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Increase in urinary leukotriene B 4 glucuronide concentration in patients with aspirin‐intolerant asthma after intravenous aspirin challenge
Author(s) -
Mita H.,
Higashi N.,
Taniguchi M.,
Higashi A.,
Akiyama K.
Publication year - 2004
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2004.02034.x
Subject(s) - aspirin , leukotriene e4 , urinary system , urine , asthma , creatinine , leukotriene b4 , leukotriene , chemistry , medicine , provocation test , endocrinology , chromatography , pathology , alternative medicine , inflammation
Summary Background Aspirin challenge of aspirin‐intolerant asthma (AIA) patients causes a significant increase in leukotriene E 4 (LTE 4 ) concentration in urine. However, knowledge on leukotriene B 4 (LTB 4 ) generation in patients with AIA is insufficient. Recent research has demonstrated that exogenously administered LTB 4 is excreted as glucuronide into the urine in human healthy subjects. Objective The purpose of this study is to estimate urinary LTB 4 glucuronide (LTBG) concentration in the clinically stable condition in healthy subjects and asthmatic patients and to investigate changes in urinary LTBG concentration in patients with AIA after aspirin challenge. Methods A provocation test was performed by intravenous aspirin challenge. After urine was hydrolysed by β‐glucuronidase, the fraction containing LTB 4 was purified by high‐performance liquid chromatography and LTB 4 concentration was quantified by enzyme immunoassay. Urinary LTBG concentration was calculated as the difference between the concentration obtained with hydrolysis and that without hydrolysis. Results (1) After hydrolysis, the presence of urinary LTB 4 was verified by gas chromatography‐mass spectrometry‐selected ion monitoring. (2) The urinary LTBG concentration was significantly higher in the asthmatic patients than in the healthy subjects (median, 5.37 pg/mg creatinine [range 1.2–13] vs. 3.32 pg/mg creatinine [range, 0.14–10.5], P =0.0159). (3) The patients with AIA ( n =7), but not those with aspirin‐tolerant asthma ( n =6), showed significant increases in LTBG and LTE 4 excretions after aspirin challenge. (4) When the concentrations after aspirin challenge were analysed simultaneously, a significant linear correlation was observed between urinary LTBG concentration and urinary LTE 4 concentration in patients with AIA (Spearman's rank correlation test, r =0.817, P =0.0003). Conclusion LTBG is present in human urine, albeit at a concentration lower than urinary LTE 4 . In addition to a marked increase in cysteinyl‐leukotriene production, aspirin challenge induced LTB 4 production in AIA patients.