Is montelukast indicated for treatment of chronic rhinosinusitis with polyposis?

BACKGROUND Cysteinyl leukotrienes (CysLT) are a class of inflammatory mediators synthesized by eosinophils and mast cells through the breakdown of arachidonic acid. They are known to play a key role in the molecular pathophysiology of asthma and chronic rhinosinusitis (CRS), promoting bronchoconstriction, mucus production, edema, and chemotaxis of neutrophils and eosinophils. Indeed, upregulation of CysLT receptors and overproduction of CysLTs has been demonstrated in asthma, allergic rhinitis, and CRS with nasal polyposis (CRSwNP), particularly in patients with Samter’s triad, and reversal of this upregulation has been observed following aspirin salicylic acid (ASA) desensitization. Several CysLT inhibitors have been developed within the past 20 years, and due to their “corticosteroid sparing” effects are commonly prescribed adjunctive therapeutics for asthma, allergic rhinitis, and exercise-induced bronchoconstriction. Montelukast (Singulair, Merck; Whitehouse Station, NJ), zafirlukast (Accolate, Vanticon, Accoleit; Sellect Chemicals LLC, Houston, TX, and AstraZeneca; Wilmington, DE) and pranlukast (Ultair, Cayman Chemical; Ann Arbor, MI) act as competitive antagonists at the CysLT1 receptor. Notably, upregulation of a separate CysLT receptor (CysLT2) has been observed in nasal mucosa of patients with CRSwNP; however, Montelukast, Pranlukast, and Zafirlukast all lack antagonist action at this receptor. Zileuton (Zyflo CR, Cary, NC, Cornerstone Therapeutics) is a selective 5-lipoxygenase enzyme inhibitor, preventing CysLT synthesis. A recent discovery of another class of antileukotrienes, termed 5-lipoxygenase activating protein (FLAP) inhibitors, may allow for potential future drug development. Although they are commonly utilized as adjunctive treatments, there is a paucity of evidence regarding efficacy of CysLT inhibitor treatment for CRSwNP. Therefore, we asked the question: Is Montelukast indicated for treatment of CRSwNP?