Detection and analysis of endogenous polar volatile organic compounds (PVOCs) in urine for human exposome research.

Background: The human exposome, defined as '…everything that is not the genome', comprises all chemicals in the body interacting with life processes. The exposome drives genes x environment (GxE) interactions that can cause long-term latency and chronic diseases. The exposome constantly changes in response to external exposures and internal metabolism. Different types of compounds are found in different biological media. Objective: Measure polar volatile organic compounds (PVOCs) excreted in urine to document endogenous metabolites and exogenous compounds from environmental exposures. Methods: Use headspace collection and sorbent tube thermal desorption coupled with bench-top gas chromatography-mass spectrometry (GC-MS) for targeted and non-targeted approaches. Identify and categorize PVOCs that may distinguish among healthy and affected individuals. Results: Method is successfully demonstrated to tabulate a series of 28 PVOCs detected in human urine across 120 samples from 28 human subjects. Median concentrations range from below detect to 165 ng/mL. Certain PVOCs have potential health implications. Conclusions: Headspace collection with sorbent tubes is an effective method for documenting PVOCs in urine that are otherwise difficult to measure. This methodology can provide probative information regarding biochemical processes and adverse outcome pathways (AOPs) for toxicity testing.

Evaluation of individual and area-level factors as modifiers of the association between warm-season temperature and pediatric asthma morbidity in Atlanta, GA.

INTRODUCTION: Previous studies have found associations between respiratory morbidity and high temperatures; however, few studies have explored associations in potentially sensitive sub-populations. METHODS: We evaluated individual and area-level factors as modifiers of the association between warm-season (May-Sept.) temperature and pediatric respiratory morbidity in Atlanta. Emergency department (ED) visit data were obtained for children, 5-18 years old, with primary diagnoses of asthma or respiratory disease (diagnoses of upper respiratory infections, bronchiolitis, pneumonia, chronic obstructive pulmonary disease, asthma, or wheeze) in 20-county Atlanta during 1993-2012. Daily maximum temperature (Tmax) was acquired from the automated surface observing station at Atlanta Hartsfield International Airport. Poisson generalized linear models were used to estimate rate ratios (RR) between daily Tmax and asthma or respiratory disease ED visits, controlling for time and meteorology. Tmax effects were estimated for single-day lags of 0-6 days, for 3-, 5-, and 7-day moving averages and modeled with cubic terms to allow for non-linear relationships. Effect modification by individual factors (sex, race, insurance status) and area-level socioeconomic status (SES; ZIP code levels of poverty, education, and the neighborhood deprivation index) was examined via stratification. RESULTS: Estimated RRs for Tmax and pediatric asthma ED visits were positive and significant for lag days 1-5, with the strongest single day association observed on lag day 2 (RR=1.06, 95% CI: 1.03, 1.09) for a change in Tmax from 27°C to 32°C (25th to 75th percentile). For the moving average exposure periods, associations increased as moving average periods increased. We observed stronger RRs between Tmax and asthma among males compared to females, non-white children compared to white children, children with private insurance compared to children with Medicaid, and among children living in high compared to low SES areas. Associations between Tmax and respiratory disease ED visits were weak and non-significant (p-value>0.05). CONCLUSIONS: Results suggest socio-demographic factors (race/ethnicity, insurance status, and area-level SES) may confer vulnerability to temperature-related pediatric asthma morbidity. Our findings of weaker associations among children with Medicaid compared to other health insurance types and among children living in low compared to high SES areas run counter to our belief that children from disadvantaged households or ZIP codes would be more vulnerable to the respiratory effects of temperature. The potential reasons for these unexpected results are explored in the discussion.

Ozone and childhood respiratory disease in three US cities: evaluation of effect measure modification by neighborhood socioeconomic status using a Bayesian hierarchical approach.

