Immunological Aspects of Allergic Asthma

Asthma is a chronic obstructive disease of the lower airways. It is characterized by episodic exacerbations of at least partially reversible airflow limitation, along with bronchial hyperreactivity and airway inflammation. This latter characteristic, airway inflammation, is now a major focus of investigation, in large part because of a growing body of evidence to support its critical role in the pathogenesis of this disorder. Investigations of the histopathologic, cytologic, and chemical events accompanying fatal and nonfatal asthma, as well as experimental allergen-induced allergic reactions of the lower airways, have confirmed that a wide variety of immunologic phenomena occur, including local release of preformed mediators, newly synthesized metabolites of arachidonic acid, and soluble pro-inflammatory proteins including kinins and cytokines; alterations in vascular permeability and the development of airways edema; leukocyte activation and accumulation; and immune-mediated neurogenic responses that affect airway smooth muscle and other local responses. This information has led to new pharmacologic approaches designed to antagonize each of these elements of the asthmatic diathesis, with varying degrees of success. Nevertheless, the development of novel antagonists of mediators, pro-inflammatory proteins, cells, adhesion molecules, neuropeptides, and their respective receptors have begun to yield additional insight into their relative importance in the immunologic basis of asthma.