Antileukotrienes in the Treatment of Asthma
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PURPOSE: To review the activity in clinical models, the efficacy, and the safety of antileukotrienes as a new class of antiasthma treatment. DATA SOURCES: English-language trials identified from the archival literature, including the MEDLINE database, through 1996; bibliographic references; and textbooks. STUDY SELECTION: Reports from placebo-controlled, double-blind, randomized trials were selected. DATA EXTRACTION: Study designs and results were extracted from the clinical trial reports. Statistical evaluation of combined results was not attempted. DATA SYNTHESIS: The various classes of antileukotrienes have shown activity in clinical models of asthma, including exercise-induced, cold air hyperventilation-induced, allergen-induced, and aspirin-induced bronchoconstriction. In addition, the antileukotrienes partially reverse spontaneous bronchoconstriction in asthmatic persons, an effect additive to that of inhaled beta 2-agonists. Clinical trials of the antileukotrienes have shown clinical benefit, as measured by reductions in asthma symptom scores, improvements in air flow obstruction, and reductions in the rescue use of inhaled beta 2-agonists. Some, but not all, of the antileukotrienes have been shown to cause liver microsomal activation with increases in hepatic aminotransferase levels. CONCLUSIONS: Antileukotrienes are an important new therapy for asthma. Inhibition of leukotriene synthesis or action has a beneficial effect in the treatment of both induced and spontaneous asthma. These results show that leukotrienes are important mediators of the asthmatic response. In addition, encouraging results have been obtained from clinical trials of antileukotrienes; however, these results do not yet provide guidelines for the optimal clinical use of antileukotrienes in asthma treatment. Such recommendations await the results of further studies.
