Induced sputum supernatant eicosanoids during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls

Abstract

Background: Altered eicosanoid metabolismis a characteristic finding of aspirin induced asthma (AIA). Oral aspirin challenge is confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. Objectives: The influence of aspirin on sputum supernatant concentration of eicosanoids during the oral challenge test was studied, using chromatography-mass spectrometry measurements. Methods: Induced sputum was collected before and following oral aspirin challenge. Sputum differential cell count and sputum supernatant concentrations of prostaglandin E 2 (PGE 2 ) was measured. Results: Aspirin precipitated bronchoconstriction was reported in all AIA (n=15) subjects, but in none of HC (n=13) and ATA (n=15). AIA was characterized by the dominance of the eosinophilic airway inflammation, whereas the paucigranulocytic phenotype was most frequent in HC. At baseline, mean induced sputum supernatant level of PGE 2 did not differ between the groups. Following the challenge, PGE 2 decreased in asthmatics patients independent of aspirin hypersensitivity (AIA p=0.002; ATAp=0.02), but not in HC (p=0.07). Cumulative doses of aspirin or the duration of the challenge had no effect on the magnitude of the PGE 2 alterations. Conclusions: During the oral aspirin challenge, PGE 2 decreases significantly in asthmatics as compared to healthy ones. The results support the theory on the inhibition of PGE 2 biosynthesis as a trigger for bronchoconstriction mediated by cysteinyl leukotrienes in AIA.