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Lookup NU author(s): Dr James Lordan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The authors 2025. Background ∼5–10% of patients with asthma have severe disease. A proportion remain symptomatic despite suppression of T2-related inflammation but what drives persistent symptoms remains unclear. Eicosanoids exert a functional role in pulmonary inflammation. We explored the relationship between urinary eicosanoids, asthma symptoms, obesity and T2-biomarker status. Methods Urine was sampled during a randomised controlled trial assessing corticosteroid optimisation using T2-biomarker directed care at scheduled study visits (n=728) and at exacerbation (n=103). Urine eicosanoid concentrations were measured by mass spectrometry, then log2-transformed, z-scored and concatenated by biosynthetic pathway generating six pathway scores. Results were stratified by T2 status (T2-low: exhaled nitric oxide fraction (FENO) <20 ppb and blood eosinophil count (BEC) <0.15×109 cells·L−1; versus T2-high: FENO ⩾20 ppb and BEC ⩾0.15×109 cells·L−1), symptoms (symptom-low: Asthma Control Questionnaire-7 (ACQ-7) <1.5; versus symptom-high: ACQ-7 ⩾1.5) and obesity. Results Isoprostane (pathway score p=0.02) and thromboxane (pathway score p=0.04) levels were higher in symptom-high versus symptom-low, T2-low participants. Isoprostane levels were greater in symptom-high versus symptom-low participants, irrespective of T2 status (pathway score p=0.01). Cysteinyl-leukotriene E4 levels (LTE4) were elevated in T2-high versus T2-low participants (pathway score p=0.0007), irrespective of symptoms. Corticosteroid exposure, obesity and exacerbations were not associated with increased eicosanoid levels (p⩾0.05). Conclusion Raised urinary eicosanoid levels of isoprostanes and thromboxanes were associated with increased symptoms in T2-low severe asthma. Elevated excretion of these metabolites in T2-low participants.
Author(s): Eastwood MC, Busby J, Kolmert J, Zurita J, Dahlen S-E, McDowell PJ, Bradley J, Jackson D, Pavord I, Djukanovic R, Arron J, Bradding P, Brightling C, Chaudhuri R, Cowan D, Fowler S, Hardman TC, Holweg C, Lordan J, Mansur A, Robinson D, Wheelock CE, Heaney L
Publication type: Article
Publication status: Published
Journal: ERJ Open Research
Year: 2025
Volume: 11
Issue: 4
Online publication date: 26/08/2025
Acceptance date: 15/01/2025
Date deposited: 01/10/2025
ISSN (electronic): 2312-0541
Publisher: European Respiratory Society
URL: https://doi.org/10.1183/23120541.01089-2024
DOI: 10.1183/23120541.01089-2024
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