Airway epithelial–mesenchymal interactions in the pathogenesis of asthma

Abstract

While asthma is an inflammatory disorder of the conducting airways with strong allergic overtones, the variable and often low clinical response to selective treatments that target the Th2 pathway have been disappointing. Beyond mild disease, asthma is a disorder of epithelial damage and aberrant repair with recapitulation of regenerative pathways that are prominent in foetal lung morphogenesis. This has led to the concept of activation of chronic asthma being maintained by persistent activation of the epithelial mesenchymal trophic unit by biologically active allergens, microorganisms and pollutants to drive inflammation in parallel with airway remodelling. Such mechanisms provide a basis for novel therapies directed towards increasing the lung's resistance to the inhaled environment and improving repair rather than concentrating on suppressing inflammation.