Esophageal Acid Exposure In Patients Research Articles

RefluxStop – A Novel Device to Address Gastroesophageal Reflux Disease in the Context of Esophageal Hypomotility

Abstract Background RefluxStop is a non-active, implantable medical device intended to reduce esophageal acid exposure in patients with gastroesophageal reflux disease (GERD). RefluxStop does not affect the esophageal lumen and thus might also be suited for patients with esophageal hypomotility. Aims To report short-/midterm functional outcomes after implantation of RefluxStop. Methods All patients who received laparoscopic implantation of the RefluxStop device from 09/2018-12/2022 in a university hospital were included for retrospective analysis. Subjective (GERD-HRQL-questionnaires; after six weeks and every six-month thereof) and objective data (24h-pH-manometry, barium swallows and upper endoscopies) are reported as functional outcome parameters. Results Forty-five patients were included. Median age was 49.3y (min 28.1– max 76.8), median Body Mass Index 28kg/m2 (19-34), and 21 patients were female (46.7%). Nine patients (20%) had esophagitis Los Angeles grade C or more, 3 had non-acidic reflux (7%), and 32 (71%) had esophageal motility disorders. Primary presenting symptoms were typical in 31(69%), pain or dysphagia in 5(11%), respiratory in 8(18%) and nausea in 1 patient (2%). GERD-HRQL score was significantly reduced from baseline to 6 weeks postop (23.9 and 4.3 (p < 0.001)) and to last follow-up (6.8, p = 0.021). In the last follow-up, after a median of 3.2y, primary presenting symptoms were gone in 31(69%), improved in 6(13%), and stayed the same in 2(4%). Typical symptoms were gone or improved in 34 of 37 patients (92%), dysphagia and pain in 12 of 15 patients (80%), and respiratory symptoms in all of 14 patients. De novo bloating occurred in 1 patient and was improved or gone in 5 patients; no diarrhea was seen. Conclusions RefluxStop shows promising results over four years in a challenging patient population burdened with GERD and esophageal motility disorders.

Analysis of clinical features and motility characteristics of ineffective esophageal motility

Objective To clarify the correlation between the clinical characteristics, esophageal motility features and esophageal acid exposure in patients with ineffective esophageal motility (IEM). Methods From January 2016 to March 2018, at Peking University First Hospital, 22 IEM patients diagnosed by esophagus high-resolution manometry (HRM) and 24 individuals with normal HRM results were enrolled. Clinical features, parameters of esophageal HRM and results of esophageal 24-hour pH monitoring of IEM patients and the individuals with normal HRM results were compared. According to the median distal contraction integral (DCI) of ten swallows, the IEM patients were divided into mild-IEM group (DCI 250-450 mmHg·s·cm (1 mmHg=0.133 kPa)) (14 cases) and severe-IEM group (DCI<250 mmHg·s·cm) (eight cases). The clinical features and esophageal motility were compared between normal HRM group, mild-IEM group and severe-IEM group. T test, chi-square test and one-way analysis of various were used for statistical analysis. Results The age of IEM group was older than that of normal HRM group ((64.5±11.2) years vs. (50.3±18.2) years), and the difference was statistically significant (t=-3.135, P=0.003). The lower esophageal sphincter pressure (LESP) of IEM group was lower than that of normal HRM group ((17.0±6.8) mmHg vs. (22.3±7.2) mmHg), and the difference was statistically significant (t=2.516, P=0.016). There were 15 cases in normal HRM group and 14 patients in IEM group who underwent esophageal 24-hour pH monitoring and there were five and two patients with abnormal acid exposure time (AET) in normal HRM group and IEM group, respectively. The length of proximal esophageal body (PEB) pressure zone of severe-IEM group was shorter than those of normal HRM group and mild-IEM group ((2.8±1.5) cm vs.(4.2±0.7) cm and (4.6±0.9) cm), and the differences were statistically significant (t=2.397 and 3.432, P=0.044 and 0.003). The integrated relaxation pressure (IRP) and LESP of normal HRM group were both higher than those of mild-IEM group ((9.3±2.9) mmHg vs. (7.2±3.3) mmHg, (22.3±7.2) mmHg vs. (15.4±7.1) mmHg), and the differences were statistically significant (t=2.148 and 2.843, P=0.038 and 0.007). There were six and eight patients in mild-IEM group and severe-IEM group who underwent esophageal 24-hour pH monitoring, respectively, and two patients in mild-IEM had abnormal AET. Conclusions The LESP of IEM patients is low. The clinical features and AET of IEM patients are not associated with the severity of IEM. In patients with severe IEM, the proximal and distal esophageal contractility is weakened, and the length of PEB pressure zone is shortened. Key words: Esophageal sphincter, upper; Ineffective esophageal motility; High-resolution manometry; Proximal esophageal body

