Department of Allergy and Immunology, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
Curr Mol Pharmacol. 2009 Jun;2(2):169-81. doi: 10.2174/1874467210902020169.
Airway inflammation, airway remodeling and airway hyperresponsiveness are the fundamental components of pathogenesis that lead to symptoms and lung function changes in asthma. Airway remodeling describes the structural changes to the airways in asthma. The remodeling process involves diverse pathological changes including epithelial metaplasia, subepithelial fibrosis, angiogenesis and smooth muscle thickening. Airway remodeling contributes to irreversible loss of lung function and airway hyperresponsiveness. Remodeling is associated with severe and persistent disease but can also occur early in the course of disease pathogenesis and does not resolve spontaneously. Current asthma therapies, for example corticosteroids, are successful in treating allergic inflammation, an important factor contributing to remodeling, but do not specifically target the remodeling process, and remodeling changes progress despite optimal control of inflammation. Moreover, airway remodeling is not eradicated or prevented despite widespread use of anti-inflammatory treatments. There is limited evidence for the effectiveness of leukotriene inhibitors, phosphodiesterase inhibitors, mast cell tryptase inhibitors, and peroxisome proliferator-activated receptor gamma agonists in the treatment or prevention of remodeling changes. The search for novel therapies that can specifically reverse or prevent airway remodeling is an active area of research. Treatments that may be useful in preventing airway remodeling include those that directly or indirectly target single or multiple components of the airway remodeling process. Identification of novel asthma genes may also allow disease targeting. A better understanding of airway remodeling in asthma will facilitate the development of new treatments for asthma beyond control of symptoms and inflammation.
气道炎症、气道重塑和气道高反应性是导致哮喘症状和肺功能变化的发病机制的基本组成部分。气道重塑描述了哮喘中气道的结构变化。重塑过程涉及多种病理变化，包括上皮化生、黏膜下纤维化、血管生成和平滑肌增厚。气道重塑导致肺功能不可逆转的丧失和气道高反应性。重塑与严重和持续的疾病有关，但也可能在疾病发病机制的早期发生，并且不会自发解决。目前的哮喘治疗方法，如皮质类固醇，在治疗导致重塑的过敏炎症方面是成功的，但并不能专门针对重塑过程，并且尽管炎症得到最佳控制，重塑变化仍在进展。此外，尽管广泛使用抗炎治疗，气道重塑仍未消除或预防。白三烯抑制剂、磷酸二酯酶抑制剂、肥大细胞胰蛋白酶抑制剂和过氧化物酶体增殖物激活受体 γ 激动剂在治疗或预防重塑变化方面的有效性证据有限。寻找专门逆转或预防气道重塑的新型疗法是一个活跃的研究领域。可能有助于预防气道重塑的治疗方法包括直接或间接针对气道重塑过程单一或多个成分的治疗方法。新型哮喘基因的鉴定也可能允许针对疾病。更好地了解哮喘中的气道重塑将有助于开发超越控制症状和炎症的哮喘新疗法。
