Pathogenesis of NSAID-induced reactions in aspirin-exacerbated respiratory disease

Abstract

It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter's disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually involves nasal congestion, rhinorrhea, wheezing and bronchospasm. 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-induced reactions. Furthermore, studies of aspirin challenges in carefully-phenotyped patients with AERD have confirmed that both proinflammatory lipid mediators, predominantly cysLTs and prostaglandin (PG) D2, and the influx of effector cells to the respiratory tissue, contribute to symptom development during aspirin-induced reactions. Mast cells, which have been identified as the major cellular source of cysLTs and PGD2, 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-induced reactions. To further our understanding of the pathogenesis of aspirin-induced reactions in AERD, and to broaden the pharmacotherapeutic options available to these patients, additional investigations with targeted clinical trials will be required. Keywords: Aspirin-exacerbated respiratory disease (AERD), Nasal polyps, Samter's triad, Pathogenesis, Cysteinyl leukotrienes, Prostaglandins, Mast cell