Aspirin sensitivity and desensitization for asthma and sinusitis

Abstract

NSAIDs-including aspirin (ASA)-that inhibit cyclooxygenase (COX)-1 induce nonallergic hypersensitivity reactions consisting of attacks of rhinitis and asthma. Such reactions occur exclusively in a subset of asthmatic patients who also have underlying nasal polyps and chronic hyperplastic eosinophilic sinusitis. We now refer to their underlying inflammatory disease of the entire respiratory tract as aspirin-exacerbated respiratory disease. This review focuses on descriptions of these patients; methods available to diagnose ASA-exacerbated respiratory disease; the unique ability of all NSAIDs that inhibit COX-1 to cross-react with ASA; lack of cross-reactivity with selective COX-2 inhibitors; an update on pathogenesis; and current thoughts about treatment, including ASA desensitization and daily ingestion of ASA itself.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…The NSAID sensitivity often manifests as ASA intolerance, and the disorder is now generally referred to as aspirin (or NSAID)-exacerbated respiratory disease (AERD). [947][948][949] Prevalence rates of AERD in the general population have been estimated at 0.6% to 2.5% and in CRSwNP patients at 9.7%. 950,951 An incomplete triad might be observed in patients with recurrent nasal polyposis and asthma who do not yet report adverse reactions to NSAIDs.…”

Current management of aspirin‐exacerbated respiratory disease

“…8,9 Nasal therapy with increasing doses of lysine aspirin following a positive nasal challenge has been used in our department for several years. 10 Most patients can reach a total dose equivalent to 60-75mg aspirin in the nose, with benefit in the majority and a better safety profile than with oral aspirin.…”

Concurrent coxibs and anti-platelet therapy unmasks aspirin-exacerbated respiratory disease

“…The central mechanism was regarded as the deprivation of PGE 2 as a consequence of COX-1 inhibition, which would lead to an even more increased local and systemic generation of cysteinyl leukotrienes (LT). The overproduction of cysteinyl LT, due to upregulation of LTC 4 synthase and/or cysteinyl LT receptors in the airways, the hallmark of the disease, occurs at baseline as well, although at a much lower degree than after aspirin/NSAIDs intake [2].After the introduction of the selective COX-2 inhibitors, casually referred to as coxibs, several well-designed studies reported the excellent safety profile of these new NSAIDs in patients with AERD [3,4]. Nevertheless, shortly afterwards, as the use of coxibs extended, so did the number of case reports warning the clinicians that some AERD patients may not tolerate coxibs [5,6].…”

“…The central mechanism was regarded as the deprivation of PGE 2 as a consequence of COX-1 inhibition, which would lead to an even more increased local and systemic generation of cysteinyl leukotrienes (LT). The overproduction of cysteinyl LT, due to upregulation of LTC 4 synthase and/or cysteinyl LT receptors in the airways, the hallmark of the disease, occurs at baseline as well, although at a much lower degree than after aspirin/NSAIDs intake [2].…”

“…Even more so, the patient tolerated low doses of ASA and only had bronchospasm when challenged with coxibs (except of course for the original episode with dektetoprofen, not surprising a posteriori), while usually this occurs the other way around, due to accidental self-administration of over-the-counter NSAIDs. It appears that he tolerated his chronically decreased PGE 2 production due to the daily treatment with low doses of ASA, but the equilibrium was disrupted when the COX-2 inhibitors additionally diminished the biosynthesis of PGE 2 , leaving the lower airway without any protection against cysteinyl LT [2]. Maybe if ASA was suspended, this patient might tolerate coxibs; nevertheless, we consider that this case brings us a small step closer to understanding the complex mechanisms of aspirin hypersensitivity, which still remain unclear despite over 30 years of intensive research.…”