Abstract

Background: Diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E4 is elevated in aspirin-intolerant asthma.

Objective: New biomarkers of aspirin-intolerance were investigated by comparing basal levels of cysteinyl-leukotrienes and leukotriene B4 in saliva, sputum, and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators.

Methods: Induced sputum, saliva, urine and blood were obtained at baseline in 21 subjects with asthma. At a separate visit, eleven subjects showed a positive response to lysine-aspirin inhalation whereas ten were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of cysteinyl-leukotrienes and leukotriene B4 and the prostaglandin D2 metabolite 9α,11β-prostaglandin F2 were performed and the fraction of exhaled nitric oxide was measured.

Results: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of cysteinyl-leukotrienes in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in leukotriene B4 between the groups. Levels of urinary leukotriene E4, and 9α,11β-prostaglandin F2 increased after aspirin provocation, whereas leukotriene levels in saliva and ex vivo stimulated blood were not increased post challenge.

Conclusion: The findings support a global and specific exaggeration of cysteinyl-leukotriene production in aspirin-intolerant asthma. Measurement of cysteinyl-leukotrienes in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.