Effect of high-fat, standard, and functional food meals on esophageal and gastric pH in patients with gastroesophageal reflux disease and healthy subjects.

To investigate the effects of different test meals on esophageal and intragastric pH in patients with gastroesophageal reflux disease (GERD) and healthy subjects and to demonstrate the relationship between esophageal acid exposure (EAE) and gastric pH. We enrolled patients with reflux esophagitis (RE; n = 15), nonerosive reflux disease (NERD; n = 12) and healthy subjects (n = 10). Four pH electrodes were used to monitor the pH of the distal esophagus, upper border of the lower esophageal sphincter, gastric fundus, and gastric body for 26 hours. Isocaloric and isovolumetric high-fat, standard, and functional meals were supplied randomly to the participants. The EAE and gastric acidity of each meal in fasting and postprandial states were compared. High-fat meals significantly increased postprandial EAE in patients with RE and NERD. EAE was higher after a high-fat meal than after a standard or functional food meals at the fourth hour postprandially in patients with RE (P < 0.05). Patients with NERD reported fewer symptoms after a functional food meal than after high-fat and standard meals (0 [interquartile range {IQR} 0-1] vs 1 [IQR 0-2] vs 3 [IQR 1-4], P = 0.014). Compared with high-fat and standard meals, functional food meal significantly decreased gastric acidity in patients with RE. EAE was significantly related to gastric acidity in patients with RE. High-fat meals increased EAE in patients with RE and NERD. Functional food could serve as adjuvant therapy in GERD patients. EAE was related to gastric acidity in RE patients.

Use of a Sleep Positioning Device Significantly Reduces Esophageal Acid Exposure in Lung Transplant Recipients: 2017 Presidential Poster Award

Introduction: Despite advancements in surgical techniques and medical management, lung transplantation remains one of the highest risk solid organ transplants. Patients with lung disease and those who undergo transplantation have been found to display a greater prevalence of gastroesophageal reflux disease (GERD). While the exact pathophysiologic mechanism remains unknown, GERD has been established as an independent and modifiable risk factor for the development of transplant rejection. Additional studies have also displayed a benefit of using an incline wedge pillow in patients with GERD. The goal of this study is to evaluate if a sleep-positioning device (SPD) decreases esophageal acid exposure in patients who have undergone lung transplantation. Methods: This is a single center IRB approved restrospective study designed to evaluate the effect of GERD on patients who have undergone lung transplantation. Patients were identified upon referral to a subspecialty-swallowing center, at which point were provided a SPD for persistent symptoms of GERD or had undergone a positive ambulatory esophageal pH study. Their medical records were then evaluated for esophageal pH study results in addition to markers of pulmonary function. Results: A total of twenty-seven patients were provided a SPD, twenty-four of who had previously undergone formal pH testing. Of this cohort, 96% had already been prescribed a proton pump inhibitors which were held for seven days prior to pH testing. Following the initiation of nightly SPD use, nine individuals had repeat pH tests used for comparison. Significant improvements in percentage of total time spent below a pH of four (Pre 12.4% to Post 5.3%; P<0.05) as well as in the supine position (13.6% to 2.9%; P<0.05) were identified. Use of the SPD was associated with 49.7% and 72.9% reductions in percent of time spent with esophageal pH below four in total and supine times respectively. Conclusion: GERD has been well established as a modifiable risk factor for the development of lung allograft failure that manifests as declines in forced expiratory volumes. This analysis has shown significant reductions in esophageal acid exposure following the use of a sleep-positioning device in addition to concurrent anti-secretory therapy. Given the inverse relationship between duration of abnormal esophageal acid exposure and forced expiratory volume, this data suggests the potential role for a SPD in the management of GERD in lung transplant recipients.Figure: Effect of the SPD on total time esophageal pH recorded as less than 4.0.Figure: Effect of the SPD on supine time esophageal pH recorded as less than 4.0.Figure: Birds eye and lateral views of the sleep positioning device provided to lung transplant recipients.

