Distal Acid Exposure Time Research Articles

Effect of Ketogenic Diet on Gastroesophageal Reflux Disease: Literature Review and Exploratory Study

Background: Management strategies for gastroesophageal reflux disease (GERD) include lifestyle changes, medications, and surgery. A very low carbohydrate diet (VLCD) may offer an effective treatment option. Thus, we aimed to evaluate the effects of a VLCD on GERD through a literature review and exploratory study. Methods: We performed a literature search using MeSH and free-text terms in MEDLINE, EMBASE, Cochrane, and Google Scholar to summarize the available evidence through March 2023. Furthermore, we conducted an exploratory study in patients with GERD and a BMI > 25 kg/m2 without prior antireflux surgery. The subjects followed a strict VLCD guided by a medical bariatrician for 4 weeks and completed periodical medical and laboratory evaluations. Descriptive and inferential statistics were applied to assess the covariates before and after intervention. Significance level (α) was set at .05. Results: We found 5 studies reporting the effects of a VLCD on GERD. All of them reported relief of GERD-related symptoms and a decrease in distal acid exposure time (AET) in the short term (6 days to 16 weeks) in most subjects. In our exploratory study, a VLCD reduced the mean BMI (32.2 ± 2.75 vs 30.4 ± 2.23 kg/m2, P = .022) and AET (10.8 ± 3.7 vs 5.5 ± 4.2%, P = .049) among the cohort. Moreover, the DeMeester score and number of proximal reflux episodes improved in 3 patients, and the GERD-Health Related Quality of Life score improved in all 4. Conclusions: Current evidence, including our exploratory study, suggests that a VLCD in overweight or obese patients with GERD may have significant immediate benefits. Further studies are warranted.

Feasibility and Efficacy of Magnetic Sphincter Augmentation for the Management of Gastroesophageal Reflux Disease Post-Sleeve Gastrectomy for Obesity

BackgroundPatients with medically intractable GERD after laparoscopic sleeve gastrectomy (LSG) have limited surgical options. Fundoplication is difficult post-LSG. Roux-en-Y gastric bypass may be used as a conversion procedure but is more invasive with potential for serious complications. Magnetic sphincter augmentation (MSA) is a less invasive GERD treatment alternative. The objective of this study was to assess safety and efficacy outcomes of MSA after LSG.MethodsThe primary outcome of this observational, multicenter, single-arm prospective study was the rate of serious device and/or procedure-related adverse events (AEs). The efficacy of the LINX device was measured comparing baseline to 12-month post-implant reductions in distal acid exposure, GERD-HRQL score, and average daily PPI usage.ResultsThirty subjects who underwent MSA implantation were followed 12 months post-implant. No unanticipated adverse device effects were observed. There were two adverse events deemed serious (dysphagia, pain, 6.7%) which resolved without sequelae. GERD-HRQL scores showed significant improvement (80.8%, P < 0.001), and reduction in daily PPI usage was seen (95.8%, P < 0.001). Forty-four percent of subjects demonstrated normalization or > = 50% reduction of total distal acid exposure time (baseline 16.2%, 12 months 11%; P = 0.038).ConclusionsPost-LSG, MSA showed an overall improvement of GERD symptoms, and reduction in PPI use with explants within anticipated range along with improvement in distal esophageal acid exposure time.Graphical

719 REDUCED MEAN NOCTURNAL BASELINE IMPEDANCE AIDS DIAGNOSIS OF GASTRO-ESOPHAGEAL REFLUX DISEASE AND LARYNGOPHARYNGEAL REFLUX DISEASE

Abstract Laryngopharyngeal reflux disease (LPR) and gastro-esophageal reflux disease (GERD) occur due to acidic gastric refluxate causing symptoms. Baseline esophageal impedance has been shown to be reduced with prolonged acid exposure. Mean nocturnal baseline impedance (MNBI) is a novel measure that has shown promise in GERD but has not been evaluated in LPR. This study aimed to assess the role of MNBI in LPR and GERD patients. Methods Off-therapy impedance-pH tracings were blindly reviewed for 187 patients previously prospectively allocated clinical diagnoses of LPR (n = 105) or GERD (n = 82). Conventional impedance-pH measures and MNBI were analysed for the two groups. Results MNBI was significantly lower in the distal esophagus in GERD patients compared with LPR (1679 ± 914 vs. 2109 ± 863; p = 0.001). Similarly, in the proximal esophagus, MNBI was lower in GERD than LPR (2289 ± 579 vs. 2541 ± 471; p = 0.001). In the pharynx, MNBI was similar between the two groups (2116 ± 699 vs. 2133 ± 770; p = 0.878). Distal acid exposure time (AET) and the number of distal acid reflux episodes negatively correlated with distal esophageal MNBI (r = −0.195; p = 0.007) and (r = −0.330; p &amp;lt; 0.001) respectively. Conclusion Baseline impedance was reduced in both LPR and GERD at both distal and proximal esophageal measurements, and more severely reduced in GERD. Baseline impedance is strongly and inversely related to acid exposure in the esophagus. Pharyngeal MNBI was not reduced or different between groups. Distal and proximal esophageal MNBI may be useful in diagnosis of LPR as well as GERD.

Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease.

BackgroundEsophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms.MethodsIn this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson’s correlation or Spearman’s rank coefficients.Results70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= −0.5 to −0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms.ConclusionsConcordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.

The Lyon Consensus: Does It Differ From the Previous Ones?

Gastroesophageal reflux disease (GERD) is a complex disorder with heterogeneous symptoms and a multifaceted pathogenetic basis, which prevent a simple diagnostic algorithm or any categorical classification. Clinical history, questionnaires and response to proton pump inhibitor (PPI) therapy are insufficient tools to make a conclusive diagnosis of GERD and further investigations are frequently required. The Lyon Consensus goes beyond the previous classifications and defines endoscopic and functional parameters able to establish the presence of GERD. Evidences for reflux include high-grade erosive esophagitis, Barrett’s esophagus, and peptic strictures at endoscopy as well as esophageal acid exposure time > 6% on pH-metry or combined pH-impedance monitoring. Even if a normal endoscopy does not exclude GERD, its combination with distal acid exposure time < 4% on off-PPI pH-impedance monitoring provides sufficient evidence refuting this diagnosis. Reflux-symptom association on pH-monitoring provides supportive evidence for reflux-triggered symptoms and may predict a better treatment outcome, when present. Also recommendations to perform pH-impedance “on” or “off” PPI are well depicted. When endoscopy and pH-metry or combined pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (eg, microscopic esophagitis), high-resolution manometry (ie, ineffective esophagogastric barrier and esophageal body hypomotility), and novel impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index, can contribute to better identify patients with GERD. Definition of individual patient phenotype, based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the esophagogastric junction, and clinical presentation, will lead to manage GERD patients with a tailored approach chosen among different types of therapy.

378 Resting Upper Esophageal Sphincter Pressure Is Elevated in Proton Pump Inhibitor-Refractory Chronic Cough Patients and May Be a Marker for Laryngeal Hypersensitivity

INTRODUCTION: Chronic cough is difficult to treat when unresponsive to proton-pump inhibitor (PPI) and sinus therapy. In this setting it is presumed to be neurogenic in etiology. Despite the role of the upper esophageal sphincter (UES) as a barrier to laryngopharyngeal reflux disease, it has not been well characterized in chronic cough patients. We aim to assess UES tonicity in patients with PPI-refractory chronic cough and otherwise intact esophageal motor function. METHODS: Patients with a Chicago Classification diagnosis of normal esophageal motility on high-resolution esophageal manometry (HRM) on studies performed for the indication of chronic cough were retrospectively studied. All studies were performed at a GI motility lab at a tertiary care center from January 2013 to August 2018. Patients with prior cervical spinal surgery, foregut surgery, gastroparesis, severe pulmonary disease or manometric hiatal hernia were excluded. All HRM were performed with a solid-state assembly with a 4.2 mm outer diameter catheter. Upper esophageal resting pressure and residual pressure (mmHg) were recorded from HRM studies and compared to a control group of patients with normal esophageal motility on studies performed for an indication of non-cardiac chest pain. Available pH-metry tests in chronic cough patients were also reviewed for acid exposure time. RESULTS: Fourteen patients with chronic cough (mean age 63 ± 25, 71% female) and twenty patients with non-cardiac chest pain (mean age 55 ± 14, 60% female) were included. Median resting UES pressure (mmHg) was higher in the chronic cough group (80) vs the chest pain group (50.8) with a p value of 0.004 (Figure 1). There was no difference in residual UES pressure (3.5 in chronic cough vs 3.15 in chest pain). A total of 12 pH studies were performed in chronic cough patients; 9 of these were on PPI. Median distal acid exposure time % was 1.35 [IQR 0.5-6]. CONCLUSION: UES hypertonicity found in PPI-refractory chronic cough patients may be a marker of laryngeal hypersensitivity. A second possibility is that primary UES dysfunction is the cause of cough in this subgroup.

