Recent studies suggest that epigenetic regulation (heritable changes in gene expression that occur in the absence of alterations in DNA sequences) may in part mediate the complex gene-by-environment interactions that can lead to asthma. The variable natural history of asthma (i.e., incidence and remission of symptoms) may be a result of epigenetic changes, such as DNA methylation, covalent histone modifications, microRNA changes, and chromatin alterations, after early or later environmental exposures. Findings from multiple epidemiologic and experimental studies indicate that asthma risk may be modified by epigenetic regulation. One study suggested that the transmission of asthma risk may occur across multiple generations. Experimental studies provide substantial in vitro data indicating that DNA methylation of genes critical to T-helper cell differentiation may induce polarization toward or away from an allergic phenotype. Despite this initial progress, fundamental questions remain that need to be addressed by well-designed research studies. Data generated from controlled experiments using in vivo models and/or clinical specimens collected after environmental exposure monitoring are limited. Importantly, cohort-driven epigenetic research has the potential to address key questions, such as those concerning the influence of timing of exposure, dose of exposure, diet, and ethnicity on susceptibility to asthma development. There is immense promise that the study of environmental epigenetics will help us understand a theoretically preventable environmental disease.

Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon (IFN)-γ promoters are associated with T helper (Th) 2 polarization in vitro. No previous studies have examined whether air pollution or allergen exposure alters methylation of these two genes in vivo. We hypothesized that diesel exhaust particles (DEP) would induce hypermethylation of the IFN-γ promoter and hypomethylation of IL-4 in CD4⁺ T cells among mice sensitized to the fungus allergen Aspergillus fumigatus. We also hypothesized that DEP-induced methylation changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Purified DNA from splenic CD4⁺ cells underwent bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were compared with methylation levels at several CpG sites in the IL-4 and IFN-γ promoter. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG⁻⁴⁵, CpG⁻⁵³, CpG⁻²⁰⁵ sites of the IFN-γ promoter and hypomethylation at CpG⁻⁴⁰⁸ of the IL-4 promoter. Altered methylation of promoters of both genes was correlated significantly with changes in IgE levels. This study is the first to demonstrate that inhaled environmental exposures influence methylation of Th genes in vivo, supporting a new paradigm in asthma pathogenesis.

The application of benzo(a)pyrene (BaP)-toxic equivalent factor to polycyclic aromatic hydrocarbons (PAH) concentrations can provide a more accurate risk assessment from environmental exposure to PAH. We hypothesized that BaP-equivalent toxicity determined following residential air monitoring among young urban children may vary by season. Residential indoor and outdoor air levels of PAH measured over two-weeks in a cohort of 5–6 year old children (n = 260) in New York City were normalized to the cancer and mutagen potency equivalent factor of BaP (BaP = 1). Data are presented as carcinogenic equivalents (BaP-TEQ) and mutagenic equivalents (BaP-MEQ) for the sum of 8 PAH (∑₈PAH; MW ³ 228) and individual PAH and compared across heating versus nonheating seasons. Results show that heating compared to nonheating season was associated significantly with higher (BaP-TEQ)_∑8PAH and (BaP-MEQ)_∑8PAH both indoors and outdoors (p < 0.001). Outdoor (BaP-TEQ)_∑8PAH and (BaP-MEQ)_∑8PAH were significantly higher than the corresponding indoor measures during the heating season (p < 0.01). These findings suggest that at levels encountered in New York City air, especially during the heating season, residential exposure to PAH may pose an increased risk of cancer and mutation.

Rationale: The effects of exposure to specific components of ambient fine particulate matter (PM2.5), including metals and elemental carbon (EC), have not been fully characterized in young children. Objectives: To compare temporal associations among PM2.5; individual metal constituents of ambient PM2.5, including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal reports of respiratory symptoms through 24 months of age. Methods: Study participants were selected from the Columbia Center for Children's Environmental Health birth cohort recruited in New York City between 1998 and 2006. Respiratory symptom data were collected by questionnaire every 3 months through 24 months of age. Ambient pollutant data were obtained from state-operated stationary monitoring sites located within the study area. For each subject, 3-month average inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM2.5 were calculated for each symptom-reporting period based on the questionnaire date and the preceding 3 months. Associations between pollutants and symptoms were characterized using generalized additive mixed effects models, adjusting for sex, ethnicity, environmental tobacco smoke exposure, and calendar time. Measurements and Main Results: Increases in ambient Ni and V concentrations were associated significantly with increased probability of wheeze. Increases in EC were associated significantly with cough during the cold/flu season. Total PM2.5 was not associated with wheeze or cough. Conclusions: These results suggest that exposure to ambient metals and EC from heating oil and/or traffic at levels characteristic of urban environments may be associated with respiratory symptoms among very young children.