期刊
ERJ OPEN RESEARCH
卷 8, 期 1, 页码 -出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/23120541.00546-2021
关键词
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资金
- MRC
- AstraZeneca [MR/K015141/1]
- NIHR Manchester Biomedical Research Centre
- Dept of Medicine, McMaster University
- North West Lung Centre Pickering Fellowship
- Wellcome Investigator in Science Award
The study found that lesogaberan may help alleviate refractory chronic cough by improving cough responses to capsaicin and the number of cough bouts.
Objective Baclofen is a centrally acting gamma-aminobutyric acid type B (GABA(B)) receptor agonist which reduces gastro-oesophageal reflux and suppresses the cough reflex; however, central nervous system side-effects limit its use. Lesogaberan is a novel peripherally acting GABA(B) agonist, but its effects on refractory chronic cough are unknown. Design We performed a single-centre, placebo-controlled, double-blind randomised crossover study in patients with chronic cough, refractory to the treatment of underlying conditions. Patients were randomised to treatment with lesogaberan 120 mg modified release twice daily or matched placebo for 2 weeks and then crossed over to the alternative therapy after a 2-week washout. The primary end-point was 24-h cough frequency measured with an acoustic monitoring system. In addition, cough responses to capsaicin were measured, and gastro-oesophageal reflux assessed by 24-h pH/impedance at screening. Results 22 patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan (female (73%); mean +/- SD age 63.7 +/- 7.2 years; median (interquartile range) cough duration 10.5 (5.8-17.0) years; mean (95% CI) 45 (29-67) reflux events in 24 h; two patients had abnormal oesophageal acid exposure times). Although lesogaberan reduced cough counts by 26% over placebo, this did not reach statistical significance (p=0.12). However, lesogaberan did significantly improve cough responses to capsaicin (p=0.04) and the number of cough bouts (p=0.04) compared with placebo. Lesogaberan was well tolerated in this study. Conclusions Lesogaberan improved cough hypersensitivity and the number of bouts of coughing, but not coughs per hour. This implies a possible role for peripheral GABA(B) receptors in refractory chronic cough.
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