IngentaConnect Increase in urinary leukotriene B4 glucuronide concentration in p...

Abstract:

Summary Background

Aspirin challenge of aspirin-intolerant asthma (AIA) patients causes a significant increase in leukotriene E₄ (LTE₄) concentration in urine. However, knowledge on leukotriene B₄ (LTB₄) generation in patients with AIA is insufficient. Recent research has demonstrated that exogenously administered LTB₄ is excreted as glucuronide into the urine in human healthy subjects. Objective

The purpose of this study is to estimate urinary LTB₄ 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 beta

-glucuronidase, the fraction containing LTB₄ was purified by high-performance liquid chromatography and LTB₄ 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 LTB₄ 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 LTE₄ 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 LTE₄ 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 LTE₄. In addition to a marked increase in cysteinyl-leukotriene production, aspirin challenge induced LTB₄ production in AIA patients.

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Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge

Increase in urinary leukotriene B₄ glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge