Paré P D, Bai T R, Roberts C R
Respiratory Health Network of Centres of Excellence, University of British Columbia, Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Ciba Found Symp. 1997;206:71-86; discussion 86-9, 106-10. doi: 10.1002/9780470515334.ch5.
Although asthma is generally considered a form of reversible airway obstruction, there is evidence that chronic allergic inflammation can lead to structural changes in the airway and a degree of progressive fixed airway obstruction. More importantly, these structural changes can lead to airway hyper-responsiveness. The structural consequences of chronic allergic inflammation are secondary to cellular proliferation and reorganization of the connective tissue constituents of the airway wall. Smooth muscle proliferation and hypertrophy may increase the potential for smooth muscle shortening against the elastic loads provided by lung parenchymal recoil and airway mucosal folding. Resident airway cells, as well as inflammatory cells, produce mediators, cytokines and growth factors that stimulate production of connective tissue proteins and proteoglycans that cause airway remodelling and altered mechanical function. Thickening of the airway wall internal to the smooth muscle layer can amplify the effect of smooth muscle shortening on airway calibre, and it could also stiffen the airway making it less distensible. Thickening of the airway wall external to the muscle can uncouple the airway from the distending force applied by the lung parenchyma. Early and aggressive anti-inflammatory medication may alter the natural history of asthma by preventing the structural changes that are a consequence of chronic allergic inflammation.
尽管哮喘通常被认为是一种可逆性气道阻塞形式，但有证据表明，慢性过敏性炎症可导致气道结构改变以及一定程度的进行性固定性气道阻塞。更重要的是，这些结构改变可导致气道高反应性。慢性过敏性炎症的结构后果继发于气道壁结缔组织成分的细胞增殖和重组。平滑肌增殖和肥大可能会增加平滑肌在肺实质回缩和气道黏膜折叠所提供的弹性负荷作用下缩短的可能性。驻留气道细胞以及炎症细胞会产生介质、细胞因子和生长因子，这些物质会刺激结缔组织蛋白和蛋白聚糖的产生，从而导致气道重塑和机械功能改变。平滑肌层内部的气道壁增厚会放大平滑肌缩短对气道管径的影响，还可能使气道变硬，使其扩张性降低。肌肉外部的气道壁增厚会使气道与肺实质施加的扩张力脱耦联。早期积极的抗炎药物治疗可能通过预防慢性过敏性炎症导致的结构改变来改变哮喘的自然病程。
