Long-term effects of the Hebei Spirit oil spill on the prevalence and incidence of allergic disorders

Asthma, a chronic inflammatory disorder of the airway, is influenced by interplay between genetic and environmental factors now known to be mediated by epigenetics. Aberrant DNA methylation, altered histone modifications, specific microRNA expression, and other chromatin alterations orchestrate a complex early-life reprogramming of immune T-cell response, dendritic cell function, macrophage activation, and a breach of airway epithelial barrier that dictates asthma risk and severity in later life. Adult-onset asthma is under analogous regulation. The sharp increase in asthma prevalence over the past 2 or 3 decades and the large variations among populations of similar racial/ethnic background but different environmental exposures favors a strong contribution of environmental factors. This review addresses the fundamental question of whether environmental influences on asthma risk, severity, and steroid resistance are partly due to differential epigenetic modulations. Current knowledge on the epigenetic effects of tobacco smoke, microbial allergens, oxidants, airborne particulate matter, diesel exhaust particles, polycyclic aromatic hydrocarbons, dietary methyl donors and other nutritional factors, and dust mites is discussed. Exciting findings have been generated by rapid technological advances and well-designed experimental and population studies. The discovery and validation of epigenetic biomarkers linked to exposure, asthma, or both might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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.