Houghton, Lesley A.

SummaryBackgroundAlthough bloating is a highly prevalent and troublesome symptom in irritable bowel syndrome with constipation (IBS‐C), treatment is empirical with no specific guidelines for its management.AimTo conduct a pairwise and network meta‐analysis, using a frequentist approach, of Food and Drug Administration‐licensed drugs for IBS‐C comparing their efficacy for abdominal bloating as a specific endpoint.MethodsWe searched the medical literature through December 2020 to identify randomised controlled trials (RCTs) in IBS‐C, with abdominal bloating reported as a dichotomous assessment. Efficacy of each drug was reported as a pooled relative risk (RR) with 95% confidence intervals (CIs) to summarise effect of each comparison tested. Treatments were ranked according to their P‐score.ResultsWe identified 13 eligible RCTs, containing 10 091 patients. Linaclotide 290 µg o.d., lubiprostone 8 µg b.d., tenapanor 50 mg b.d. and tegaserod 6 mg b.d. were all superior to placebo for abdominal bloating in patients with IBS‐C, in both pairwise and the network meta‐analyses. Linaclotide demonstrated the greatest improvement in abdominal bloating in both pairwise and network meta‐analysis (RR of failure to achieve an improvement in abdominal bloating = 0.78; 95% CI 0.74‐0.83, number needed to treat = 7, P‐score 0.97). Indirect comparison revealed no significant differences between individual drugs.ConclusionsWe found all licensed drugs for IBS‐C to be superior to placebo for abdominal bloating. Linaclotide appeared to be the most efficacious at relieving abdominal bloating. Further research is needed to assess long‐term efficacy of these agents and to better understand the precise mechanism of improving bloating.

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

INTRODUCTION: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux—a prerequisite of aspiration), and pulmonary function in patients with IPF. METHODS: We prospectively recruited 35 patients with IPF (aged 53–75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment. RESULTS: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux ( P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = −0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = −0.478; P = 0.098) and number of proximal events (r = −0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = −0.520; P = 0.039) and inspiratory LESP (r = −0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008). DISCUSSION: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs.

INTRODUCTION: High-resolution manometry using the Chicago Classification is standard in the evaluation of esophageal motility. When the relaxation of the esophagogastric junction is impaired and achalasia excluded, esophagogastric junction outflow obstruction (EGJ-OO) is diagnosed and the esophageal body is essentially ignored. We sought to characterize the function of the esophageal body in consecutive patients with EGJ-OO. METHODS: Retrospective review of the esophageal manometry findings in consecutive patients where there was computer recognition of EGJ-OO collected over a 2-month period. In each case, the esophageal body was reviewed manually and results reported independent of the suggested computer diagnosis. RESULTS: 116 patients underwent manometry over a 2-month period and 30 (26%) were identified as having EGJ-OO. The indications for testing included chronic cough (n = 5), GERD (n = 8), dysphagia (n = 9) and esophageal evaluation associated with severe lung disease or transplantation (n = 8). The mean IRP was 20.8 (range 16-33.6) and did not vary depending on indication ( P = 0.381). Computer interpretation was EGJ-OO in all patients without mention of the esophageal body. After review, 11 (37%) had an additional esophageal diagnosis. In effective esophageal motility (IEM) was the most prevalent among them (IEM-8, achalasia-2, jackhammer esophagus-1; P = 0.020). The frequency of an additional esophageal diagnosis was significantly different between GERD (0%) and dysphagia (66%; P = 0.004), but not between other groups (i.e. 40% in cough and 37.5% in transplant group). An esophageal body diagnosis was significantly more likely in patients with IRP > 25 (80%) compared with those with IRP < 25 (28%; P = 0.028). CONCLUSION: 1-EGJ-OO is common in patients referred for esophageal manometry. 2-An additional esophageal body diagnosis is common in those with EGJ-OO.3-Esophageal diagnoses are more common in patients with dysphagia and in those with a very high IRP. The body of the esophagus is important in cases of EGJ-OO and should be reported independent of the computer-generated interpretation of the Chicago Classification.

Objective Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty. Design We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score. Results We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily. Conclusion In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.

Goals: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD). Background: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure. Study: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance. Results: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723). Conclusion: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient’s post-LTx.

AbstractBackgroundProximal reflux and incomplete transit of boluses swallowed are risk factors for obstructive chronic lung allograft dysfunction (o‐CLAD) post‐lung transplantation (LTx). Likewise, so is esophagogastric junction outflow obstruction (EGJOO), but not hypo‐contractility, when diagnosed using Chicago Classification (CC) v3.0. Given, peristaltic breaks as defined using CCv2.0 can prolong esophageal clearance, both swallowed and refluxed, but which are deemed within normality using CCv3.0, our aim was to determine whether hypo‐contractility as diagnosed using CCv2.0, influences the association with reflux, along with its clearance, and that of boluses swallowed, and thus its association to allograft failure.MethodsEsophageal motility abnormalities were classified using CC v3.0 and v2.0 in 50 patients post‐LTx (26 female, 55 years (20‐73 years)).ResultsReclassification from CCv3.0 to v2.0 resulted in 7 patients with normal motility being reclassified to hypo‐contractility (n = 6) or hyper‐contractility (n = 1); 2 patients with hypo‐contractility to normal motility; and 3 patients with EGJOO without hyper‐contractility to EGJOO with hyper‐contractility. The main consequence of reclassification was that the sub‐group exhibiting hypo‐contractility became more likely to have abnormal numbers of reflux events (P = .025) and incomplete bolus transit (P = .002) than those with normal motility using CCv2.0; associations not seen using CCv3.0. Irrespective of CC used only patients with EGJOO appeared more likely to develop o‐CLAD than those with normal motility (P < .05).ConclusionsIrrespective of CC used, o‐CLAD appears linked to EGJOO. CCv2.0 however, accentuates the increased reflux and incomplete bolus transit associated with hypo‐contractility post‐LTx, suggesting that these motor abnormalities, though considered minor, may be of importance after lung transplant.

Abstract Background Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life‐time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a ‘large’ pool of IBS patients across Europe and even the world however, might help identify sub‐populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi‐centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four‐year dialogue amongst experts associated with the European COST action BM1106 GENIEUR ( www.GENIEUR.eu ).