Asthma: where is it going?
Asthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Although our understanding of its pathophysiological mechanisms continues to evolve, the relative contributions of airway hyperresponsiveness and inflammation are still debated. The first mechanism identified as important for asthma was bronchial hyperresponsiveness. In a second step, asthma was recognized also as an inflammatory disease, with chronic inflammation inducing structural changes or remodeling. However, persistence of airway dysfunction despite inflammatory control is observed in chronic severe asthma of both adults and children. More recently, a potential role for epithelial-mesenchymal communication or transition is emerging, with epithelial injury often resulting in a self-sustaining phenotype of wound repair modulation by activation/reactivation of the epithelial-mesenchymal trophic unit, suggesting that chronic asthma can be more than an inflammatory disease. It is noteworthy that the gene-environmental interactions critical for the development of a full asthma phenotype involve processes similar to those occurring in branching morphogenesis. In addition, a central role for airway smooth muscle in the pathogenesis of the disease has been explored, highlighting its secretory function as well as different intrinsic properties compared to normal subjects. These new concepts can potentially shed light on the mechanisms underlying some asthma phenotypes and improve our understanding of the disease in terms of the therapeutic strategies to be applied. How we understand asthma and its mechanisms along time will be the focus of this overview.
Faffe
D S
DS
Laboratório de Fisiologia da Respiração, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, 21941-902 Rio de Janeiro, RJ, Brasil. faffe@biof.ufrj.br
D001249:Asthma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008648:Mesoderm / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D010641:Phenotype