Biosynthesis of cysteinyl-leucotrienes in aspirin-intolerant asthma

Sanak, M. and Sampson, A. P. (1999) Biosynthesis of cysteinyl-leucotrienes in aspirin-intolerant asthma. Clinical and Experimental Allergy, 29 (3), 306-313. (doi:10.1046/j.1365-2222.1999.00443.x).

Abstract

Most medical concern over the worldwide use of aspirin (acetylsalicylic acid), the leading over-the-counter analgesic in many countries, has focused on the rare occurrences of Reye's syndrome (encephalopathy with hepatic failure) and gastric erosion in patients taking large aspirin doses for rheumatoid arthritis. Hypersensitivity to aspirin manifested as severe respiratory dysfunction has been relatively disregarded. Adverse respiratory reactions to aspirin and other non-steroidal anti-inflammatory drugs (NSAID) are well documented in the literature, but frequently overlooked in asthmatic patients. Only 3–5% of adult asthmatics have a clinical history of NSAID hypersensitivity, but this rises to about 20% when asthmatics are challenged with NSAIDs in the laboratory.

Aspirin-intolerant asthma (AIA) is a syndrome with features reminiscent of a protracted viral respiratory infection. Classic symptoms of chronic rhinoconjunctivitis, nasal polyps and bronchial asthma typically define the syndrome [ 1]. The onset of AIA is insidious, with a peak incidence around 35 years of age, although AIA has been observed in adolescents. AIA usually persists for life, but in some cases the disease is self-limiting. In AIA patients, acute hypersensitivity reactions to NSAIDs are superimposed upon a background of chronic, severe asthma. Acute asthma attacks may be precipitated following ingestion of even small doses of aspirin (frequently less than 80 mg), often accompanied by congestion of the conjunctiva and nasal mucosa. AIA patients usually have adverse reactions to a wide range of NSAIDs. Bronchoconstriction may be severe and life-threatening, requiring hospital admission and sometimes mechanical ventilation. Up to 25% of hospital admissions for acute asthma requiring emergency mechanical ventilation may be caused by NSAID ingestion. Aspirin and other NSAIDs must be avoided by AIA patients, although the atypical NSAID paracetamol and the new cyclooxygenase-2-selective NSAIDs (e.g. meloxicam) may be better tolerated. Even in the absence of exposure to NSAIDs, the underlying severity of chronic asthma necessitates oral corticosteroid therapy in 50% of AIA patients. Desensitization, in which incremental oral doses of aspirin extinguish adverse reactions as long as the drug is regularly ingested, may alleviate clinical symptoms, especially rhinosinusitis. This review will discuss the evidence for a fundamental abnormality in cysteinyl-leukotriene synthesis in AIA patients, which provides a rationale for the clinical use of leucotriene modifier (LM) drugs in these patients.

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Contributors

Author: A. P. Sampson

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