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Contempo 1998
December 23/30, 1998

Antileukotriene Drugs in the Management of Asthma

Author Affiliations

From the National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver.

JAMA. 1998;280(24):2068-2069. doi:10.1001/jama.280.24.2068

DESPITE ADVANCES in the understanding and treatment of the inflammatory processes that mediate the clinical symptoms of asthma,1 the mortality and morbidity associated with this disease have not appreciably declined.2 It continues to be imperative to develop new approaches to asthma therapy. Antileukotriene drugs are a novel form of asthma pharmacotherapy and the first new treatment strategy for chronic asthma in 20 years. In experimental studies, cysteinyl leukotrienes (LTC4, LTD4, and LTE4, together known formerly as slow-reacting substance of anaphylaxis or SRS-A) were found to be extremely potent bronchoconstrictors and to attract inflammatory cells, increase mucous production, and alter vascular permeability.3 LTB4 was found to be a potent chemoattractant for neutrophils and eosinophils, but not to have a bronchoconstrictive effect.3 The cysteinyl leukotrienes were also shown to be produced by activated inflammatory cells (eosinophils, basophils, and mast cells) known to be present in the airways of patients with asthma,3 and were recovered in increased amounts at baseline, after allergen challenge, and during asthma exacerbations from bronchoalveolar lavage fluid and urine of patients with asthma.3-5 These observations suggested that leukotrienes could be important in the clinical symptoms and physiologic changes of asthma, but confirmation of that concept required the development of drugs that either blocked the synthesis of leukotrienes from arachidonic acid (5-lipoxygenase [5-LO] inhibitors and 5-lipoxygenase activating protein [FLAP] inhibitors) or antagonized the activity of the cysteinyl leukotrienes at their receptor, cysLT1 (leukotriene receptor antagonists).