New perspectives for asthma treatment: Anti-leukotriene drugs

Leukotrienes are synthesized by different cells, including eosinophils, neu trophils, basophils, lymphocytes, macrophages, and mast cells. Cysteinyl le ukotrienes (LTC4, LTD4, and LTE4) are the most important leukotrienes in th e pathogenesis of asthma. Pharmacologically, there are two different ways o f blocking the action of leukotrienes: inhibiting their production by block ing 5-lipoxygenase or its activating protein, 5-lipoxygenase-activating pro tein (FLAP), (inhibitors) or by blocking their receptors (antagonists). The available antagonists are, for the moment, directed against the one recept or demonstrated to play a role in asthma symptoms, CysLT(1), and they act i n a competitive way. The only marketed 5-lipoxygenase inhibitor is zileuton (Zyflo (TM)). CysLT1 antagonists, currently on the pharmaceutical market i n some countries, are zafirlukast (Accolate (TM)), pranlukast (Ultair (TM), Onon (TM)), and montelukast (Singulair (TM)). Undoubtedly, drugs acting on leukotrienes constitute a new pharmacologic class in the therapeutic armam entarium for the management of asthma. From the pediatric point of view, mo ntelukast is currently the most interesting drug of the group to date becau se of published trials in patients as young as 6 yr of age. At present, zaf irlukast is only approved for use in patients 12 yr of age and older, altho ugh we understand that applications are likely to extend the age range into childhood shortly. However, more experience is necessary to establish a de finite place for both leukotrienes in the step-by-step asthma treatment. Ne w comparative studies (with sodium cromoglycate and inhaled steroids), whic h 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 u se in the therapeutic algorithm. Montelukast will not be a substitute for i nhaled corticosteroids or beta-agonists, although it may act as a 'sparing drug' (which might help tapering of steroids in some instances). Its role i n exercise-induced asthma seems promising. Although its more widespread use could highlight low-frequency adverse effects, its apparent excellent tole rability is an additional advantage for the drug. Patients' preference for a twice-daily dosage over the inhaled medication, resulting in a better com pliance, is relatively well established, at least for zafirlukast in adults , and these findings can probably be extended to montelukast, which only re quires once-daily dosing in children.