Role of Age, Gender and Race in Pathological Esophageal Acid Exposure in Patients With Noncardiac Chest Pain

Role of Age, Gender and Race in Pathological Esophageal Acid Exposure in Patients With Noncardiac Chest Pain

Association of Thoraco-Abdominal Pressure Gradient and Esophageal Acid Exposure in Patients with End-Stage Lung Disease

Masuda, Takahiro MD; Singhal, Saurabh MBBS; Roy, Sreeja Biswas MBBS; Smith, Michael; Huang, Jasmine L. MD, FACS; Mittal, Sumeet K. MD, FACS; Bremner, Ross M. MD, PhD Author Information

Mechanisms underlying excessive esophageal acid exposure in patients with gastroesophageal reflux disease

The cause of reflux esophagitis (RE) is excessive esophageal acid exposure. Acid reflux and acid clearance after acid reflux are important factors related to excessive esophageal acid exposure. The main mechanism responsible for acid reflux is transient lower esophageal sphincter relaxation (TLESR), which is LES relaxation not associated with swallowing, and acid reflux caused by low LES pressure is rare. The frequency of TLESR in the postprandial period does not significantly differ between healthy subjects and gastroesophageal reflux disease (GERD) patients; however, the proportion of acid reflux episodes during TLESR is significantly higher in GERD patients. The layer of acid that appears above the dietary layer immediately below the esophagogastric junction (acid pocket) is attracting increasing attention as a cause of the difference in the proportion of acid reflux episodes during TLESR. The proportion of acid reflux episodes during TLESR is significantly higher when the acid pocket is present in the hernia sac than when it is located below the diaphragm. The acid pocket also shows upward migration and reaches the esophageal side of the esophagogastric junction, and the acid pocket itself has been suggested to cause mucosal damage in the lower esophagus. The amplitude and success rate of primary peristalsis decreases with increases in the severity of RE, leading to excessive esophageal acid exposure. Furthermore, the success rate of secondary peristalsis is lower in GERD patients than in healthy subjects.

Esophagogastric Junction Morphology and Distal Esophageal Acid Exposure.

The Chicago classification has recently added a morphological subclassification for the esophagogastric junction (EGJ). Our aim was to assess the distal esophageal acid exposure in patients with this new Chicago EGJ-type IIIa and IIIb classification. From a prospectively collected high-resolution manometry (HRM) database, we identified patients who underwent 24-h pH study between October 2011 and June 2015 and were diagnosed with EGJ-type III based on HRM. Chicago EGJ-type III is defined as the inter-peak nadir pressure ≤gastric pressure and a lower esophageal sphincter (LES)-crural diaphragm (CD) separation >2cm [IIIa-pressure inversion point (PIP) remains at CD level and IIIb-PIP remains at LES level]. We classified the patients into reflux group [DeMeester score >14.72 or Fraction time pH (<4)>4.2%] and non-reflux group based on 24-h pH study. Fifty patients were identified that satisfied the study criteria, of which 37 patients (74%) were EGJ-type IIIa. In those with EGJ-type IIIb, abdominal LES length (AL) in reflux group was significantly shorter than the non-reflux group (0.8 vs. 1.8, p<0.05). EGJ-type IIIa patients showed significantly higher value for DeMeester score and Fraction time pH and more often had a positive pH study than EGJ-type IIIb patients (DeMeester score: 26.7 vs. 11.7, p<0.05; Fraction time pH: 7.9 vs. 2.6, p<0.05; positive pH study: 81.1 vs. 30.8%, p<0.001). Reflux was more common in LES-CD≥3cm than that in LES-CD<3cm (85 vs. 56.7%, p<0.05). A subset of patients with >2-cm LES-CD separation (type IIIb) maintain a physiological intra-abdominal location of the EGJ and are less likely to have reflux. A LES-CD≥3cm seems to discern a hiatus hernia of clinical significance.

