Epigenetic changes in childhood asthma

Abstract

Two novel conceptual frameworks have captured the imagination of biomedical scientists who are interested in the pathogenesis of chronic and complex diseases. One is epigenetics, which may explain how environmental factors can cause stable alterations in phenotype without changes in genotype. The other is transcriptional regulation by microRNA. In this Commentary, we examine the relevance of epigenetics and the role of microRNA in the induction and progression of asthma in childhood, and propose a model to link these mechanisms. Childhood asthmaAsthma is one of the most common chronic diseases affecting children, especially in economically developed nations. For example, in Australia the prevalence of asthma is 9-11% in the 2-4-year-old age group and 12-16% in the 5-17-year-old age group, with males affected more commonly than females (Ampon et al., 2007). Childhood asthma is linked strongly to atopy, which is a genetic predisposition to produce immunoglobulin E (IgE) antibodies in response to ordinary exposures to environmental allergens, and is often associated with symptoms of asthma, rhinoconjunctivitis or eczema (Johansson et al., 2004). In turn, atopy is associated characteristically with a T helper 2 (Th2)-biased immunological response (Bacharier et al., 2008). However, the pathogenesis of this illness remains incompletely understood. Both genetic predisposition and various environmental factors clearly play important roles in the development of allergic asthma (Sly et al., 2008), but the relative importance of these various contributory mechanisms and the ways in which they might interact are difficult to assess.Epidemiological studies strongly suggest that the most important environmental factors that predispose to the development of asthma are lower respiratory tract viral infections associated with wheezing, especially in early childhood, and repeated inhalation exposure to allergens, which appear to be synergistic (Holt and Sly, 2007;Sly et al., 2008). The role of early-life viral infections is somewhat controversial because the so-called 'hygiene hypothesis' proposed that infections in early childhood, which are acquired by contact with older siblings or other children, might protect against subsequent development of asthma and other allergic diseases (reviewed by Wong and Chow, 2008). However, a recent longitudinal study involving prospective follow-up to 8 years of age strongly suggests that this is unlikely to be a valid notion (Caudri et al., 2009). Among the early-life viral infections, respiratory syncytial virus (RSV) and rhinovirus are of particular interest, because wheezing lower respiratory tract infections in the first year of life are associated strongly with subsequent development of asthma (Kristjansson et al., 2005;Sigurs et al., 2005; Kusel et al., 2007;Jackson et al., 2008; Mohapatra and Boyapalle, 2008). Other clearly defined risk factors are exposure to airborne environmental irritants such as tobacco smoke and traffic pollutants: evidence for their role comes from numerous larg...

Alterations in DNA methylation and airway hyperreactivity in response toin uteroexposure to environmental tobacco smoke

“…It has been clear that epigenetic mechanisms, including DNA methylation may be involved in maintaining Th1 and Th2 lineages (Jones & Chen, 2006; White et al, 2002). In recent years, epigenetic changes have been recognized as a potential mechanism underlying the establishment and maintenance of the Th2 bias in asthmatic and allergic symptoms (Kumar et al, 2009; van Panhuys et al, 2008). In response to allergens, demethylation of Th2 cytokine genes induces a change in the chromatin structure, allowing the DNA to open and recruit transcription factors such as GATA3 for immediate expression of Th2 cytokines (van Panhuys et al, 2008).…”

Transcriptional characteristics of CD4+ T cells in young asthmatic children: RORC and FOXP3 axis

“…Asthma is a chronic inflammatory disorder of the airway 1. Its symptoms are highly variable, and the causes of asthma and their interactions remain largely uncertain 2.…”

IgE anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma

“…But, it should be mentioned, due to our cross-sectional study design, we were unable to determine whether the above differences in subjects with asthma were due to recurrent or prolonged infections. A possible explanation might be that RSV infection might stimulate induction of genes associated with recurrent wheezing [24] or it could be that individuals with abnormal lung function are more susceptible to RSV infection.…”