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Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge.
Clin Exp Allergy. 2004 Aug; 34(8):1262-9.CE

Abstract

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.

Authors+Show Affiliations

Clinical Research Center, National Sagamihara Hospital, Kanagawa, Japan. h-mita@sagamihara-hosp.gr.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15298568

Citation

Mita, H, et al. "Increase in Urinary Leukotriene B4 Glucuronide Concentration in Patients With Aspirin-intolerant Asthma After Intravenous Aspirin Challenge." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 34, no. 8, 2004, pp. 1262-9.
Mita H, Higashi N, Taniguchi M, et al. Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge. Clin Exp Allergy. 2004;34(8):1262-9.
Mita, H., Higashi, N., Taniguchi, M., Higashi, A., & Akiyama, K. (2004). Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 34(8), 1262-9.
Mita H, et al. Increase in Urinary Leukotriene B4 Glucuronide Concentration in Patients With Aspirin-intolerant Asthma After Intravenous Aspirin Challenge. Clin Exp Allergy. 2004;34(8):1262-9. PubMed PMID: 15298568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge. AU - Mita,H, AU - Higashi,N, AU - Taniguchi,M, AU - Higashi,A, AU - Akiyama,K, PY - 2004/8/10/pubmed PY - 2004/12/21/medline PY - 2004/8/10/entrez SP - 1262 EP - 9 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin Exp Allergy VL - 34 IS - 8 N2 - 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. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/15298568/Increase_in_urinary_leukotriene_B4_glucuronide_concentration_in_patients_with_aspirin_intolerant_asthma_after_intravenous_aspirin_challenge_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=2004&volume=34&issue=8&spage=1262 DB - PRIME DP - Unbound Medicine ER -