The role of aspirin desensitization followed by oral aspirin therapy in managing patients with aspirin-exacerbated respiratory disease: A Work Group Report from the Rhinitis, Rhinosinusitis and Ocular Allergy Committee of the American Academy of Allergy, Asthma & Immunology

Abstract

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the cycloxgenase-1 enzyme. Patients with AERD on average have more severe respiratory disease compared with patients with chronic rhinosinusitis with nasal polyps and/or asthma alone. Although patients with AERD traditionally develop significant upper and lower respiratory tract symptoms on ingestion of cycloxgenase-1 inhibitors, most of these same patients report clinical benefit when desensitized to aspirin and maintained on daily aspirin therapy. This Work Group Report provides a comprehensive review of aspirin challenges, aspirin desensitizations, and maintenance aspirin therapy in patients with AERD. Identification of appropriate candidates, indications and contraindications, medical and surgical optimization strategies, protocols, medical management during the desensitization, and recommendations for maintenance aspirin therapy following desensitization are reviewed. Also included is a summary of studies evaluating the clinical efficacy of aspirin therapy after desensitization as well as a discussion on the possible cellular and molecular mechanisms explaining how this therapy provides unique benefit to patients with AERD.

Keywords: AERD; Aspirin-exacerbated respiratory disease; NSAID-exacerbated respiratory disease; Samter triad; aspirin desensitization.

FIG 1.

Algorithm for evaluating patients for an aspirin desensitization followed by maintenance aspirin therapy.

FIG 2.

Arachidonic acid metabolism is dysregulated in AERD. Compared with aspirin-tolerant patients, patients with AERD at baseline have elevated levels of CysLTs (LTC₄, LTD₄, LTE₄) and PGD₂ that mediate bronchospasm, vascular leak, inflammatory cell recruitment, and enhanced mucus production. In contrast, levels of PGE₂, which has anti-inflammatory properties and can induce bronchodilation, are reduced in patients with AERD. Although the precise mechanism of benefit from aspirin therapy is unclear, the effects of PGD₂ and CysLTs are dominant components. During an aspirin desensitization, urinary levels of PGD₂ further increase but later decrease while on high-dose aspirin therapy. In contrast, urinary levels of CysLTs have not been found to decrease while on high-dose aspirin therapy, but expression of the CysLT receptor 1 (CysLTR1) has been shown to be reduced. CRTH2, Chemoattractant receptor-homologous molecule expressed on T_H2 cells; CysLTR2, CysLT receptor 2; CysLTR3, CystLT receptor 3; DP1, prostaglandin D₂ receptor 1; EP2, prostaglandin E₂ receptor 2; EP4, prostaglandin E₂ receptor 4; TP, thromboxane receptor; TXA₂, thromboxane A₂.