Pathophysiology of asthma

Summary The increased knowledge of mucosal cellular events and their regulation within the airways in asthma has been made possible both by the feasibility of direct airway sampling in this disorder by endobronchial biopsy and lavage, and on account of the major advances that have been made in the understanding of the immunological mechanisms involved in inflammation. The appreciation that cell damage and remodelling can arise as a consequence of this inflammation has provided a mechanism whereby the structural abnormalities in asthma may arise. Eosinophil products, such as MBP and ECP, have been shown to be cytotoxic and their release within the epithelium could contribute to damage to this cell population. In addition, collagenases from activated eosinophils, will damage the basement membrane and mast cell derived proteases may loosen intercellular adhesion, both factors which could contribute to epithelial fragility. This epithelial disruption is likely to contribute to bronchial hyperresponsiveness as several reports exist relating epithelial damage to the level of bronchial responsiveness in asthma (53–55) and the epithelium, in addition to generating cytokines, can synthesize bronchodilator substances such as PGE2 and NO, has the capacity to metabolize the bronchoconstrictor SP, through generation of neutral endopeptidases, and contains afferent sensory neurones whose stimulation may be increased in the presence of a disrupted epithelial layer. The deposition of collagen (types III and IV) associated with an increase in tissue myofibroblasts, may reflect an attempt at a repair process (56, 57). This will lead to an increase in airway bulk as will smooth muscle hyperplasia and hypertrophy, both factors which through geometric considerations are likely to contribute to bronchial hyperresponsiveness. Growth factors associated with mast cell, eosinophil and macrophage activation can all be theoretically linked with fibroblast proliferation and activation and smooth muscle mutagenesis. The reduction in mucosal inflammation with corticosteroid therapy in association with improvements in spirometry and bronchial responsiveness (58) provides further support for the inflammatory pathogenesis of the asthma disease.