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Background:Household air pollution due to biomass combustion for residential heating adversely affects vulnerable populations. Randomized controlled trials to improve indoor air quality in homes of children with asthma are limited, and no such studies have been conducted in homes using wood for heating.Objectives:Our aims were to test the hypothesis that household-level interventions, specifically improved-technology wood-burning appliances or air-filtration devices, would improve health measures, in particular Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores, relative to placebo, among children living with asthma in homes with wood-burning stoves.Methods:A three-arm placebo-controlled randomized trial was conducted in homes with wood-burning stoves among children with asthma. Multiple preintervention and postintervention data included PAQLQ (primary outcome), peak expiratory flow (PEF) monitoring, diurnal peak flow variability (dPFV, an indicator of airway hyperreactivity) and indoor particulate matter (PM) PM2.5.Results:Relative to placebo, neither the air filter nor the woodstove intervention showed improvement in quality-of-life measures. Among the secondary outcomes, dPFV showed a 4.1 percentage point decrease in variability [95% confidence interval (CI)=−7.8 to −0.4] for air-filtration use in comparison with placebo. The air-filter intervention showed a 67% (95% CI: 50% to 77%) reduction in indoor PM2.5, but no change was observed with the improved-technology woodstove intervention.Conclusions:Among children with asthma and chronic exposure to woodsmoke, an air-filter intervention that improved indoor air quality did not affect quality-of-life measures. Intent-to-treat analysis did show an improvement in the secondary measure of dPFV.Trial registration:ClincialTrials.gov NCT00807183. https://doi.org/10.1289/EHP849

Endocrine disrupting chemicals (EDCs) pose a public health risk through disruption of normal biological processes. Identifying toxicoepigenetic mechanisms of developmental exposure-induced effects for EDCs, such as phthalates or bisphenol A (BPA), is essential. Here, we investigate whether maternal exposure to EDCs is predictive of infant DNA methylation at candidate gene regions. In the Michigan Mother-Infant Pairs (MMIP) cohort, DNA was extracted from cord blood leukocytes for methylation analysis by pyrosequencing (n = 116) and methylation changes related to first trimester levels of 9 phthalate metabolites and BPA. Growth and metabolism-related genes selected for methylation analysis included imprinted (IGF2, H19) and non-imprinted (PPARA, ESR1) genes along with LINE-1 repetitive elements. Findings revealed decreases in methylation of LINE-1, IGF2, and PPARA with increasing phthalate concentrations. For example, a log unit increase in ΣDEHP corresponded to a 1.03 [95% confidence interval (CI): -1.83, -0.22] percentage point decrease in PPARA methylation. Changes in DNA methylation were also inversely correlated with PPARA gene expression determined by RT-qPCR (r = -0.34, P = 0.02), thereby providing evidence in support of functional relevance. A sex-stratified analysis of EDCs and DNA methylation showed that some relationships were female-specific. For example, urinary BPA exposure was associated with a 1.35 (95%CI: -2.69, -0.01) percentage point decrease in IGF2 methylation and a 1.22 (95%CI: -2.27, -0.16) percentage point decrease in PPARA methylation in females only. These findings add to a body of evidence suggesting epigenetically labile regions may provide a conduit linking early exposures with disease risk later in life and that toxicoepigenetic susceptibility may be sex specific.

Epigenetic drift and age-related methylation have both been used in the literature to describe changes in DNA methylation that occurs with aging. However, ambiguity remains regarding the exact definition of both of these terms, and neither of these fields of study explicitly considers the impact of environmental factors on the aging epigenome. Recent twin studies have demonstrated longitudinal, pair-specific discordance in DNA methylation patterns, suggesting an effect of the environment on age-related methylation and/or epigenetic drift. Supporting this idea, other new reports have shown clear environment- and toxicant-mediated shifts away from the baseline rates of age-related methylation and epigenetic drift within an organism, a process we now term "environmental deflection." By defining and delineating environmental deflection, this contemporary review aims to highlight the effects of specific toxicological factors on the rate of DNA methylation changes that occur over the life course. In an effort to inform future epigenetics-based toxicology studies, a field of research now classified as toxicoepigenetics, we provide clear definitions and examples of "epigenetic drift" and "age-related methylation," summarize the recent evidence for environmental deflection of the aging epigenome, and discuss the potential functional effects of environmental deflection.

Epidemiological and animal data suggest that adult chronic disease is influenced by early-life exposure-induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic- and activity-related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of 4 representative IAPs in adult mice exposed to human physiologically-relevant levels of Pb two weeks prior to mating through lactation. When IAPs across the genome were evaluated globally, average (sd) methylation levels were 92.84% (3.74) differing by tissue (p<0.001), but not sex or dose. By contrast, the 4 individual IAPs displayed tissue-specific Pb and sex effects. Medium Pb-exposed mice had 3.86% less brain methylation at IAP 110 (p<0.01), while high Pb-exposed mice had 2.83% less brain methylation at IAP 236 (p=0.01) and 1.77% less at IAP 506 (p=0.05). Individual IAP DNA methylation differed by sex for IAP 110 in the brain and kidney, IAP 236 in the kidney, and IAP 1259 in the kidney. Using Tomtom, we identified 3 binding motifs that matched to each of our novel IAPs impacted by Pb, one of which (HMGA2) has been linked to metabolic-related conditions in both mice and humans. Thus, these recently identified IAPs display tissue-specific environmental lability as well as sex-specific differences supporting an epigenetic link between early exposure to Pb and later-in-life health outcomes.