New perspectives for asthma treatment: anti-leukotriene drugs

Leukotrienes are synthesized by different cells, including eosinophils, neutrophils, basophils, lymphocytes, macrophages, and mast cells. Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are the most important leukotrienes in the pathogenesis of asthma. Pharmacologically, there are two different ways of blocking the action of leukotrienes: inhibiting their production by blocking 5-lipoxygenase or its activating protein, 5-lipoxygenase-activating protein (FLAP), (inhibitors) or by blocking their receptors (antagonists). The available antagonists are, for the moment, directed against the one receptor demonstrated to play a role in asthma symptoms, CysLT1, and they act in a competitive way. The only marketed 5-lipoxygenase inhibitor is zileuton (Zyflo). CysLT1 antagonists, currently on the pharmaceutical market in some countries, are zafirlukast (Accolate), pranlukast (Ultair, Onon), and montelukast (Singulair). Undoubtedly, drugs acting on leukotrienes constitute a new pharmacologic class in the therapeutic armamentarium for the management of asthma. From the pediatric point of view, montelukast is currently the most interesting drug of the group to date because of published trials in patients as young as 6 yr of age. At present, zafirlukast is only approved for use in patients 12 yr of age and older, although we understand that applications are likely to extend the age range into childhood shortly. However, more experience is necessary to establish a definite place for both leukotrienes in the step-by-step asthma treatment. New comparative studies (with sodium cromoglycate and inhaled steroids), which will probably be published in the near future, as well as studies on the use of montelukast in the treatment of children under 6 yr of age will add crucial information to our knowledge, and help to identify an appropriate use in the therapeutic algorithm. Montelukast will not be a substitute for inhaled corticosteroids or beta-agonists, although it may act as a 'sparing drug' (which might help tapering of steroids in some instances). Its role in exercise-induced asthma seems promising. Although its more widespread use could highlight low-frequency adverse effects, its apparent excellent tolerability is an additional advantage for the drug. Patients' preference for a twice-daily dosage over the inhaled medication, resulting in a better compliance, is relatively well established, at least for zafirlukast in adults, and these findings can probably be extended to montelukast, which only requires once-daily dosing in children.