The mechanisms of aspirin-intolerant asthma and its management

Abstract

Aspirin is one of the most widely used medications in the world. Adverse effects related to aspirin use were described almost concurrently with its first use. The most common side effects are gastrointestinal and renal, but adverse respiratory effects are not uncommon, and approximately 10% of adult asthmatics are aspirin intolerant. Many of these patients present with the so-called aspirin triad of aspirin sensitivity, chronic rhinosinusitis with associated nasal polyposis, and severe asthma. This paper provides a review of recent investigations into the pathogenesis of this process, which have furthered our understanding of the mechanisms and management of aspirin-induced asthma.

Medical and Surgical Considerations in Patients with Samter's Triad

“…Patients usually develop rhinologic symptoms before being diagnosed with asthma, while aspirin sensitivity follows asthma onset. 10 Patients rarely note symptoms before the second decade of life, with symptoms peaking in the third decade. 27 Typically, acute asthma exacerbation and severe rhinorrhea will occur within 3 hours of ingestion of aspirin.…”

“…29 History alone is less reliable than objective response to challenge testing. 10 Challenge with oral aspirin, 26 oral lysine-aspirin, 30 endonasal lysine-aspirin, 31 and in vitro measurement of eicosanoid release from mixed leukocyte cultures 32 have been described as sensitive methods of diagnosing aspirin sensitivity. Given the relationship between LT and ST, inhibition with LT receptor blockers (e.g., montelukast and zafirlukast) and 5-lipoxygenase inhibitors (e.g., zileuton) have been studied with mixed results.…”

“…35 Aspirin DS is contraindicated for patients with unstable asthma, asthma nonresponsive to corticosteroid therapy, patients on B-blockers, and patients with potential compliance problems. 10 Antihistamines, cromolyn sodium, and inhaled B-adrenergic medications should be discontinued before initiating DS, although theophylline and corticosteroids may be continued. 9 DS may be maintained for as long as the patient continues to take maintenance aspirin dosing on a q.d.…”

“…8 Although there is no clear evidence of IgE-mediated reaction, 9 certain patients can have anaphylactoid reactions to aspirin. 10 Aspirin diverts arachidonic acid metabolism by blocking cyclooxygenase (COX) activity, thereby diverting arachidonic acid to the lipoxygenase pathway. This results in decreased production of prostaglandins (PG), including anti-inflammatory PGE 2 produced by COX-1, and increased production of proinflammatory cysteinyl leukotrienes (LT).…”

Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics

“…However, these corpuscles can use LTA 4 released from neighboring cells through transcellular metabolism (99). Increased expression of LTC4S was observed in eosinophils and macrophages derived from lung tissue of aspirinintolerant asthmatics (100,101). Furthermore, neutrophils derived from patients with acute myelocytic leukemia show an aberrant expression profile of LTC4S (102).…”