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Abstract: Background: Esophageal dysmotility may predispose to Barrett's esophagus (BE). We hypothesized that high‐resolution manometry (HRM) performed with additional physiologic challenge would better delineate dysmotility in BE. Methods: Included patients had typical reflux symptoms and underwent endoscopy, HRM with single water swallows and adjunctive testing with solids and rapid drink challenge (RDC) before ambulatory pH‐impedance monitoring. BE and endoscopy‐negative reflux disease (ENRD) subjects were compared against functional heartburn patient‐controls (FHC). Primary outcome was incidence of HRM contractile abnormalities with standard and adjunctive swallows. Secondary outcomes included clearance measures and symptom association on pH‐impedance. Key Results: Seventy‐eight patients (BE 25, ENRD 27, FHC 26) were included. Water swallow contractility was reduced in both BE (median DCI 87 mm Hg/cm/s) and ENRD (442 mm Hg/cm/s) compared to FHC (602 mm Hg/cm/s; P < .001 and .04, respectively). With the challenge of solid swallows and RDC, these parameters improved in ENRD (solids = 1732 mm Hg/cm/s), becoming similar to FHC (1242 mm Hg/cm/s; P = .93), whereas abnormalities persisted in BE (818 mm Hg/cm/s; P < .01 c.f. FHC). In BE and ENRD, reflux events (67 vs 57 events/24 hour) and symptom frequency were similar; yet symptom correlation was significantly better in ENRD compared to BE, which was comparable to FHC (symptom index 30% vs 4% vs 0%, respectively). Furthermore, bolus clearance and exposure times were more pronounced in BE (P < .01). Conclusions & Inferences: Reduced contractile effectiveness persisted in BE with the more representative esophageal challenge of swallowing solids and free drinking; while in ENRD and FHC peristalsis usually improved, demonstrating peristaltic reserve. Furthermore, symptom association and refluxate clearance were reduced in BE. These factors may underlie BE pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Advances in clinical measurement of esophageal motility and function have improved the assessment of swallowing disorders and reflux symptoms. Variation in data acquisition, analysis, and reporting exists and impacts on diagnosis and management. Aims and Methods: This study examined variation in esophageal manometry methodology between institutions to establish the status in current practice. A structured survey was distributed through international NGM societies using an Internet‐based platform. Questions explored infrastructure, technology, analysis, and reporting. Key Results: Responses were received from 91 centers from 29 countries. Eighteen (20%) centers used “conventional” manometry, 75 (82%) high‐resolution manometry, and 53 (58%) HR impedance manometry. All centers documented motility for single water swallows. The Chicago Classification was applied by 65 (71.4%) centers. In contrast, analysis of EGJ morphology varied widely. Adjunctive testing was often applied: multiple rapid swallows (77%), rapid drink challenge (77%), single solid swallows (63%), and a standard test meal (18%). Of 86 (94.5%) units that offered pH impedance (pH‐Z) studies, approximately half (53.5%) performed tests on acid‐suppressant medication in patients with a high pretest probability (eg, erosive esophagitis). Most (75.6%) centers manually reviewed every reflux event. Others examined pH‐Z data only prior to symptoms. To assess symptom association with reflux events, 73.6% centers analyzed each symptom separately, whereas 29.7% centers pooled symptoms. Conclusions and Inferences: There is marked variation in the data acquisition, analysis, and reporting of esophageal manometry studies. Further efforts to improve quality and uniformity in testing and reporting are required. This survey provides information upon which best‐practice guidelines can be developed. [ABSTRACT FROM AUTHOR]

