P11 The Role Of Gabab Receptor Mechanisms In The Human Cough Reflex

Badri, Huda; Gibbard, Carmen; Valdramidou, Dimitra; Canning, BJ; Houghton, Lisa A; Holt, Alison; Wilkinson, Gary; Smith, JA

doi:10.1136/thoraxjnl-2014-206260.161

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“…The effects of lesogaberan on capsaicin evoked coughs differed from our previous observations in healthy volunteers (36). In RCC patients lesogaberan significantly reduced capsaicin evoked cough suggesting an inhibition of the cough reflex, whereas there was no effect in healthy controls.…”

Section: Discussioncontrasting

confidence: 95%

A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough

et al. 2022

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ObjectiveBaclofen is a centrally acting Gamma-aminobutyric acid type B (GABAB) 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 GABAB agonist but its effects on refractory chronic cough are unknown.DesignWe 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 (MR) twice daily (BD) or matched placebo for 2 weeks and then crossed over to the alternative therapy after a 2-week washout. The primary endpoint was 24-hour cough frequency measured with an acoustic monitoring system. Cough responses to capsaicin were also measured and gastro-oesophageal reflux assessed by 24 h pH/impedance at screening.ResultsTwenty-two patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan [female (73%), mean age 63.7 ±s.d.7.2 years, median cough duration 10.5 years (IQR 5.8–17.0), mean 45 (95%CI 29–67) reflux events in 24hrs and 2 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.ConclusionsLesogaberan improved cough hyper-sensitivity and the number of bouts of coughing but not coughs per hour. This implies a possible role for peripheral GABAB receptors in refractory chronic cough.

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Section: Discussioncontrasting

confidence: 95%