Aspirin-induced asthma: Advances in pathogenesis and management,☆☆

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Abstract

In some patients with asthma, aspirin (ASA) and all nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase enzymes (cyclooxygenase-1 and -2) precipitate asthmatic attacks and naso-ocular reactions. This distinct clinical syndrome, called aspirin-induced asthma (AIA), is characterized by a typical sequence of symptoms, intense eosinophilic inflammation of nasal and bronchial tissues, combined with overproduction of cysteinyl-leukotrienes (Cys-LTs). At baseline, cys-LT urinary excretion is augmented, and ASA administration leads to its further temporary increase. After ASA challenge, cys-LTs are released into nasal and bronchial secretions and can be collected in the urine. LTC 4 synthase, the terminal enzyme for cys-LT production, is markedly overexpressed in eosinophils and mast cells from bronchial biopsy specimens of most patients with AIA. An allelic variant of LTC 4 synthase that enhances enzyme transcription is associated with AIA. Avoiding ASA and nonsteroidal anti-inflammatory drugs does not prevent progression of the inflammatory disease. Corticosteroids continue to be the mainstay of therapy, and anti-LT drugs are also indicated for treatment of the underlying disease. After ASA desensitization, daily ingestion of high doses of ASA reduces inflammatory mucosal disease symptoms, particularly in the nasal passages, in most patients with AIA. (J Allergy Clin Immunol 1999;104:5-13.)

Section snippets

DEFINITION AND CLINICAL PRESENTATION

AIA, also called aspirin-sensitive or aspirin-intolerant asthma, is an aggressive mucosal inflammatory disease combined with precipitation of asthma and rhinitis attacks after ingestion of ASA and most nonsteroidal anti-inflammatory drugs (NSAIDs). 4, 5, 6, 7 AIA affects about 10% of adults with asthma, more often women than men. 8 Familial occurrence is quite rare, and the disease is infrequently found in asthmatic children. 8

In most patients symptoms of rhinitis first occur during the third

The futile search for an allergic mechanism

Clinical symptoms precipitated by ASA or NSAIDs in patients with AIA are reminiscent of immediate hypersensitivity reactions. Therefore an underlying antigen-antibody mechanism has been suggested and investigated. However, skin test responses with ASA-lysine have been negative, and numerous attempts to demonstrate specific antibodies against ASA or its derivatives were unsuccessful. 14 Neither differences in bioavailability of ASA nor the formation of salicylic acid seem to contribute to

PREVENTION AND TREATMENT

The general rules concerning treatment of AIA do not differ from the published guidelines on the management of asthma. Most patients with AIA have moderate or severe persistent asthma. However, patients with AIA whose sinusitis is in remission may have mild asthma. These observations were recently confirmed by a multicenter study performed by participants of the European Network on Aspirin-Induced Asthma. Among 365 patients with AIA in the European Network on Aspirin-Induced Asthma study, 65

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    Reprint requests: Donald D. Stevenson, MD, Scripps Clinic and The Scripps Research Institute, 10666 N Torrey Pines Rd, La Jolla, CA 92037.

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