Induced sputum eicosanoids during aspirin bronchial challenge of asthmatic patients with aspirin hypersensitivity

Background: Altered metabolism of eicosanoids is a characteristic finding in aspirin-exacerbated respiratory disease (AERD). Bronchial challenge with lysylaspirin can be used as a confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. Objectives: To investigate the influence of inhaled lysyl-aspirin on sputum supernatant concentration of eicosanoids during the bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal anti-inflammatory drugs were compared with aspirin-tolerant asthmatic controls. Methods: Induced sputum was collected before and following bronchial challenge with lysyl-aspirin. Sputum differential cell count and sputum supernatant concentrations of selected lipoxygenases products: 5-,12-,15-hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4, 11-dehydro-thromboxane B2, and prostaglandins E2, D2, and Fa, and their metabolites, were measured using validated methods of chromatography mass spectrometry. Results: Aspirin precipitated bronchoconstriction in all AERD subjects, but in none of the aspirin-tolerant asthmatics. Phenotypes of asthma based on the sputum cytology did not differ between the groups. Baseline sputum eosinophilia correlated with a higher leukotriene D4 (LTD4) and leukotriene E4 (LTE4) concentrations. LTC4, PGE2, and 11-dehydro-TXB2 did not differ between the groups, but levels of LTD4, LTE4, and PGD2 were significantly higher in AERD group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4 decreased in AERD subjects only. Conclusions: During the bronchial challenge, decrease in PGE2 and its metabolite is accompanied by a surge in bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to a low dose of aspirin.