[Leukotriene antagonists in the treatment of asthma]

Bronchial asthma is a chronic inflammatory disease of the airways. Several mediators are involved in the inflammatory process, including leukotrienes B4, C4, D4 and E4. These compounds promote bronchoconstriction, mucus hypersecretion, eosinophil infiltration, monocyte/macrophage activation, and smooth muscle proliferation. Two different approaches have been taken to interfere with activity: 1) blocking of the specific cysteinyl leukotriene receptor, and 2) inhibition of leukotriene biosynthesis (either by inhibition of the primary enzyme, 5-lipoxygenase, or its required cofactor 5-lipoxygenase-activating-protein). Available data suggest that leukotriene modifier therapy is effective in several experimental models of bronchial asthma. These agents also have demonstrable efficacy in aspirin-induced asthma and against exercise and cold-air-induced bronchoconstriction. The recent 1997 NHLBI Expert Panel Report II Guidelines suggest that leukotriene modifiers may be used as an alternative to low dose inhaled corticosteroids in mild persistent asthma. They may also be useful in more severe asthma, as supplements to inhaled corticosteroids and long-acting bronchodilators. The clinical benefit of leukotriene modifier therapy occurs early in treatment. However, the response rate for leukotriene modifiers approximates 70 to 80% suggesting that there are "responders" as well as "non-responders" for whom leukotrienes, as inflammatory mediators, may be less important. A 2 to 4-week therapeutic trial, with objective monitoring of response, may be a reasonable approach to initiating leukotriene modifier therapy. Additional controlled trials will be required to define more fully the role of these new drugs for long-term control and treatment of asthma.