BACKGROUND: Ground-level ozone is a potent airway irritant and a determinant of respiratory morbidity. Susceptibility to the health effects of ambient ozone may be influenced by both intrinsic and extrinsic factors, such as neighborhood socioeconomic status (SES). Questions remain regarding the manner and extent that factors such as SES influence ozone-related health effects, particularly across different study areas. METHODS: Using a 2-stage modeling approach we evaluated neighborhood SES as a modifier of ozone-related pediatric respiratory morbidity in Atlanta, Dallas, & St. Louis. We acquired multi-year data on emergency department (ED) visits among 5-18 year olds with a primary diagnosis of respiratory disease in each city. Daily concentrations of 8-h maximum ambient ozone were estimated for all ZIP Code Tabulation Areas (ZCTA) in each city by fusing observed concentration data from available network monitors with simulations from an emissions-based chemical transport model. In the first stage, we used conditional logistic regression to estimate ZCTA-specific odds ratios (OR) between ozone and respiratory ED visits, controlling for temporal trends and meteorology. In the second stage, we combined ZCTA-level estimates in a Bayesian hierarchical model to assess overall associations and effect modification by neighborhood SES considering categorical and continuous SES indicators (e.g., ZCTA-specific levels of poverty). We estimated ORs and 95% posterior intervals (PI) for a 25 ppb increase in ozone. RESULTS: The hierarchical model combined effect estimates from 179 ZCTAs in Atlanta, 205 ZCTAs in Dallas, and 151 ZCTAs in St. Louis. The strongest overall association of ozone and pediatric respiratory disease was in Atlanta (OR = 1.08, 95% PI: 1.06, 1.11), followed by Dallas (OR = 1.04, 95% PI: 1.01, 1.07) and St. Louis (OR = 1.03, 95% PI: 0.99, 1.07). Patterns of association across levels of neighborhood SES in each city suggested stronger ORs in low compared to high SES areas, with some evidence of non-linear effect modification. CONCLUSIONS: Results suggest that ozone is associated with pediatric respiratory morbidity in multiple US cities; neighborhood SES may modify this association in a non-linear manner. In each city, children living in low SES environments appear to be especially vulnerable given positive ORs and high underlying rates of respiratory morbidity.

A Case-Crossover Analysis of Indoor Heat Exposure on Mortality and Hospitalizations among the Elderly in Houston, Texas.

BACKGROUND: Despite the substantial role indoor exposure has played in heat wave-related mortality, few epidemiological studies have examined the health effects of exposure to indoor heat. As a result, knowledge gaps regarding indoor heat-health thresholds, vulnerability, and adaptive capacity persist. OBJECTIVE: We evaluated the role of indoor heat exposure on mortality and morbidity among the elderly (≥65 years of age) in Houston, Texas. METHODS: Mortality and emergency hospital admission data were obtained through the Texas Department of State Health Services. Summer indoor heat exposure was modeled at the U.S. Census block group (CBG) level using building energy models, outdoor weather data, and building characteristic data. Indoor heat-health associations were examined using time-stratified case-crossover models, controlling for temporal trends and meteorology, and matching on CBG of residence, year, month, and weekday of the adverse health event. Separate models were fitted for three indoor exposure metrics, for individual lag days 0-6, and for 3-d moving averages (lag 0-2). Effect measure modification was explored via stratification on individual- and area-level vulnerability factors. RESULTS: We estimated positive associations between short-term changes in indoor heat exposure and cause-specific mortality and morbidity [e.g., circulatory deaths, odds ratio per 5°C increase=1.16 (95% CI: 1.03, 1.30)]. Associations were generally positive for earlier lag periods and weaker across later lag periods. Stratified analyses suggest stronger associations between indoor heat and emergency hospital admissions among African Americans compared with Whites. DISCUSSION: Findings suggest excess mortality among certain elderly populations in Houston who are likely exposed to high indoor heat. We developed a novel methodology to estimate indoor heat exposure that can be adapted to other U.S. LOCATIONS: In locations with high air conditioning prevalence, simplified modeling approaches may adequately account for indoor heat exposure in vulnerable neighborhoods. Accounting for indoor heat exposure may improve the estimation of the total impact of heat on health. https://doi.org/10.1289/EHP6340.

