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Urinary leukotriene E4 and prostaglandin D2 metabolites increase in adult and childhood severe asthma characterized by type-2 inflammation

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Title: Urinary leukotriene E4 and prostaglandin D2 metabolites increase in adult and childhood severe asthma characterized by type-2 inflammation
Authors: Kolmert, J
Gómez, C
Balgoma, D
Sjödin, M
Bood, J
Konradsen, JR
Ericsson, M
Thörngren, J-O
James, A
Mikus, M
Sousa, AR
Riley, JH
Bates, S
Bakke, PS
Pandis, I
Caruso, M
Chanez, P
Fowler, SJ
Geiser, T
Howarth, P
Horváth, I
Krug, N
Montuschi, P
Sanak, M
Behndig, A
Shaw, DE
Knowles, RG
Holweg, CTJ
Wheelock, ÅM
Dahlén, B
Nordlund, B
Alving, K
Hedlin, G
Chung, KF
Adcock, IM
Sterk, PJ
Djukanovic, R
Dahlén, S-E
Wheelock, CE
U-BIOPRED Study Group
Item Type: Journal Article
Abstract: RATIONALE: New approaches are needed to guide personalized treatment of asthma. OBJECTIVE: To test if urinary eicosanoid metabolites can direct asthma phenotyping. METHODS: Urinary metabolites of prostaglandins (PGs), cysteinyl-leukotrienes (LTs) and isoprostanes were quantified in the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy controls (HC). Validation was performed internally in 302 SA subjects followed-up after 12-18 months, and externally in 95 adolescents with asthma. MEASUREMENT AND MAIN RESULTS: Metabolite levels in HC were unrelated to age, BMI and sex, except for the PGE2-pathway. Eicosanoid levels were generally greater in MMA relative to HC, with further elevations in SA. However, PGE2-metabolite levels were either the same or lower in male non-smoking asthmatics as in HC. Metabolite levels were unchanged in asthmatics adherent to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas SA treated with omalizumab had lower levels of LTE4 and the PGD2 metabolite 2,3-dinor-11β-PGF2α. High levels of LTE4 and PGD2-metabolites were associated with lower lung-function, and increased levels of exhaled nitric oxide and eosinophil markers in blood, sputum and urine in U-BIOPRED and in adolescents with asthma. These type-2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study, and found to be as sensitive to detect T2 inflammation as the established biomarkers. CONCLUSIONS: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new non-invasive approach for molecular phenotyping of adult and adolescent asthma. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Issue Date: 15-Jul-2020
Date of Acceptance: 10-Jul-2020
URI: http://hdl.handle.net/10044/1/83646
DOI: 10.1164/rccm.201909-1869OC
ISSN: 1073-449X
Publisher: American Thoracic Society
Start Page: 37
End Page: 53
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 203
Issue: 1
Copyright Statement: © 2020 by the American Thoracic Society. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage and reprints, please contact Diane Gern (dgern@thoracic.org).
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 115010
Keywords: U-BIOPRED
mass spectrometry
severe asthma
type 2 inflammation
urinary eicosanoid metabolites
Adult
Asthma
Biomarkers
Female
Humans
Inflammation
Leukotriene E4
Male
Middle Aged
Prostaglandins
U-BIOPRED Study Group, on behalf of the U-BIOPRED Study Group
Swedish Search
Type-2 inflammation
U-BIOPRED
severe asthma
urinary eicosanoid metabolites
11 Medical and Health Sciences
Respiratory System
Publication Status: Published
Conference Place: United States
Online Publication Date: 2020-07-15
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons