An update on the management of aspirin-exacerbated respiratory disease

Abstract

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD.

Which Factors Associated With Activated Eosinophils Contribute to the Pathogenesis of Aspirin-Exacerbated Respiratory Disease?

“…Aspirin-exacerbated respiratory disease (AERD) is characterized by hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), asthma and chronic rhinosinusitis (CRS) with nasal polyps (NPs) 1. Overproduction of cysteinyl leukotrienes (cysLTs) is a hallmark of AERD in the pathogenic mechanisms.…”

NSAID-Exacerbated Respiratory Disease (NERD): From Pathogenesis to Improved Care

“…Bronchial challenge with lysine-aspirin is safer and quicker, but shows lower sensitivity than the oral test. Nasal challenge is recommended for patients with predominant nasal symptoms, but the sensitivity is lower ( Lee et al., 2018a ; Kowalski et al., 2019 ). The EAACI recommended the oral challenge protocol with starting 20-40 mg of aspirin and gradually increasing the dose at 2 hour intervals.…”

“…In the COX and LOX pathways, AA is metabolized to CysLTs (mostly LTE 4 , via 5-lipoxygenase [5-LO] and LTC 4 synthase [LTC4S]), prostaglandin (PG) pathway (PGE 2 , PGF 2 , PGI 2 and PGD 2 ) and thromboxanes (TBX) A 2 by PG synthase and TBX synthase (Szczeklik, 1990), where enhanced synthesis of CysLTs synthesis with reduced level of PGE 2 is a major finding in NERD (Pham et al, 2016;Pham et al, 2017;Lee et al, 2018a;Yin et al, 2020). NERD patients have higher levels of CysLTs (especially LTE 4 ) mainly derived from various inflammatory cells, including neutrophils, monocytes, and basophils, eosinophils and mast cells, which further increases after ASA/NSAID exposure compared to asthmatic patients with ASA/NSAID tolerance (ATA).…”

“…NERD is a major phenotype among cross-intolerant categories of NSAID hypersensitivity and had been called ASA-induced asthma, ASA-intolerant asthma, ASA-sensitive asthma; however, NERD and ASA-exacerbated respiratory disease (AERD) are commonly used ( Sánchez-Borges, 2019 ). The prevalence of NERD is reported to be 5.5% to 12.4% in the general population ( Lee et al., 2018a ; Chu et al., 2019 ; Taniguchi et al., 2019 ), 7.1% among adult asthmatics and 14.9% among severe asthmatics ( Rajan et al., 2015 ), while it rarely occurs in children ( Taniguchi et al., 2019 ). No relationships were found with family history or NSAID administration history ( Kowalski et al., 2011 ; Taniguchi et al., 2019 ).…”

Update on the Management of Nonsteroidal Anti-Inflammatory Drug Hypersensitivity

“…Most NSAIDs have nonselective inhibitions of COX-1 enzymes. They interfere with arachidonic acid metabolism, leading to blockage of prostaglandin synthesis and up-regulation of the leukotriene pathway that contributes to various presentations of NSAID hypersensitivity reactions 7. NSAIDs that possess predominant inhibition of COX-1 enzymes, such as indomethacin, naproxen, and diclofenac, have higher rates of hypersensitivity reactions, while weak COX-1 inhibitors and selective COX-2 inhibitors are often better tolerated with a lower probability of hypersensitivity reactions.…”