Air pollution exposure and novel biomarkers of inflammation and cardiac stress in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Thesis (Master's)--University of Washington, 2016-06Epidemiologic evidence indicates a causal association between long-term air pollution exposure and cardiovascular disease (CVD), but the mechanisms underlying this process are not fully understood. Inflammation in the lungs that spreads to the rest of the body may result in systemic oxidative stress and inflammation. Subsequently, this inflammatory state may lead to endothelial dysfunction, atherosclerosis, increased coagulation, and activation of the renin-angiotensin system. Some studies have utilized measures of subclinical disease or biomarkers to support these potential mechanisms for the effect of air pollution on the development of CVD. This analysis investigated the effects of long-term exposure to air pollution, specifically four pollutants: fine particulate matter (PM2.5), oxides of nitrogen (NOx), nitrogen dioxide (NO2), and black carbon (BC). This paper examined the association between long-term exposure and the following novel biomarkers of cardiac stress and inflammation: (1) N-terminal-pro-B-type natriuretic peptide (NT-proBNP), (2) Pentraxin-3 (PTX3), and (3) Serum Amyloid P (SAP). As a secondary aim, this paper examined the association between short-term exposures to PM2.5 and each of the biomarkers of interest. Data from a prospective cohort study, the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) in six US cities, were used for this analysis. Likelihood-based spatiotemporal models were used to calculate air pollution exposures at participant residences. NT-proBNP was measured at baseline (n=5,597) and again at a follow-up exam (n=4,694), which was on average three years after baseline. PTX3 and SAP were both measured at the baseline exam in a subset of participants (n=2,878) selected in equal proportions from each racial/ethnic group. NT-proBNP and PTX3 were log-transformed for analysis; SAP was modeled on the natural scale. No association was found between air pollution and NT-proBNP in a repeated measures analysis, but an association was observed between air pollution and elevated levels (≥125 pg/mL) of NT-proBNP at Exam 3 among those with a normal NT-proBNP level at baseline (i.e. reflecting incident cases of sub-clinical cardiac stress and/or sub-clinical heart failure). For a 15 ppb increase in NO2 exposure, the odds ratio was 1.88 (95% CI: 1.20, 2.95; p=0.006) and for a 0.7 10-5 m-1 increase in BC exposure the odds ratio was 1.72 (95% CI: 1.07, 2.76; p=0.026). Increased exposure to PM2.5 was associated with a 2.5 µg/mL increase in SAP (95% CI: 0.3, 4.8; p=0.025), though no associations were found with NOx, NO2, or BC. In cross-sectional analyses, no association was observed between air pollution and PTX3. No associations were found between short-term exposure to PM2.5 and NT-proBNP, PTX3, or SAP

Residential green space and behavioral and mental health in early childhood

Thesis (Ph.D.)--University of Washington, 2021University of WashingtonAbstract Residential green space and behavioral and mental health in early childhood Marnie F. Hazlehurst Chair of the Supervisory Committee:Catherine Karr Departments of Environmental and Occupational Health Sciences, Pediatrics, and Epidemiology Background Natural environments, including urban green spaces, have been associated with a range of health outcomes across the life course. Green space may promote healthy development, even early in childhood. The aim of this study was to investigate the relationships between residential green space exposures and child behavioral and mental health in a socio-demographically diverse cohort in Memphis, TN. We also explored the relationship of green space measures to a broad set of neighborhood conditions, including socioeconomic and education resources. Methods We assessed three green space exposures—residential surrounding greenness, tree cover, and park proximity—within the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort. Behavioral and mental health outcomes at age 4, including both externalizing and internalizing behaviors, were assessed via parent-report on the Child Behavior Checklist (CBCL). Linear regression models adjusted for individual, household, and neighborhood-level confounders across multiple domains, were fit to assess the relationship between green space and child behavior. Effect modification by neighborhood socioeconomic opportunity and child sex were explored using multiplicative interaction terms. Results Higher residential surrounding greenness was associated with lower internalizing behavior scores. Observed associations were generally robust across a suite of sensitivity analyses, including adjustment for potential mediators. In secondary analyses, these associations were most consistent for the anxious/depressed and somatic complaints syndrome scales. We did not find any associations with externalizing behaviors or attention problems. In this study, residential surrounding greenness and tree cover were higher in neighborhoods with a higher homeownership rate, more early childhood education resources, and a lower percentage of Black residents. Conclusions Findings from this dissertation add to the accumulating evidence of a protective effect of residential green space for mental health in early childhood. Strengths of this study include the spatial resolution of green space measures and the assessment of behavior outcomes across a continuum. Future work may improve our understanding of these relationships by incorporating child care or school-based exposures and assessing time spent in green spaces. This research can inform the design of new green spaces or the conservation and management of existing urban green spaces, including improving access to nature features such as trees within historically underserved communities, as well as interventions targeting families with young children

