Mepolizumab for the treatment of refractory chronic cough in patients with eosinophilic airways disease (MUCOSA): a randomised, double-blind, parallel-group, placebo-controlled trial.

Studies in asthma patients have shown that eosinophils co-localise with airway sensory nerves, and after allergen challenge, are associated with neuronal sensitivity.

在哮喘患者的研究中发现，嗜酸性粒细胞与气道感觉神经共定位，在过敏原挑战后，它们与神经敏感性相关。

We evaluated whether mepolizumab, a monoclonal antibody targeting interleukin-5, reduces cough in patients with eosinophilic airways disease.

我们评估了靶向白细胞介素-5的单克隆抗体mepolizumab是否能减少嗜酸性粒细胞气道疾病患者的咳嗽症状。

Methods

We conducted a single-centre, randomised, double-blind, parallel-group, placebo-controlledtrial of 30 patients with refractory chronic cough and eosinophilic airways disease (sputum eosinophils ≥2%).

我们进行了一项针对30名难治性慢性咳嗽和嗜酸性粒细胞气道疾病的患者（痰液嗜酸性粒细胞≥2%）的单中心、随机、双盲、平行组、安慰剂对照试验。

Patients underwent 1:1 randomisation to receive subcutaneous mepolizumab (100 mg) or placebo every 4 weeks for 12 weeks.

患者按1:1的比例随机接受皮下注射mepolizumab（100 mg）或安慰剂，每4周一次，持续12周。

Change from baseline in 24-h cough frequency at 14 weeks represented the primary end-point.

14周时24小时咳嗽频率从基线的变化代表主要终点。

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).

与安慰剂相比，14周时mepolizumab并未导致24小时咳嗽频率的改善（相对于安慰剂的百分比变化为+18.0%，95%置信区间为-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.

我们在清醒时咳嗽频率、睡眠时咳嗽频率、使用100毫米视觉模拟量表评估的咳嗽严重程度以及使用莱斯特咳嗽问卷评估的生活质量方面，未发现组间差异。

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).

Mepolizumab 在第14周与安慰剂相比显著降低了血液嗜酸性粒细胞数量，平均差异为 -237.7 cells·µL-1，95% 置信区间为 -328.3--147.1 cells·µL-1；p<0.0001，并在整个研究期间显著减少了痰液中嗜酸性粒细胞的数量（p=0.045）。

No major adverse events occurred.

未发生重大不良事件。

Conclusions

In patients with refractory chronic cough and persistent eosinophilia despite inhaled corticosteroid therapy, mepolizumab did not improve cough despite reducing blood and sputum eosinophils.

对于吸入性皮质类固醇治疗无效的难治性慢性咳嗽和持续性嗜酸性粒细胞增多的患者，美泊利单抗并未改善咳嗽症状，尽管它减少了血液和痰液中的嗜酸性粒细胞数量。

Targeting eosinophils might not impact cough in these patients, and their cough is probably driven by alternative mechanisms.

针对嗜酸性粒细胞的治疗可能不会影响这些患者的咳嗽，他们的咳嗽可能是由其他机制所驱动。