Application of geostatistical approaches to predict the spatio-temporal distribution of summer ozone in Houston, Texas.

Mitigation of adverse effects of air pollution requires understanding underlying exposures, such as ambient ozone concentrations. Geostatistical approaches were employed to analyze temporal trends and estimate spatial patterns of summertime ozone concentrations for Houston, Texas, based on hourly ozone observations obtained from the Texas Commission on Environmental Quality. We systematically assess the accuracy of several spatial interpolation methods, comparing inverse distance weighting, simple kriging, ordinary kriging, and universal kriging methods utilizing the hourly ozone observations and meteorological measurements from monitoring sites. Model uncertainty was assessed by leave-one-out cross-validation. Kriging methods performed better, showing greater consistency in the generated surfaces, fewer interpolation errors, and lower biases. Universal kriging did not significantly improve the interpolation results compared to ordinary kriging, and thus ordinary kriging was determined to be the optimal method, striking a balance between accuracy and simplicity. The resulting spatial patterns indicate that the more industrialized areas east and northeast of Houston exhibit the highest summertime ozone concentrations. Estimated daily maximum 8 h ozone concentration fields generated will be used to inform research on population health risks from exposure to surface ozone in Houston.

Urban heat and air pollution: A framework for integrating population vulnerability and indoor exposure in health risk analyses.

Urban growth and climate change will exacerbate extreme heat events and air pollution, posing considerable health challenges to urban populations. Although epidemiological studies have shown associations between health outcomes and exposures to ambient air pollution and extreme heat, the degree to which indoor exposures and social and behavioral factors may confound or modify these observed effects remains underexplored. To address this knowledge gap, we explore the linkages between vulnerability science and epidemiological conceptualizations of risk to propose a conceptual and analytical framework for characterizing current and future health risks to air pollution and extreme heat, indoors and outdoors. Our framework offers guidance for research on climatic variability, population vulnerability, the built environment, and health effects by illustrating how health data, spatially resolved ambient data, estimates of indoor conditions, and household-level vulnerability data can be integrated into an epidemiological model. We also describe an approach for characterizing population adaptive capacity and indoor exposure for use in population-based epidemiological models. Our framework and methods represent novel resources for the evaluation of health risks from extreme heat and air pollution, both indoors and outdoors.

Assessment of neighbourhood-level socioeconomic status as a modifier of air pollution-asthma associations among children in Atlanta.

BACKGROUND: A broad literature base provides evidence of association between air pollution and paediatric asthma. Socioeconomic status (SES) may modify these associations; however, previous studies have found inconsistent evidence regarding the role of SES. METHODS: Effect modification of air pollution-paediatric asthma morbidity by multiple indicators of neighbourhood SES was examined in Atlanta, Georgia. Emergency department (ED) visit data were obtained for 5-18 years old with a diagnosis of asthma in 20-county Atlanta during 2002-2008. Daily ZIP Code Tabulation Area (ZCTA)-level concentrations of ozone, nitrogen dioxide, fine particulate matter and elemental carbon were estimated using ambient monitoring data and emissions-based chemical transport model simulations. Pollutant-asthma associations were estimated using a case-crossover approach, controlling for temporal trends and meteorology. Effect modification by ZCTA-level (neighbourhood) SES was examined via stratification. RESULTS: We observed stronger air pollution-paediatric asthma associations in 'deprivation areas' (eg, ≥20% of the ZCTA population living in poverty) compared with 'non-deprivation areas'. When stratifying analyses by quartiles of neighbourhood SES, ORs indicated stronger associations in the highest and lowest SES quartiles and weaker associations among the middle quartiles. CONCLUSIONS: Our results suggest that neighbourhood-level SES is a factor contributing vulnerability to air pollution-related paediatric asthma morbidity in Atlanta. Children living in low SES environments appear to be especially vulnerable given positive ORs and high underlying asthma ED rates. Inconsistent findings of effect modification among previous studies may be partially explained by choice of SES stratification criteria, and the use of multiplicative models combined with differing baseline risk across SES populations.