Asthma: where is it going?

Abstract

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.

Polymerized Type I Collagen Reverts Airway Hyperresponsiveness and Fibrosis in a Guinea Pig Asthma Model

“…In the current study we have found that PtI-collagen displays anti-inflammatory, antifibrotic and functional properties in a guinea pig asthma model. Asthma is an airway inflammatory chronic disease that exhibits heterogeneous and variable symptoms derived from airway physiologic abnormalities (Busse & Lemanske, 2001;Faffe, 2008;Hargreave, In press;Jenkins et al, 2005;Lemanske & Busse, 2010). A typical inflammatory response in asthma exacerbation is a transient influx of neutrophils, followed by eosinophils accumulation (Fahy, 2009;Taube et al, 2003;Venge, 2010).…”

Epithelial-Mesenchymal Transition in Atopy: A Mini-Review

“…While heterogeneous in its pathology, asthma is characterized by intermittent cough, wheezing, and shortness of breath due to lower airway inflammation and/or spasms (42). Increased EMT in bronchial epithelial cells has been hypothesized to contribute to asthma barrier dysfunction (44). Hallmarks of asthma include airway hyperresponsiveness (to triggers such as allergens or exercise) as well as airway remodeling.…”

Doenças respiratórias e fatores associados: Inquérito de Saúde no Município de São Paulo ISA-CAPITAL 2008

“…Na asma, a hiperresponsividade brônquica pode ser desencadeada por alérgenos e por estímulos específicos, como por exemplo, substâncias irritantes, poluição atmosférica, infecções respiratórias, refluxo gastroesofágico, estimulantes farmacológicos, fatores emocionais e exercício físico (BLEASE et al, 2000;FAFFE, 2008). Os mecanismos relacionados com a hiperresponsividade brônquica são múltiplos: inflamação aguda e crônica, remodelamento das vias aéreas (especialmente a hipertrofia da musculatura lisa brônquica), alterações da mecânica das vias aéreas, perda dos fatores que se opõem ao encurtamento do músculo liso e perda da retração elástica do parênquima pulmonar.…”