The role of leukotriene inhibitors in patients with paranasal sinus disease.

Leukotrienes are inflammatory mediators that are known as the slow-reacting substance of anaphylaxis produced by a number of cell types including mast cells, eosinophils, basophils, macrophages, and monocytes. Synthesis of these mediators results from the cleavage of arachidonic acid in cell membranes, and they exert their biologic effects by binding and activating specific adaptors. This occurs in a series of events that lead to contraction of the human airway smooth muscle, chemotaxis, and increased vascular permeability. These effects have led to their important role in the diseases of asthma, allergic rhinitis, and possible paranasal sinusitis with the formation of nasal polyps. Because these agents lead to the production of symptoms in patients that are asthmatic, the use of leukotriene enzyme inhibitors, particularly montelukast, and zafirlukasts seem appropriate. These classes of drugs can block the binding of leukotrienes to CysLT(1) receptors. Zileuton is a 5-lipoxygenase inhibitor that prevents the formation of leukotrienes and can also result in the prevention of leukotriene activity. Demonstrated efficacy in these patients in a number of studies has also suggested their role in inhibiting nasal symptoms in asthmatic patients. In addition, it has been suggested by serendipitous observations that many of the aspirin-intolerant patients have nasal polyps and that treatment with the leukotriene inhibitors has resulted in improvement and resolution of the polyps. Therefore, these agents may also play a role in patients afflicted with chronic sinusitis with concomitant nasal polyposis. These papers are discussed in detail because this form of therapy may represent a novel way to treat patients with this malady in addition to or in lieu of surgical treatment and steroid therapy.