Aspirin causes bronchoconstriction in aspirin-intolerant asthma (AIA) patients by triggering cysteinyl-leukotriene (cys-LT) production, probably by removing PGE2-dependent inhibition. To investigate why aspirin does not cause bronchoconstriction in all individuals, we immunostained enzymes of the leukotriene and prostanoid pathways in bronchial biopsies from AIA patients, aspirin-tolerant asthma (ATA) patients, and normal (N) subjects. Counts of cells expressing the terminal enzyme for cys-LT synthesis, LTC4 synthase, were fivefold higher in AIA biopsies (11.5+/-2.2 cells/mm2, n = 10) than in ATA biopsies (2.2+/-0.7, n = 10; P = 0. 0006) and 18-fold higher than in N biopsies (0.6+/-0.4, n = 9; P = 0. 0002). Immunostaining for 5-lipoxygenase, its activating protein (FLAP), LTA4 hydrolase, cyclooxygenase (COX)-1, and COX-2 did not differ. Enhanced baseline cys-LT levels in bronchoalveolar lavage (BAL) fluid of AIA patients correlated uniquely with bronchial counts of LTC4 synthase+ cells (rho = 0.83, P = 0.01). Lysine-aspirin challenge released additional cys-LTs into BAL fluid in AIA patients (200+/-120 pg/ml, n = 8) but not in ATA patients (0. 7+/-5.1, n = 5; P = 0.007). Bronchial responsiveness to lysine-aspirin correlated exclusively with LTC4 synthase+ cell counts (rho = -0.63, P = 0.049, n = 10). Aspirin may remove PGE2-dependent suppression in all subjects, but only in AIA patients does increased bronchial expression of LTC4 synthase allow marked overproduction of cys-LTs leading to bronchoconstriction.

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Aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin‐induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin‐induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed.

Aspirin and other nonsteroidal anti-inflammatory drugs that inhibit COX-1 induce unique nonallergic reactions, consisting of attacks of rhinitis and asthma. These hypersensitivity reactions occur in a subset of asthmatic subjects, thus identifying them as having this exclusive clinical presentation. We refer to these patients as having aspirin-exacerbated respiratory disease, a disease process that produces devastating eosinophilic inflammation of both the upper and lower respiratory tracts. This review focuses on a description of patients with aspirin-exacerbated respiratory disease, methods available to diagnose their condition, the unique ability of all nonsteroidal anti-inflammatory drugs that inhibit COX-1 to cross-react with aspirin, an update on pathogenesis, and current thoughts about treatment.

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