Methanogens, Methane and Gastrointestinal Motility

Anaerobic fermentation of the undigested polysaccharide fraction of carbohydrates produces hydrogen in the intestine which is the substrate for methane production by intestinal methanogens. Hydrogen and methane are excreted in the flatus and in breath giving the opportunity to indirectly measure their production using breath testing. Although methane is detected in 30%-50% of the healthy adult population worldwide, its production has been epidemiologically and clinically associated with constipation related diseases, like constipation predominant irritable bowel syndrome and chronic constipation. While a causative relation is not proven yet, there is strong evidence from animal studies that methane delays intestinal transit, possibly acting as a neuromuscular transmitter. This evidence is further supported by the universal finding that methane production (measured by breath test) is associated with delayed transit time in clinical studies. There is also preliminary evidence that antibiotic reduction of methanogens (as evidenced by reduced methane production) predicts the clinical response in terms of symptomatic improvement in patients with constipation predominant irritable bowel syndrome. However, we have not identified yet the mechanism of action of methane on intestinal motility, and since methane production does not account for all constipation associated cases, there is need for high quality clinical trials to examine methane as a biomarker for the diagnosis or as a biomarker that predicts antibiotic treatment response in patients with constipation related disorders.

Bravo 48-hour Wireless pH Monitoring in Patients With Non-cardiac Chest Pain. Objective Gastroesophageal Reflux Disease Parameters Predict the Responses to Proton Pump Inhibitors

BACKGROUND/AIMS: In patients with non-cardiac chest pain (NCCP), gastroesophageal reflux disease (GERD) is the commonest cause and ambulatory pH is of great value in identifying these patients. However, parameters in the context of predicting therapeutic response are still unknown. By extending the monitoring period, we could better evaluate the best evidence for GERD association. Our aims were (1) to compare the outcomes of 48-hour pH monitoring to 24-hour and (2) to determine whether objective parameters could predict the treatment success in patients with NCCP using Bravo pH system. METHODS: Pathological esophageal acid reflux (PEAR) and positive symptom index (SI) were calculated after 24-hour and compared to the 48-hour study. Evidence suggestive of GERD diagnosis was considered if PEAR and/or SI (+) were present on each different day. After pH study, all patients received proton pump inhibitor twice a day for 4 weeks. Treatment success was determined at the end of therapy. RESULTS: Thirty-two patients with NCCP participated. GERD was identified in 20 (62.5%) patients; 17 (53.1%) had PEAR, 3 (9.4%) SI (+) and 7 (22%) both. Twelve (41%) patients exhibited PEAR values on day 1, while 17 after 2 days; a 12.1% gain. SI (+) was found in 6 patients (18.8%) on day 1 and in 4 more on day 2, a gain of 12.5%. Significantly higher proportion of patients with GERD indicators showed improvement compared to those without (90% vs 16.7%, P < 0.005). CONCLUSIONS: In patients with NCCP, 48-hour pH measurement identified GERD as the cause of NCCP with an increased yield by almost 12% compared to 12 hours. Objective GERD parameters could predict response to antireflux therapy.

Yield of Combined Impedance-pH Monitoring for Refractory Reflux Symptoms in Clinical Practice

BACKGROUND/AIMS: In patients with gastroesophageal reflux disease, persistent symptoms on proton pump inhibitor (PPI) therapy may be due to residual acid or non-acid reflux. Combined impedance-pH has been suggested to be superior to pH alone in the management of refractory patients to PPI. The utility of implementation of this technique in every day clinical practice is still unknown. The aim of this study was to investigate the outcomes of patients studied with combined impedance-pH and to evaluate the yield of additional impedance monitoring over pH alone in patients with persistent gastroesophageal reflux disease symptoms. METHODS: Seventy-one patients (31 men; mean age, 49.1 +/- 15.5 years) on PPI therapy underwent combined impedance-pH for persistent typical (76%) or atypical (49%) symptoms. RESULTS: During impedance-pH study, 44 (62%) patients reported symptoms. A positive symptom index (SI) was found in 21 (48%) patients: 8 (18.2%) had a positive SI for acid reflux, 9 (20.5%) for non-acid reflux and 4 (9.1%) for mixed reflux. Addition of impedance allowed association between reflux and symptoms in 20.5% of patients who would have been missed by pH study alone. Heartburn was the most prevalent symptom associated with acid reflux, whereas regurgitation and ear, nose and throat symptoms were associated with non-acid reflux. CONCLUSIONS: The use of combined impedance-pH monitoring substantially increased the diagnostic yield compared to pH alone. With SI analysis, 20.5% of patients received a diagnosis that could not have been achieved with pH testing alone.