Background/Aims The Chicago Classification for diagnosis of esophageal motility disorders by high-resolution manometry ( HRM) is based on single water swallows ( SWS). Emerging data suggest that a 'Rapid Drink Challenge' ( RDC) increases sensitivity for motility disorders. This study establishes normal values and diagnostic thresholds for RDC in clinical practice. Methods Two cohort studies were performed in patients with dysphagia or reflux symptoms (development and validation sets). Healthy subjects and patient controls provided reference values. Ten SWS and two 200-mL RDC were performed. Primary diagnosis for SWS was established by the Chicago Classification. Abnormal RDC was defined by impaired esophagogastric junction ( EGJ) function (elevated integrated relaxation pressure during RDC [ IRP- RDC]); incomplete inhibition of contractility during and ineffective contraction after RDC. Diagnostic thresholds identified in the development set were prospectively tested in the validation set. Results Normal values were determined in healthy (n=95; age 37.8 ± 12) and patient controls (n=44; age 46.4 ± 15). Development and validation sets included 178 (54 ± 17 years) and 226 (53 ± 16 years) patients, respectively. Integrated relaxation pressure during RDC was higher for SWS than RDC in all groups (overall P<.001), except achalasia. Rapid Drink Challenge suppressed contractility, except in achalasia type III, spasm, and hypercontractile motility disorders ( P<.001). An effective after-contraction was present more often in health than disease ( P<.001). Optimal diagnostic thresholds identified in the development set ( IRP- RDC ≥12 mmHg achalasia, IRP- RDC ≥ 8mmHg 'all cause' EGJ dysfunction), were confirmed in the validation set (both, sensitivity ~85%, specificity >95%). Conclusions Rapid Drink Challenge contributes clinically relevant information to routine HRM studies, especially in patients with EGJ dysfunction. [ABSTRACT FROM AUTHOR]

Background In the absence of major dysmotility, esophageal manometry with water swallows rarely explains the causes of esophageal symptoms and disease. This methodology development study assessed esophageal function and symptoms during a test meal in patients with reflux symptoms and asymptomatic controls. The impact of this approach on manometric diagnosis and clinical outcome was reviewed. Methods 18 patients with reflux symptoms and 10 healthy volunteers underwent high resolution manometry (HRM) with 5 mL water swallows, 200 mL water drink, and standardized solid test meal followed by 10 min postprandial observation. The number of symptoms associated with esophageal dysfunction ( SAD) divided by total symptoms (dysfunction symptom index [D-SI]) was calculated. Ambulatory reflux pH-monitoring was performed. Final diagnosis and clinical outcome were documented at 2 years. Key Results Meal intake took longer in patients than controls (552 vs 339 s) and this was associated with a higher number of ineffective swallows in this group (51% vs 28%; p < 0.001). No swallowing problems occurred with water swallows but 12/18 (66%) patients had SAD during either the meal or postprandial observations with D- SI >50% in 9/12 (75%). Compared with water swallows, manometric classification was altered in 12/18 (67%) and clinical diagnosis was altered in 7/18 (39%) patients due to test meal observations. Conclusions & Inferences A novel methodology for the detection of symptomatic dysmotility during a test meal and postprandial observation is presented. This technique increased the diagnostic yield of esophageal dysfunction in patients presenting with reflux symptoms. Long-term follow-up indicated that these observations can guide effective clinical management. [ABSTRACT FROM AUTHOR]

Background Measurement of esophago-gastric junction ( EGJ) cross-sectional area ( CSA) and distensibility by an Endolumenal Functional Lumen Imaging Probe (Endo FLIP®) may distinguish between gastro-esophageal reflux disease ( GERD) patients and healthy volunteers ( HV). We aimed to assess the agreement of Endo FLIP® measurements with clinical and physiologic diagnosis of GERD. Methods Twenty-one HV and 18 patients with typical GERD symptoms were studied. After gastroscopy, EGJ CSA, and distensibility were measured by Endo FLIP®. Forty-eight hour esophageal pH monitoring was then performed by a wireless system. The ability of Endo FLIP® to discriminate GERD patient and HVs was assessed. Planned secondary analysis then assessed whether EGJ CSA and distensibility were increased in individuals with pathologic acid exposure. Key Results Healthy volunteers were younger and had lower body mass index ( BMI; both p < 0.001). Pathologic acid exposure was present in 3/21 (14%) HVs and 9/18 (50%) patients ( p = 0.126). At 30 mL Endo FLIP® bag volume, EGJ CSA was higher ( p = 0.058) and EGJ distensibility was lower ( p = 0.020) in HVs than patients. Secondary analysis showed that EGJ measurements were similar in participants with and without pathologic acid exposure ( CSA 98 mm2 vs 107 mm2; p = 0.789, distensibility; p = 0.704). An inverse association between BMI and CSA ( R2 = 0.2758, p = 0.001) and distensibility ( R2 = 0.2005, p = 0.005) was present. Conclusions & Inferences Endolumenal Functional Lumen Imaging Probe is not useful for GERD diagnosis because EGJ CSA and distensibility do not distinguish between HVs and GERD patients defined by clinical presentation or pH measurement. This unexpected result may be due to an important, confounding interaction of obesity. [ABSTRACT FROM AUTHOR]

