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Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive. Pretreatment with medications that inhibit the leukotriene pathway decreases the severity of clinical reactions, which points to the involvement of cysteinyl leukotrienes (cysLTs) in the pathogenesis of these aspirin\u2010induced reactions. Furthermore, studies of aspirin challenges in carefully\u2010phenotyped patients with AERD have confirmed that both proinflammatory lipid mediators, predominantly cysLTs and prostaglandin (PG) D<jats:sub>2<\/jats:sub>, and the influx of effector cells to the respiratory tissue, contribute to symptom development during aspirin\u2010induced reactions. Mast cells, which have been identified as the major cellular source of cysLTs and PGD<jats:sub>2<\/jats:sub>, are likely to be major participants in the acute reactions, and are an attractive target for future pharmacotherapies in AERD. Although several recent studies support the role of platelets as inflammatory effector cells and as a source of cysLT overproduction in AERD, it is not yet clear whether platelet activation plays a direct role in the development of the aspirin\u2010induced reactions. To further our understanding of the pathogenesis of aspirin\u2010induced reactions in AERD, and to broaden the pharmacotherapeutic options available to these patients, additional investigations with targeted clinical trials will be required.<\/jats:p>","DOI":"10.1016\/j.wjorl.2018.08.001","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T16:36:41Z","timestamp":1536165401000},"page":"162-168","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"title":["Pathogenesis of NSAID\u2010induced reactions in aspirin\u2010exacerbated respiratory disease"],"prefix":"10.1002","volume":"4","author":[{"given":"Tanya M.","family":"Laidlaw","sequence":"first","affiliation":[{"name":"Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy Boston MA USA"},{"name":"Harvard Medical School Boston MA 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