Targeting cysteinyl leukotrienes in patients with rhinitis, sinusitis and paranasal polyps

Leukotrienes have been known in the field of immunology since the 1930s. At that time they were referred to as the slow reacting substance of anaphylaxis. They were not, however, characterized until the 1980s, when they were noted to be formed during the breakdown of arachidonic acid by the enzyme 5-lipoxygenase. The leukotrienes consist of leukotriene (LT) A4, LTB4, LTC4, LTD4 and LTE4, so named because the molecule was originally isolated from leukocytes and therefore its carbon backbone contains three double bonds in series, which constitutes a trion. This structural information provided the key to the oxidative pathway of lipometabolism, known as the 5-lipoxygenase. Leukotrienes are classified as inflammatory mediators, and therefore they are produced by a number of cell types, particularly mast cells, eosinophils, basophils, macrophages and monocytes. With the identification of asthma, allergic rhinitis and paranasal sinusitis associated with inflammatory pathways, the leukotrienes have been implicated in the pathogenesis of these conditions and have become targets for therapeutic modulation. Leukotriene synthesis inhibitors have been used successfully in the treatment of patients with asthma where they have demonstrated the ability to induce bronchial dilatation, provide protection against broncho-provocation tests and significantly diminish symptoms. When it was serendipitously noted that patients who had concomitant nasal pathology also showed improvement, leukotriene synthesis inhibitors were used as adjuvant therapy in the management of patients with rhinitis, sinusitis and nasal polyposis. Preliminary studies have demonstrated improvements in nasal airflow and reduced recurrence of nasal polyps as noted by endoscopy and imaging studies. Leukotriene synthesis inhibitors therefore appear to be a novel treatment modality for patients with rhinitis, sinusitis and nasal polyps when used as adjunctive therapy.