Airway Smooth Muscle Phenotype and Function: Interactions with Current Asthma Therapies
A. J. Halayko, T. Tran, S. Y. Ji, A. Yamasaki and R. Gosens
Pages 525-540 (16)
Asthma incidence has climbed markedly in the past two decades despite an increased use of medications that suppress airway inflammation and repress contraction of smooth muscle that encircles the airways. Asthmatics exhibit episodes of airway inflammation that potentiates reversible airway smooth muscle spasm. A hallmark diagnostic symptom of asthma is airway hyperresponsiveness to inhaled non-allergic stimuli, such as methacholine, that directly induce airway smooth muscle contraction. Inhaled gluccocorticoids are used for first-line prevention of airway inflammation, and are frequently combined with inhaled β2-adrenoceptor agonists that can effectively relax airway smooth muscle and restore airway conductance. Leukotriene receptor antagonists and anti-cholinergics can also be used in many patients to ensure optimal control of symptoms. With increasing disease duration irreversible airway restriction develops from inflammation- driven fibro-proliferative airway remodeling that includes increased deposition of extracellular matrix, the accumulation of airway smooth muscle, and increased numbers of myofibroblasts. Mature airway smooth muscle cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory functional responses that contribute to airway remodeling and persistent hyperresponsiveness. This review assesses current understanding of acute and chronic effects of common anti-asthma medications on the diverse phenotype and functional characteristics of airway smooth muscle cells. Furthermore, we describe the significance of these effects in the treatment of asthma symptoms and pathogenesis.
airway remodeling, airway hyperresponsiveness, contraction, gene transcription, gluccocorticoids, β2-agonist, leukotriene receptor antagonist, anti-cholinergics
Section of Respiratory Diseases,University of Manitoba, Rm. RS321, Respiratory Hospital, 810 SherbrookStreet, Winnipeg, MB, Canada R3A 1R8.