Effects of omeprazole or anti-reflux surgery on lower oesophageal sphincter characteristics and oesophageal acid exposure over 10 years

Objective: To compare the effect of anti-reflux surgery (ARS) versus proton pump inhibitor therapy on lower oesophageal sphincter (LOS) function and oesophageal acid exposure in patients with chronic gastro-oesophageal reflux disease (GORD) over a decade of follow-up.Material and methods: In this randomised, prospective, multicentre study we compared LOS pressure profiles, as well as oesophageal exposure to acid, at baseline and at 1 and 10 years after randomisation to either open ARS (n = 137) or long-term treatment with omeprazole (OME) 20–60 mg daily (n = 108).Results: Median LOS resting pressure and abdominal length increased significantly and remained elevated in patients operated on with ARS, as opposed to those on OME. The proportion of total time (%) with oesophageal pH <4.0 decreased significantly in both the surgical and medical groups, and was significantly lower after 1 year in patients treated with ARS versus OME. After 10 years, oesophageal acid exposure was normalised in both groups, with no significant differences, and bilirubin exposure was within normal limits. After 10 years, patients with or without Barrett’s oesophagus did not differ in acid reflux control between the two treatment options.Conclusions: Open ARS and OME were both effective in normalising acid reflux into the oesophagus even when studied over a period of 10 years. Anatomically and functionally the LOS was repaired durably by surgery, with increased resting pressure and abdominal length.

Electrical stimulation therapy for gastroesophageal reflux disease.

Electrical stimulation therapy (EST) of the lower esophageal sphincter is a relatively new technique for the treatment of gastroesophageal reflux disease (GERD) that may address the need of GERD patients, unsatisfied with acid suppressive medication and concerned with the potential risks of surgical fundoplication. In this paper we review available data about EST for GERD, including the development of the technique, implant procedure, safety and results from open-label trials. Two short-term temporary stimulation and long-term open-label human trials each were initiated to investigate the safety and efficacy of EST for the treatment of GERD and currently up to 2 years follow-up results are available. The results of EST are promising as the open-label studies have shown that EST is a safe technique with a significant improvement in both subjective outcomes of symptoms and objective outcomes of esophageal acid exposure in patients with GERD. However, long-term data from larger number of patients and a sham-controlled trial are required before EST can be conclusively advised as a viable treatment option for GERD patients.

Frequency of abnormal esophageal acid exposure in patients eligible for bariatric surgery

BackgroundObesity and gastroesophageal reflux disease (GERD) are both high-prevalence diseases in developed nations. Obesity has been identified as an important risk factor in the development of GERD. The objective of this study was to determine the frequency of abnormal esophageal acid exposure in patients candidate for bariatric surgery and its relationship with any clinical and endoscopic findings before surgery. MethodsData collected from a group of 88 patients awaiting bariatric surgery included a series of demographic variables and symptoms typical of GERD. The tests patients underwent included manometry, pH monitoring, and upper gastrointestinal endoscopy. Univariate and multivariate analyses were conducted on the variables related to the onset of reflux. ResultsEsophageal pH monitoring tests were positive in 65% of the patients. Manometries showed lower esophageal sphincter hypotonia in 46%, while 20% returned abnormal upper endoscopy results. Out of the 45% of patients who were asymptomatic or returned normal endoscopies, half returned positive esophageal pH tests. In turn, among the 55% of patients who had symptoms or an abnormal upper endoscopy, three quarters had pH tests that diagnosed reflux. pH tests were also positive in 80% of symptomatic patients and 100% of patients with esophagitis (P<.042). No statistically significant relationship was found between body mass index, sex, age, manometry, or hiatus hernia and the positive pH monitoring. ConclusionFrequency of abnormal esophageal acid exposure among obese patients is high. There is a relationship between the presence of symptoms and reflux. But the absence of symptoms does not rule out the presence of abnormal esophageal function tests.