Individual and Neighborhood Stressors, Air Pollution and Cardiovascular Disease

Psychosocial and environmental stress exposures across the life course have been shown to be relevant in the development of cardiovascular disease (CVD). Assessing more than one stressor from different domains (e.g., individual and neighborhood) and across the life course moves us towards a more integrated picture of how stress affects health and well-being. Furthermore, these individual and neighborhood psychosocial stressors act on biologic pathways, including immune function and inflammatory response, which are also impacted by ubiquitous environmental exposures such as air pollution. The objective of this study is to evaluate the interaction between psychosocial stressors, at both the individual and neighborhood level, and air pollution on CVD. This study used data from the 2009–2011 Behavioral Risk Factor Surveillance System (BRFSS) from Washington State. Adverse childhood experiences (ACEs) measured at the individual level, and neighborhood deprivation index (NDI) measured at the zip code level, were the psychosocial stressors of interest. Exposures to three air pollutants—particulate matter (both PM2.5 and PM10) and nitrogen dioxide (NO2)—were also calculated at the zip code level. Outcome measures included several self-reported CVD-related health conditions. Both multiplicative and additive interaction quantified using the relative excess risk due to interaction (RERI), were evaluated. This study included 32,151 participants in 502 unique zip codes. Multiplicative and positive additive interactions were observed between ACEs and PM10 for diabetes, in models adjusted for NDI. The prevalence of diabetes was 1.58 (95% CI: 1.40, 1.79) times higher among those with both high ACEs and high PM10 compared to those with low ACEs and low PM10 (p-value = 0.04 for interaction on the multiplicative scale). Interaction was also observed between neighborhood-level stressors (NDI) and air pollution (NO2) for the stroke and diabetes outcomes on both multiplicative and additive scales. Modest interaction was observed between NDI and air pollution, supporting prior literature on the importance of neighborhood-level stressors in cardiovascular health and reinforcing the importance of NDI on air pollution health effects. ACEs may exert health effects through selection into disadvantaged neighborhoods and more work is needed to understand the accumulation of risk in multiple domains across the life course

Residential proximity to greenhouse agriculture and neurobehavioral performance in Ecuadorian children

BackgroundChildren living near greenhouse agriculture may have an increased risk of pesticide exposure due to drift or direct contact with pesticide-treated areas. However, little is known about whether this increased potential for chronic exposure may impair their neurodevelopment.MethodsWe examined 307 children aged 4-9 years, living in agricultural communities in Ecuador (ESPINA study). The two exposures calculated were residential distance from the nearest flower plantation perimeter and flower plantation surface area within 100 m of homes. Five neurobehavioral domains were assessed: Attention/Inhibitory Control, Memory/Learning, Visuospatial processing and Sensorimotor (higher values reflect better performance). Low scores were defined according to the test's cut-offs. Models were adjusted for demographic, socio-economic and growth variables.ResultsThe mean (SD) residential distance to the nearest flower plantation was 446 m (344). Living 100 m closer to crops was associated with increased odds (OR [95% CI]) of low scores in the domains of Memory/Learning (1.24 [1.05, 1.46]) and Language (1.09 [1.00, 1.19]). Associations were strongest among children living within 50 m, having significantly lower scores in Language (-1.28 which is ~50% of a SD [-2.50, -0.06]), Attention/Inhibitory Control (-1.24 units, [-2.45, -0.04]), and Memory/Learning (-0.91, [-1.99, 0.17]), compared to children living farther than 500 m. Analyses of areas of flower crops near homes concurred with these findings.ConclusionsClose residential proximity to greenhouse floricultural crops was associated with adverse neurobehavioral performance in Attention/Inhibitory Control, Language and Memory/Learning among children. This highlights the importance of reducing pesticide drift from plantations to nearby homes

