The structural and functional consequences of chronic allergic inflammation of the airways

Abstract

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.