Predictors of Abnormal Esophageal Acid Exposure in Patients with Eosinophilic Esophageal Infiltration

Predictors of Abnormal Esophageal Acid Exposure in Patients with Eosinophilic Esophageal Infiltration

Lower Esophageal Sphincter (LES) Electrical Stimulation Eliminates Proximal Esophageal Acid Exposure in Patients with Proximal GERD - One Year Results

Lower Esophageal Sphincter (LES) Electrical Stimulation Eliminates Proximal Esophageal Acid Exposure in Patients with Proximal GERD - One Year Results

Su1523 The Status of the Lower Esophageal Sphincter at Rest and the Degree of Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease

Su1523 The Status of the Lower Esophageal Sphincter at Rest and the Degree of Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease

Su1120 Histologic Features Do Not Reliably Distinguish the Presence or Absence of Pathologic Esophageal Acid Exposure in Patients With Dense Esophageal Eosinophilic Infiltration

Su1120 Histologic Features Do Not Reliably Distinguish the Presence or Absence of Pathologic Esophageal Acid Exposure in Patients With Dense Esophageal Eosinophilic Infiltration

Nonlinear Relationship Between Body Mass Index and Esophageal Acid Exposure in the Extraesophageal Manifestations of Reflux

Obesity is believed to be an important etiologic factor in gastroesophageal reflux disease. However, it is not clear how obesity might affect esophageal acid exposure in patients with extraesophageal manifestations of reflux. We conducted a cross-sectional study of 223 patients with extraesophageal symptoms suspected of being related to reflux. Participants underwent endoscopy and 48-hour wireless pH testing. The percentage of time at a pH of less than 4 (total, upright, and supine) was measured for each patient, and data were compared with corresponding body mass index (BMI), as continuous and categoric variables (normal, 18.5 to <25; overweight, 25 to <30; and obese, >30). Multivariable linear regression was used to identify variables associated with percentage of total time at a pH less than 4. The primary predictor of interest was BMI; age, sex, esophagitis, and hiatal hernia status were considered potential confounders or precision variables. Esophageal acid exposure was associated significantly (P < .001) with BMI. The percentage of time at a pH less than 4 and total symptomatic reflux events increased significantly (P = .005) with increasing BMI. The relationship between percentage of time at a pH less than 4 and BMI was nonlinear and S-shaped. With BMI ranges, the percentage of time at a pH less than 4 increased by 0.23% (normal BMI), 0.75% (overweight), and 0.07% (obese) for every 1-kg/m(2) increase in BMI (P < .001). Increases in esophageal acid exposure are greatest among overweight patients and plateau in obese patients. The findings have implications for benefit of weight loss in patients with suspected extraesophageal manifestations of gastroesophageal reflux disease.

The Ability of Histologic Features to Distinguish the Presence of Pathologic Esophageal Acid Exposure in Patients with Dense Esophageal Eosinophilic Infiltration

