Mepolizumab for the treatment of refractory chronic cough in patients with eosinophilic airways disease (MUCOSA): a randomised, double-blind, parallel-group, placebo-controlled trial
Bibliographic record
Abstract
Objective Patients presenting with chronic cough often have eosinophilic airways disease that remains refractory despite inhaled or oral corticosteroids. Studies in asthma patients have shown that eosinophils co-localise with airway sensory nerves, and after allergen challenge, are associated with neuronal sensitivity. We evaluated whether mepolizumab, a monoclonal antibody targeting interleukin-5, reduces cough in patients with eosinophilic airways disease. Methods We conducted a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial of 30 patients with refractory chronic cough and eosinophilic airways disease (sputum eosinophils ≥2%). Patients underwent 1:1 randomisation to receive subcutaneous mepolizumab (100 mg) or placebo every 4 weeks for 12 weeks. Change from baseline in 24-h cough frequency at 14 weeks represented the primary end-point. Measurements and main results Compared to placebo, mepolizumab did not lead to improvements in 24-h cough frequency at 14 weeks (percentage change relative to placebo +18.0%, 95% CI −46.4–160.1%; p=0.99). We found no between-group differences in awake cough frequency, sleep cough frequency, cough severity on the 100-mm visual analogue scale, and quality of life on the Leicester Cough Questionnaire. Mepolizumab significantly reduced blood eosinophils compared to placebo at week 14 (mean difference −237.7 cells·µL −1 , 95% CI −328.3–−147.1 cells·µL −1 ; p<0.0001) and had a significant overall effect in reducing sputum eosinophils over the study (p=0.045). No major adverse events occurred. Conclusion In patients with refractory chronic cough and persistent eosinophilia despite inhaled corticosteroid therapy, mepolizumab did not improve cough despite reducing blood and sputum eosinophils. Targeting eosinophils might not impact cough in these patients, and their cough is probably driven by alternative mechanisms.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".