Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type-2 Inflammation.

Kolmert, Johan; Gómez, Cristina; Balgoma, David; Sjödin, Marcus; Bood, Johan; Konradsen, Jon R; Ericsson, Magnus; Thörngren, John-Olof; James, Anna; Mikus, Maria; Sousa, Ana R; Riley, John H; Bates, Stewart; Bakke, Per S; Pandis, Ioannis; Caruso, Massimo; Chanez, Pascal; Fowler, Stephen J; Geiser, Thomas; Howarth, Peter; ... (2021). Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type-2 Inflammation. American journal of respiratory and critical care medicine, 203(1), pp. 37-53. American Lung Association 10.1164/rccm.201909-1869OC

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Geiser, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1073-449X

Publisher:

American Lung Association

Language:

English

Submitter:

Heidi Lobsiger

Date Deposited:

16 Jul 2020 12:07

Last Modified:

04 Jan 2021 01:31

Publisher DOI:

10.1164/rccm.201909-1869OC

PubMed ID:

32667261

Uncontrolled Keywords:

Swedish Search Type-2 inflammation U-BIOPRED severe asthma urinary eicosanoid metabolites

URI:

https://boris.unibe.ch/id/eprint/145227

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