Background Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. Aims To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. Methods Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. Results MRI visualized a 'mass' of GA form at the oesophago-gastric junction ( OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. Conclusions Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome. [ABSTRACT FROM AUTHOR]

Background Obese patients have an increased risk of gastro-oesophageal reflux disease; however, the mechanism underlying this association is uncertain. Aim To test the hypothesis that mechanical effects of obesity on oesophageal function increase acid exposure and symptoms. Methods Height, weight and waist circumference ( WC) were measured in patients with typical reflux symptoms referred for manometry and 24 h ambulatory pH studies. Symptom severity was assessed by questionnaire. The association between obesity [ WC, body mass index (BMI)], oesophageal function, acid exposure and reflux symptoms was assessed. Results Physiological measurements were obtained from 582 patients (median age 48, 56% female) of whom 406 (70%) completed symptom questionnaires. The prevalence of general obesity was greater in women ( BMI ≥ 30 kg/m2; F 23%:M 16%; P = 0.056), however more men had abdominal obesity ( WC ≥ 99 cm (M 41%:F 28%; P = 0.001)). Oesophageal acid exposure increased with obesity ( WC: R = 0.284, P < 0.001) and was associated also with lower oesophageal sphincter ( LOS) pressure, reduced abdominal LOS length and peristaltic dysfunction (all P < 0.001). Univariable regression showed a negative association of WC with both LOS pressure and abdominal LOS length ( R = −0.221 and −0.209 respectively; both P < 0.001). However, multivariable analysis demonstrated that the effects of increasing WC on oesophageal function do not explain increased acid reflux in obese patients. Instead, independent effects of obesity and oesophageal dysfunction on acid exposure were present. Reflux symptoms increased with acid exposure ( R = 0.300; P < 0.001) and this association explained increased symptom severity in obese patients. Conclusions Abdominal obesity ( waist circumference) is associated with oesophageal dysfunction, increased acid exposure and reflux symptoms; however, this analysis does not support the mechanical hypothesis that the effects of obesity on oesophageal function are the cause of increased acid exposure in obese patients. [ABSTRACT FROM AUTHOR]

Background Symptom based diagnosis is not reliable in patients with swallowing problems, heartburn, and other dyspeptic complaints. The aim of investigation is to provide clinically relevant measurements of gastrointestinal structure and function that explain the cause of symptoms, identify pathology, and guide effective management. Current practice rarely meets these ideals. Purpose This review considers recent advances in technology such as high-resolution manometry (HRM) with esophageal pressure topography (EPT), HRM with impedance, high frequency ultrasound, and endoscopic functional luminal impedance planimetry (Endo-FLIP) that provide new opportunities to identify the pathophysiologic basis of esophageal symptoms and disease. As experience with these new devices increases researchers are developing new methodologies that maximize their utility in clinical practice. For example, application of HRM to assess motility and function during and after a test meal can identify the causes of swallowing problems, reflux and other postprandial symptoms and intra-operative application of Endo-FLIP may help surgeons perform antireflux surgery. These examples illustrate the potential of physiologic measurement to direct rational and effective clinical management for individual patients. [ABSTRACT FROM AUTHOR]

Non-specific esophageal dysmotility with impaired clearance is often present in patients with gastro-esophageal reflux disease (GERD), especially those with erosive disease; however the physio-mechanic basis of esophageal dysfunction is not well defined. Retrospective assessment of patients with erosive reflux disease (ERD; n = 20) and endoscopy negative reflux disease (ENRD; n = 20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n = 20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3 cm break in 30 mmHg isocontour). Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P < 0.023 vs controls, P = 0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18% vs 33%, P = 0.082) and ENRD (22% vs 54%, P = 0.046) but not ERD (62% vs 76%, P = 0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P < 0.017 vs controls and P < 0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r = 0.52 vs 0.27). Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate. [ABSTRACT FROM AUTHOR]

High-resolution manometry (HRM) with spatiotemporal representation of pressure data is a recent advance in esophageal measurement. At present, normal values are available for 5 mL water swallows in the supine position. This study provides reference values for liquid and solid bolus swallows in the upright seated and supine positions. A total of 23 asymptomatic volunteers (11M : 12F, age 20-56) underwent HRM (Manoscan 360; Sierra Scientific Instruments) with 5 mL water and 1 cm bread swallows in the upright and supine positions. Normal values for primary parameters associated with effective bolus transport [proximal transition zone length (PTZ, assesses peristaltic coordination], contraction front velocity (CFV), distal contractile index (DCI) and integrated relaxation pressure (IRP)] are presented. For each parameter, median values along with the 5-95th percentile range are reported. Inter-observer agreement between independent observers is reported using the intra-class correlation coefficient. A higher proportion of swallows were peristaltic for liquids than solids in both the upright and supine positions (both P < 0.05). As workload increases with solid bolus and on moving from the upright to the supine position the esophageal contractile response resulted in a shorter PTZ, a slower CFV, and a more vigorous DCI. Also IRP increased during solid bolus transit (all P < 0.01). There was significant agreement between independent observers for HRM parameters. Normative values for esophageal function for solids as well as liquids and in the 'physiologic', upright position will optimize the utility of HRM studies. The high level of inter-observer agreement indicates that these can be applied as reference values in clinical practice. [ABSTRACT FROM AUTHOR]

Catheter-based esophageal pH-monitoring is used to evaluate patients with suspected gastro-esophageal reflux disease (GERD); however false-negative results may occur due to poor tolerance of the catheter with reduced oral intake and activity, or high day-to-day variation in reflux and symptom events. We assessed diagnostic yield and clinical impact of prolonged, wireless pH-monitoring in patients with negative results from 24-h catheter-based studies and ongoing symptoms. Esophageal acid exposure (percentage time pH <4), Symptom Index, and Symptom Association Probability (SAP) were calculated. Diagnostic yield was assessed using Average (mean) and Worst Day (24-h period with highest acid exposure or symptom load) analyses. Outcome data were assessed 6-36 months (median 24) after initiation of definitive therapy based on physiologic testing. Data from prolonged pH-monitoring up to 96-h (median 72-h) were available from 38 patients. Using Average and Worst Day analysis, esophageal acid exposure was pathologic in 37% and 47%, whereas SAP was positive in 34% and 63% of patients, respectively. Overall using Average and Worst Day analyses, 61% and 76% patients were diagnosed with GERD based on either pathologic acid exposure or positive symptom association. Of 12 patients that underwent antireflux surgery, 10(83%) reported a good outcome at a median 24 months follow-up. Prolonged, wireless pH-monitoring increases test sensitivity and diagnostic yield in patients with continuing esophageal symptoms despite negative 24-h catheter-based pH-studies. Without a definitive diagnosis, many would not have received effective treatment. [ABSTRACT FROM AUTHOR]

Background Standard pH monitoring is performed over 24 h with a naso-oesophageal catheter (C-pH). Limitations include naso-pharyngeal discomfort, nausea and social embarrassment resulting in reduced reflux-provoking activities. Recently a catheter-free pH-monitoring technique has become available. The tolerability and diagnostic yield of this system in patients who failed standard monitoring remain unknown. Aim To examine the tolerability and diagnostic outcome of catheter-free pH-monitoring technique in patients who failed standard monitoring. Methods Patients referred for C-pH and catheter-free pH monitoring completed a tolerability questionnaire. Acid exposure in the distal oesophagus and symptom index (SI) were reviewed. Results Over 4 years, 883/1751 (50%) of patients with typical reflux symptoms referred for C-pH were diagnosed with gastro-oesophageal reflux disease (GERD) based on a pathological percentage time acid exposure (%time pH <4);134 (8%) patients failed C-pH and, of these, 129 successfully completed 2-day catheter-free pH monitoring. Ninety-eight (76%) of these patients had a pathological percentage pH <4 on either day compared with 49/102 (49%) of contemporaneous C-pH patients ( P < 0.01). There was no difference in SI for heartburn (35% vs. 42%; P = 0.49). The questionnaire demonstrated a preference for catheter-free pH monitoring (96%) with less restriction in activities of daily living, naso-pharyngeal discomfort, dysphagia and chest pain. Conclusions Tolerance and satisfaction with catheter-free pH monitoring are high in patients who had previously failed C-pH; catheter-free pH monitoring assists the definitive diagnosis of GERD in this group. [ABSTRACT FROM AUTHOR]

