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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Background Hydrogen and methane breath tests (HMBT) are widely used clinical investigations but lack standardization. To address this, the North American Consensus (NAC) group published evidence-based recommendations for HMBT. Aims To evaluate results obtained using NAC recommendations for HMBT, compared to retrospective data that utilized guidelines previously recommended. Methods HMBT data from 725 patients referred for small intestinal bacterial overgrowth (SIBO) and/or carbohydrate malabsorption (CM) testing were analyzed. Data were compared regarding dose of substrate for SIBO testing (16 vs. 10 g lactulose, and 50 vs. 75 g glucose) and the effect of post-ingestion sampling period for malabsorption testing. The effect of different recommended cut-off values for SIBO were examined. Results Substrate dose did not affect methane production. 10 g lactulose significantly reduced positive SIBO results compared to 16 g lactulose (42 vs. 53%, p = 0.04). 75 g glucose significantly increased positive results compared to 50 g glucose (36 vs. 22%, p = 0.04). Provoked symptoms were significantly more prevalent in patients testing positive by both North American Consensus and Ledochowski cut-off values. 34.5% of patients tested positive for CM at 180-min compared to 28% at 120-min (not significant, p = 0.19). Conclusions and Inferences 10 g lactulose substrate produces fewer positive SIBO results than 16 g lactulose, while 75 g glucose dose produces more positive SIBO results than 50 g. Performing CM breath tests for 180 min increases number of positive results when compared to 120 min. SIBO cut-off timings require further investigation, but our findings broadly support the NAC recommendations for SIBO and CM testing.

Introduction Short bowel syndrome (SBS) is a leading cause of intestinal failure (IF) and the need for long term home parenteral nutrition (HPN). Understanding the anatomical features and nutritional requirements of this sub set of patients within