From the National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver.
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).
Wenzel SE. Antileukotriene Drugs in the Management of Asthma. JAMA. 1998;280(24):2068–2069. doi:10.1001/jama.280.24.2068
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