Integrating data from multiple time-location measurement methods for use in exposure assessment : the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Tools to assess time-location patterns related to environmental exposures have expanded from reliance on time-location diaries (TLDs) and questionnaires to use of geospatial location devices such as data-logging Global Positioning System (GPS) equipment. The Multi-Ethnic Study of Atherosclerosis and Air Pollution obtained typical time-location patterns via questionnaire for 6424 adults in six US cities. At a later time (mean 4.6 years after questionnaire), a subset (n=128) participated in high-resolution data collection for specific 2-week periods resulting in concurrent GPS and detailed TLD data, which were aggregated to estimate time spent in various microenvironments. During these 2-week periods, participants were observed to spend the most time at home indoors (mean of 78%) and a small proportion of time in-vehicle (mean of 4%). Similar overall patterns were reported by these participants on the prior questionnaire (mean home indoors: 75%; mean in-vehicle: 4%). However, individual micro-environmental time estimates measured over specific 2-week periods were not highly correlated with an individual's questionnaire report of typical behavior (Spearman's ρ of 0.43 for home indoors and 0.39 for in-vehicle). Although questionnaire data about typical time-location patterns can inform interpretation of long-term epidemiological analyses and risk assessment, they may not reliably represent an individual's short-term experience

Individual and Neighborhood Level Predictors of Childrens Exposure to Residential Greenspace.

Inequities in urban greenspace have been identified, though patterns by race and socioeconomic status vary across US settings. We estimated the magnitude of the relationship between a broad mixture of neighborhood-level factors and residential greenspace using weighted quantile sum (WQS) regression, and compared predictive models of greenspace using only neighborhood-level, only individual-level, or multi-level predictors. Greenspace measures included the Normalized Difference Vegetation Index (NDVI), tree canopy, and proximity of the nearest park, for residential locations in Shelby County, Tennessee of children in the CANDLE cohort. Neighborhood measures include socioeconomic and education resources, as well as racial composition and racial residential segregation. In this sample of 1012 mother-child dyads, neighborhood factors were associated with higher NDVI and tree canopy (0.021 unit higher NDVI [95% CI: 0.014, 0.028] per quintile increase in WQS index); homeownership rate, proximity of and enrollment at early childhood education centers, and racial composition, were highly weighted in the WQS index. In models constrained in the opposite direction (0.028 unit lower NDVI [95% CI: - 0.036, - 0.020]), high school graduation rate and teacher experience were highly weighted. In prediction models, adding individual-level predictors to the suite of neighborhood characteristics did not meaningfully improve prediction accuracy for greenspace measures. Our findings highlight disparities in greenspace for families by neighborhood socioeconomic and early education factors, and by race, suggesting several neighborhood indicators for consideration both as potential confounders in studies of greenspace and pediatric health as well as in the development of policies and programs to improve equity in greenspace access

Associations of residential green space with internalizing and externalizing behavior in early childhood.

BACKGROUND: Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4-6 years. METHODS: Childrens internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures-residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity-averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms. RESULTS: Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant. CONCLUSIONS: Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health

Role of Air Pollution in the Development of Asthma Among Children with a History of Bronchiolitis in Infancy.

BACKGROUND: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year. METHODS: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported childrens current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models. RESULTS: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma. CONCLUSION: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis