Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high‐resolution manometry (HRM). Fifty‐two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two‐years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion.

Background Mean nocturnal baseline impedance (MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden. Aim To assess the predictive value of MNBI on symptomatic outcomes after antireflux therapy. Methods In this prospective observational cohort study, pH-impedance studies performed over a 5-year period were reviewed. Baseline impedance was extracted from 6 channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal esophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7, and 9 cm, and 15 and 17 cm, respectively. Symptomatic outcomes were measured as changes in global symptom severity (GSS, rated on 100-mm visual analog scales) on prospective follow-up after medical or surgical antireflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes. Results Of 266 patients, 135 (50.8%) were tested off PPI therapy and formed the study cohort (52.1±1.1 yrs, 63.7% F). The 59 with elevated acid exposure time (AET) had lower composite and distal MNBI values than those with physiologic AET (p<0.0001), but similar proximal MNBI (p=0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r=−0.5, p<0.001), but not proximal MNBI (Pearson's r=0, p=0.72). After prospective follow-up (94 patients followed for 3.1±0.2 yrs), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement. Conclusions Distal esophageal MNBI negatively correlates with AET and, when assessed off PPI therapy, is independently predictive of symptomatic improvement following antireflux therapy.

Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.

OBJECTIVES pH-impedance testing detects reflux events irrespective of pH, but its value in predicting treatment outcome is unclear. We prospectively evaluated subjects treated medically after pH-impedance testing to determine predictors of symptom improvement. METHODS Subjects referred for pH-impedance testing completed questionnaires in which dominant symptoms and global symptom severity (GSS) were recorded. Acid-reflux parameters (acid-exposure time, AET; symptom association by Ghillebert probability estimate, GPE; symptom index, SI) and impedance reflux parameters (reflux-exposure time, RET; number of reflux events; GPE and SI with impedance data) were extracted. Symptoms and GSS were prospectively reevaluated after medical therapy. Univariate and multivariate analyses determined predictors of GSS improvement following medical management. RESULTS Over 5 years, 128 subjects (mean 53.3 ± 1.3 years, 66.4% female; typical symptoms 57.0%, 53.9% tested on therapy) underwent pH-impedance testing and subsequent medical therapy for reflux symptoms, and completed required questionnaires. On follow-up 3.35 ± 0.14 years later, mean GSS declined by 45.0%, with 42.2% patients reporting ≥50% GSS improvement. On univariate analysis, total AET, AET ≥4.0%, and GPE for all reflux events predicted both linear and ≥50% GSS improvement, but RET and number of reflux events did not. On multivariate analysis, controlling for testing on or off therapy, only AET (P = 0.003) and GPE for all reflux events (P = 0.029) predicted GSS improvement. CONCLUSIONS Acid-based reflux parameters offer greater value over impedance-based nonacid-reflux parameters in predicting symptomatic responses to proton pump inhibitor (PPI) therapy. Our findings support conducting pH-impedance studies off PPI therapy to maximize clinical utility in predicting outcome.