Urinary eicosanoids in T2-low severe asthma: relationship with symptoms and exacerbation profile
Bibliographic record
Abstract
BACKGROUND: 5-10% of patients with asthma have severe disease. Many patients experience persistent symptoms despite being T2-low. Obesity is associated with increased asthma symptoms. Eicosanoids have well-described roles in the pathophysiology of asthma and may contribute to persistent symptoms in T2-low severe asthma. OBJECTIVE: To examine the relationship between urinary eicosanoids, asthma symptoms, obesity and T2-biomarkers in severe asthma. METHODS: Urine samples were collected during a randomized controlled trial assessing corticosteroid optimization using T2-biomarker directed care at scheduled study visits (n=728) and at exacerbation (n=103). Eicosanoid concentrations were quantified from urine samples using mass-spectrometry. Metabolite concentrations were log 2 -transformed, z-scored and concentrated by pathway to generate 6 pathway scores. Results were stratified by T2-biomarker status (T2-Low: fractional-exhaled nitric-oxide [FeNO]<20ppb AND blood eosinophil count [BEC]<0.15x10 9 cells/L) vs T2-high: (FeNO≥20ppb AND BEC≥0.15x10 9 cells/L), symptoms (symptom-low: Asthma control Questionnaire-7 (ACQ-7)<1.5)] vs symptom-high [ACQ-7≥1.5]), and obesity. RESULTS: The cysteinyl-leukotriene (CysLT) pathway score was elevated in T2-high versus T2-low participants (P=0.0007), regardless of symptom burden. The isoprostane pathway score was higher in symptom-high versus symptom-low participants, regardless of T2-status (P=0.01). Higher isoprostane (P=0.02) and thromboxane (P=0.04) pathway scores were associated with increased symptoms in T2-low participants. Corticosteroid exposure, obesity and exacerbations were not associated with raised pathway scores (P≥0.05). CONCLUSION: Thromboxane pathway metabolites were elevated in symptom-high/T2-low participants whereas isoprostane pathway metabolites were associated with increased symptoms, regardless of T2-status. These pathways are not affected by CS exposure. Further research is needed to define the role of eicosanoids in T2-low severe asthma using interventions to perturb these pathways.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".