Oesophageal spasm presents with dysphagia and chest pain. Current treatments are limited by poor efficacy and side effects. Studies in health and oesophageal dysmotility show that sildenafil reduces peristaltic pressure and velocity; however the clinical efficacy and tolerability in symptomatic oesophageal spasm remains uncertain. We provided open-label sildenafil treatment to two patients with severe, treatment resistant symptoms associated with oesophageal spasm. The effects of sildenafil on oesophageal function and symptoms were documented by high resolution manometry (HRM). Patients were followed up to assess the efficacy of maintenance treatment with sildenafil b.i.d. HRM revealed focal and diffuse spasm in the smooth muscle oesophagus that were associated with symptoms in both cases, especially on swallowing solids. Lower oesophageal sphincter function was normal. A therapeutic trial of 25–50 mg sildenafil suppressed oesophageal contraction almost completely for water swallows; however effective, coordinated peristalsis returned with reduced frequency of spasm for solid swallows. Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment with 25–50 mg sildenafil b.i.d. without troublesome side effects. This report shows that sildenafil can improve oesophageal function and relieve dysphagia and chest pain in patients with oesophageal spasm in whom other treatments have failed. [ABSTRACT FROM AUTHOR]

Background Cigarette smoking is significantly associated with premature death related and not related to cardiovascular disease (CVD). Whether risk associated with smoking is similar across CVD subtypes and how this translates into years of life lost is not known. Methods and Results We pooled and harmonized individual-level data from 9 population-based cohorts in the United States. All participants were free of clinical CVD at baseline with available data on current smoking status, covariates, and CVD outcomes. We examined the association between smoking status and total CVD and CVD subtypes, including fatal and nonfatal coronary heart disease, stroke, congestive heart failure, and other CVD deaths. We performed (1) modified Kaplan-Meier analysis to estimate long-term risks, (2) adjusted competing Cox models to estimate joint cumulative risks for CVD or noncardiovascular death, and (3) Irwin's restricted mean to estimate years lived free from and with CVD. Of 106 165 adults, 50.4% were women. Overall long-term risks for CVD events were 46.0% (95% CI, 44.7-47.3) and 34.7% (95% CI, 33.3-36.0) in middle-aged men and women, respectively. In middle-aged men who reported smoking compared with those who did not smoke, competing hazard ratios (HRs) were higher for the first presentation being a fatal CVD event (HR, 1.79 [95% CI, 1.68-1.92]), with a similar pattern among women (HR,1.82 [95% CI, 1.68-1.98]). Smoking was associated with earlier CVD onset by 5.1 and 3.8 years in men and women. Similar patterns were observed in younger and older adults. Conclusions Current smoking was associated with a fatal event as the first manifestation of clinical CVD.

Background: Although nighttime reflux symptoms are common, the presence of nocturnal reflux is seldom confirmed with a standard 24 hours pH study., Aim: To study patients with supine nighttime reflux symptoms using prolonged wireless pH monitoring., Methods: In this retrospective study, patients with typical acid reflux symptoms were studied using 96-h pH monitoring. Patients with nighttime reflux symptoms were compared to those without. Night-to-night variability and diagnostic accuracy of 24-, 48- and 72-hours pH studies compared to the 96-hours "gold standard" were evaluated., Results: Of the 105 included patients (61.9% females; mean age 46.8 ± 14.4 years), 86 (81.9%) reported nighttime reflux symptoms, of which 67.4% had pathological supine nocturnal acid exposure in at least one night. There was high variance in night-to-night acid exposure (94% [IQR0-144]), which was larger than the variance in upright acid exposure (58% [IQR32-88]; P < 0.001). When analysing the first 24 hours of the pH study, 32% of patients were diagnosed with pathological supine nighttime acid exposure versus 51% of patients based upon the 96-hours pH-test. The diagnostic accuracy and yield improved with study duration (P < 0.001). Reflux episodes with a lower nadir pH or longer acid clearance time were more prone to provoke nightly symptoms., Conclusions: The majority of patients with nocturnal reflux symptoms had pathological acid exposure in at least one night of the prolonged pH recording. A high night-to-night variability in acid exposure reduces the clinical value and diagnostic yield of pH monitoring limited to 24 hours. Prolonged testing is a more appropriate diagnostic tool for patients with nocturnal reflux symptoms., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)