Purpose: The presence of histologic features has been suggested as discriminatory between dense esophageal eosinophilia attributable to allergic eosinophilic esophagitis (EoE) and gastroesophageal reflux (GERD). However, well designed comparative studies are lacking. The aim of this study is to prospectively assess the ability of histologic features to predict the presence of pathologic esophageal acid exposure in patients with esophageal eosinophilic infiltration. Methods: Forty patients with dysphagia and ≥15 eos per HPF on baseline esophageal biopsy who underwent 24-hour pH testing were studied in the absence of acid suppressing or steroid therapy. A minimum of 8 biopsies from the mid and distal esophagus were obtained. A histologic scoring system, illustrated in Table 1, was used by a single experienced, blinded pathologist (TCS) to assign a score to each patient and a clinical impression was made as to whether the findings were consistent with GERD or allergic EoE.Table 1: Histologic scoring systemResults: Of the 40 patients, 17 had pathologic esophageal acid exposure. The clinical impression by the pathologist was predictive of the presence or absence of pathologic acid reflux 70% of the time (Table 2). The histologic score was similar between patients with and without pathologic acid reflux. However, spongiosis was greater in patients without pathologic acid reflux. Grade 2 spongiosis was seen exclusively in allergic EoE, observed in 39% (9 of 23) of these patients (Table 2). The histologic score was not predictive of acid reflux, with ROC analysis yielding an area under the curve of 0.64 (Figure 1).Table 2: Predictive value of histologic features for esophageal eosinophiliaFigure 1: ROC Curve for Histologic Score.Conclusion: Histologic features and a histologic scoring system do not reliably predict the etiology of dense esophageal eosinophilic infiltration as determined by the presence or absence of abnormal acid exposure. However, spongiosis may discriminate between allergic and acid induced eosinophilia. Future studies may provide further discriminatory features between these two interrelated conditions.

Association of Eosinophilic Esophagitis and Persistent Esophagitis in Barrett's Esophagus

Background: The presence of basal cell hyperplasia, spongiosis, and other histologic features have been suggested to be discriminatory between dense esophageal eosinophilia attributable to allergic eosinophilic esophagitis (EoE) opposed to that attributable to gastroesophageal reflux (GERD). However, well designed comparative studies are lacking. Aim: To assess the ability of histologic features to predict the presence of pathologic esophageal acid exposure in patients with esophageal eosinophilic infiltration. Methods: Twelve patients with ≥ 15 eos per HPF on esophageal biopsy who underwent 24 hour pH testing and failed either acid suppressing or steroid therapy given based on pH results were studied. Esophagogastroduodenoscopy (EGD)was performed and 6mid and 6 distal esophageal biopsies was performed 6 weeks later. A histologic scoring system, illustrated in Table 1, was used by a single experienced, blinded pathologist (TCS) to assign a score to each patient and a clinical impression was made as to whether the findings were consistent with allergic EoE or GERD. The correlation between individual histologic features and GERDwas assessed using student's t-test while that between the histologic score and GERD was assessed using Fisher's exact test. Results: Of the 12 patients, 6 had pathologic esophageal acid exposure (Table 2). The density of esophageal eosinophils was higher in patients with an abnormal pH study compared to those with a normal pH study. The histologic score was similar between patients with and without pathologic acid reflux. The clinical impression of EoE by the pathologist was not predictive of the presence or absence of pathologic acid reflux. Conclusion: This study suggests that a histologic scoring system does not predict the etiology of dense esophageal eosinophilic infiltration as determined by the presence or absence of abnormal acid exposure. TABLE 1: Histologic Scoring System

Predictive Value of Histologic Features to Distinguish the Presence of Pathologic Esophageal Acid Exposure in Patients With Dense Esophageal Eosinophilic Infiltration

Predictive Value of Histologic Features to Distinguish the Presence of Pathologic Esophageal Acid Exposure in Patients With Dense Esophageal Eosinophilic Infiltration

Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease

ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects. To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD. This was a double-blind, placebo-controlled, multi-centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2-week baseline washout period was followed by 2-week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom-free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24-h impedance-pH monitoring was also determined in a subset of 24 patients. The full analysis set comprised 103 patients ADX10059 (N= 50), Placebo (N=53). In treatment week 2, ADX10059 significantly increased GERD symptom-free days (P=0.045) and heartburn-free days (P=0.037), reduced antacid use (P=0.017), improved total symptom score (P=0.048) including subscale heartburn/regurgitation (P=0.007) and sleep disturbance because of GERD (P= 0.022). ADX10059 significantly reduced total (P=0.034) and acidic reflux events (P=0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%). Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD.