The role of leukotriene modifiers in the treatment of asthma.

Asthma is a complex syndrome characterized by variable obstruction to airflow, bronchial hyperresponsiveness, and inflammation. The initiation and propagation of airway inflammation arises from many factors, including mediators generated by resident airway cells and recruited leukocytes (1). Leukotrienes are biologically active fatty acids derived from the oxidative metabolism of arachidonic acid, an integral component of the cell membrane (2). A role for leukotrienes in the pathogenesis of asthma has been suggested by their biologic activities, which produce effects that mimic those of clinical asthma, and by the effects of either inhibition of leukotriene production (5-lipoxygenase inhibitors) or antagonism of leukotriene binding to cellular receptors (leukotriene D 4 -receptor antagonists). The recent U.S. Food and Drug Administration (FDA) approval of a leukotriene-receptor antagonist, zafirlukast (Accolate), and a leukotriene synthesis inhibitor, zileuton (Zyflo), provides the first mediator-specific therapy for asthma. This review will consider the biochemistry of the leukotrienes, their biologic role in asthma, and the therapeutic potential of drugs that alter the production or action of leukotrienes, as well as provide guidelines for the use of leukotriene modifiers in patients with asthma.