Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma

• Published in: Thorax Vol. 63; no. 12; pp. 1076 - 1082
• Main Authors: Gaber, F, Daham, K, Higashi, A, Higashi, N, Gülich, A, Delin, I, James, A, Skedinger, M, Gyllfors, P, Nord, M, Dahlén, S-E, Kumlin, M, Dahlén, B
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.12.2008; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Aspirin; Aspirin - adverse effects; Asthma; Asthma - chemically induced; Biological and medical sciences; Biomarkers - analysis; Cardiology. Vascular system; Chronic obstructive pulmonary disease, asthma; Cysteine - analysis; Dinoprost - metabolism; Drug dosages; Drug Hypersensitivity - etiology; Drug Hypersensitivity - metabolism; Female; Humans; Immunology; Leukotriene B4 - analysis; Leukotrienes - analysis; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Nitric oxide; Pneumology; Saliva - chemistry; Spirometry; Sputum - chemistry; Urine; Uteroglobin - analysis; Prostaglandin-endoperoxide synthase; Biological fluid; Acetylsalicylic acid; Blood; Bronchus disease; Anesthesia; Obstructive pulmonary disease; Salicylates; Cardiology; Human; Urine; Lung disease; Enzyme; Respiratory disease; Enzyme inhibitor; Patient; Antiplatelet agent; Asthma; Non steroidal antiinflammatory agent; Leukotriene; Analgesic; Sputum; Antipyretic; Level; Oxidoreductases; Circulatory system; Saliva
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2008.101196

Background:A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E4 (LTE4) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B4 (LTB4) 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 from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB4 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 CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB4 levels between the groups. Levels of urinary LTE4 and 9α,11β-prostaglandin F2 increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase.Conclusion:These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.