BASIC MECHANISMS OF ASTHMA

Results of studies of the epidemiology, physiology, histopathology, an d cell biology of asthma have revised our conception of the disease. E pidemiologic studies have shown asthma to be an important cause of dea th, suffering, and economic hardship. Physiologic studies have shown t hat asthma is a chronic illness characterized by persistent bronchial hyperreactivity. Histopathologic studies have shown characteristic cha nges: epithelial damage, deposition of collagen beneath the basement m embrane. eosinophilic and lymphocytic infiltration, and hypertrophy an d hyperplasia of goblet cells, submucosal glands. and airway smooth mu scle. Studies of the functions of cells in the airway mucosa suggest t hat asthma may be fundamentally mediated by a difference in the type o f lymphocyte predominating in the airway mucosa but may also involve c omplex interactions among resident and migratory cells. Asthma may thu s result from sensitization of a subpopulation of CD4+ lymphocytes, th e Th2 subtype. in the airways. These lymphocytes produce a family of c ytokines that favor IgE production and the growth and activation of ma st cells and eosinophils. arming the airways with the mechanisms of re sponse to subsequent reexposure to the allergen. This conceptual model has stimulated research along lines that will almost certainly lead t o powerful new treatments. and it has already put current therapies in a new light, clarifying the role of antiinflammatory agents, especial ly of inhaled corticosteroids. This conceptual model has some limitati ons: it ignores new evidence on the role of the mast cell in producing cytokines and depends on results of studies of the effects of inhalat ion of allergen, although most asthma exacerbations are provoked by vi ral respiratory infection. Preliminary studies suggest that viral infe ction and allergen inhalation may involve the activation of different pathways, with viral infection activating production of cytokines by a irway epithelia cells. Similar study of the mechanisms activated by in halation of air toxics may provide important clues as to how they migh t induce or exacerbate asthma.