: Evidence shows that both the physical and social environments play a role in the development of cardiovascular disease. The purpose of this systematic review is two-fold: First, we summarize research from the past 12 years from the growing number of studies focused on effect modification of the relationships between air pollution and cardiovascular disease (CVD) outcomes by socioeconomic position (SEP) and; second, we identify research gaps throughout the published literature on this topic and opportunities for addressing these gaps in future study designs. RESULTS: We identified 30 articles that examined the modifying effects of either material resources or psychosocial stress (both related to SEP) on associations between short and long-term air pollution exposure and CVD endpoints. Although 18 articles identified at least one interaction between an air pollutant and material resource indicator, 11 others did not. Support for susceptibility to air pollution by psychosocial stress was weaker; however, only three articles tested this hypothesis. Further studies are warranted to investigate how air pollution and SEP together may influence CVD. CONCLUSIONS: We recommend that such research include thorough assessment of air pollution and SEP correlations, including spatial correlation; investigate air pollution indices or multi-pollutant models; use standardized metrics of SEP to enhance comparability across studies; and evaluate potentially susceptible populations.

Development and evaluation of alternative approaches for exposure assessment of multiple air pollutants in Atlanta, Georgia.

Measurements from central site (CS) monitors are often used as estimates of exposure in air pollution epidemiological studies. As these measurements are typically limited in their spatiotemporal resolution, true exposure variability within a population is often obscured, leading to potential measurement errors. To fully examine this limitation, we developed a set of alternative daily exposure metrics for each of the 169 ZIP codes in the Atlanta, GA, metropolitan area, from 1999 to 2002, for PM(2.5) and its components (elemental carbon (EC), SO(4)), O(3), carbon monoxide (CO), and nitrogen oxides (NOx). Metrics were applied in a study investigating the respiratory health effects of these pollutants. The metrics included: (i) CS measurements (one CS per pollutant); (ii) air quality model results for regional background pollution; (iii) local-scale AERMOD air quality model results; (iv) hybrid air quality model estimates (a combination of (ii) and (iii)); and (iv) population exposure model predictions (SHEDS and APEX). Differences in estimated spatial and temporal variability were compared by exposure metric and pollutant. Comparisons showed that: (i) both hybrid and exposure model estimates exhibited high spatial variability for traffic-related pollutants (CO, NO(x), and EC), but little spatial variability among ZIP code centroids for regional pollutants (PM(2.5), SO(4), and O(3)); (ii) for all pollutants except NO(x), temporal variability was consistent across metrics; (iii) daily hybrid-to-exposure model correlations were strong (r>0.82) for all pollutants, suggesting that when temporal variability of pollutant concentrations is of main interest in an epidemiological application, the use of estimates from either model may yield similar results; (iv) exposure models incorporating infiltration parameters, time-location-activity budgets, and other exposure factors affect the magnitude and spatiotemporal distribution of exposure, especially for local pollutants. The results of this analysis can inform the development of more appropriate exposure metrics for future epidemiological studies of the short-term effects of particulate and gaseous ambient pollutant exposure in a community.

The relationship between averaged sulfate exposures and concentrations: results from exposure assessment panel studies in four U.S. cities.

This analysis examines differences between measured ambient indoor, and personal sulfate concentrations across cities, seasons, and individuals to elucidate how these differences may impact PM2.5 exposure measurement error. Data were analyzed from four panel studies conducted in Atlanta, Baltimore, Boston, and Steubenville (OH). Among the study locations, 1912 person-days of personal sulfate data were collected over 396 days involving 245 individual sampling sessions. Long-term differences in ambient and personal levels averaged over time are examined. Differences between averaged ambient and personal sulfate among and within cities were observed, driven by between subject and city differences in sulfate infiltration, F(inf), from outdoors to indoors. Neglecting this source of variability in associations may introduce bias in studies examining long-term exposures and chronic health. Indoor sulfate was highly correlated with and similar in magnitude to personal sulfate, suggesting indoor PM monitoring may be another means of characterizing true exposure variability.

Panel discussion review: session 1--exposure assessment and related errors in air pollution epidemiologic studies.

Examining the validity of exposure metrics used in air pollution epidemiologic models has been a key focus of recent exposure assessment studies. The objective of this work has been, largely, to determine what a given exposure metric represents and to quantify and reduce any potential errors resulting from using these metrics in lieu of true exposure measurements. The current manuscript summarizes the presentations of the co-authors from a recent EPA workshop, held in December 2006, dealing with the role and contributions of exposure assessment in addressing these issues. Results are presented from US and Canadian exposure and pollutant measurement studies as well as theoretical simulations to investigate what both particulate and gaseous pollutant concentrations represent and the potential errors resulting from their use in air pollution epidemiologic studies. Quantifying the association between ambient pollutant concentrations and corresponding personal exposures has led to the concept of defining attenuation factors, or alpha. Specifically, characterizing pollutant-specific estimates for alpha was shown to be useful in developing regression calibration methods involving PM epidemiologic risk estimates. For some gaseous pollutants such as NO2 and SO2, the associations between ambient concentrations and personal exposures were shown to be complex and still poorly understood. Results from recent panel studies suggest that ambient NO2 measurements may, in some locations, be serving as surrogates to traffic pollutants, including traffic-related PM2.5, hopanes, steranes, and oxidized nitrogen compounds (rather than NO2).

The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans.

In 1998 Congress mandated expanded U.S. Environmental Protection Agency (U.S. EPA) health effects research on ambient air particulate matter (PM) and a National Research Council (NRC) committee to provide research oversight. The U.S. EPA currently supports intramural and extramural PM research, including five academically based PM centers. The PM centers in their first 2.5 years have initiated research directed at critical issues identified by the NRC committee, including collaborative activities, and sponsored scientific workshops in key research areas. Through these activities, there is a better understanding of PM health effects and scientific uncertainties. Future PM centers research will focus on long-term effects associated with chronic PM exposures. This report provides a synopsis of accomplishments to date, short-term goals (during the next 2.5 years) and longer-term goals. It consists of six sections: biological mechanisms, acute effects, chronic effects, dosimetry, exposure assessment, and the specific attributes of a coordinated PM centers program.