365 The Prevalence and Clinical Significance of Esophageal Motility Disorders in Patients Presenting With Laryngopharyngeal Reflux (LPR) Symptoms

INTRODUCTION: Esophageal motor dysfunction may underlie impaired bolus and refluxate clearance in laryngopharyngeal reflux (LPR). However, the prevalence of co-existing esophageal dysmotility and correlation with reflux parameters and symptoms in LPR is unknown. METHODS: We conducted a retrospective study of consecutive patients with suspected LPR referred for high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance and pH testing (HEMII-pH) at a tertiary center in 3/2018-5/2019. Validated symptom surveys were prospectively collected at the time of testing, including Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Questionnaire (GERD-Q), and 12-item short-form health survey (SF-12). HRM findings were categorized using the Chicago Classification v3.0. Statistical analyses were performed using ANOVA or Fisher’s exact test. RESULTS: 113 patients (64% female, mean age 54.9 years) were included, with 52 (46%) having abnormal findings on HRM. The most common diagnosis was ineffective esophageal motility (IEM) [n = 37 (32.7%)]. 19 (16.8%) patients were found to have either a disorder of esophagogastric junction (EGJ) outflow or a major disorder of peristalsis, of which EGJ outflow obstruction (EGJOO) was the most prevalent diagnosis [n = 11 (9.7%)] (Table 1). With the exception of increased distal acid exposure time (AET) among patients with hypercontractile motility disorders (9% vs 2% in patients with normal HRM, P = 0.03), there were no differences in pharyngeal bolus reflux events, total bolus reflux events on impedance, and AET across HRM findings. Reporting throat symptoms as a primary complaint on presentation was associated with greater odds of having abnormal HRM compared to esophageal symptoms alone (OR 5.5, P = 0.005) (Figure 1). However, the presence and specific type of motility disorder were not associated with symptom severity as measured on RSI, GERD-Q, or health-related quality of life on the SF-12. CONCLUSION: Esophageal motility disorders are prevalent among patients with suspected LPR symptoms, including up to one of six with either a disorder of EGJ outflow or major disorder of peristalsis. Patients with these conditions are more likely to report throat symptoms as a primary complaint. However, there was no correlation between HRM findings and symptom severity. The role of esophageal motor dysfunction in patients with LPR symptoms remains to be further defined.

Ambulatory pH-impedance-pressure monitoring as a diagnostic tool for the reflux–cough syndrome

Gastroesophageal reflux is considered to be a significant contributing factor to chronic unexplained cough. Patients are often presumed to have reflux-induced cough and are exposed to high-dose and long-term empirical therapy with proton pump inhibitors (PPIs) despite the limited treatment efficacy in this population. We aimed to assess the diagnostic value of 24-hour ambulatory pH-impedance-pressure monitoring for the diagnosis of reflux-induced chronic cough. In this multicenter study, we evaluated 192 patients with chronic cough using 24-hour pH-impedance-pressure monitoring off PPIs. Manometry was used to detect all cough bursts while pH-impedance allowed for the evaluation of all reflux episodes, including weakly acidic reflux. The symptom association probability was used to determine a temporal relationship between reflux and cough. A diagnosis of reflux-induced cough was made in 25.5% of the patients. If only acid reflux episodes were used, 22.4% of those patients would not have been diagnosed. Significantly more patients with reflux-induced cough had typical reflux symptoms (P=0.031) and a pathological distal acid exposure time (P=0.025) in comparison to patients without the diagnosis. A diagnosis of cough-induced reflux was made in 24.0% of the patients. Only 59% of all cough bursts were registered by the patients. Overall, only approximately one quarter of patients with chronic unexplained cough have reflux-induced cough, explaining the observation that the vast majority of patients with chronic cough do not benefit from antireflux therapy. pH-impedance-pressure monitoring helps to identify patients who are likely to have reflux as a cause of their chronic cough.

Symptom analysis improves GERD diagnosis and may be helpful to define a successful surgical approach

We read with interest the article by Koch et al. [1] that randomly allocated 125 patients with documented chronic gastroesophageal reflux disease (GERD) to either laparoscopic floppy Nissen fundoplication (n = 62) or laparoscopic Toupet fundoplication (n = 63). Both procedures proved to be equally effective in improving quality of life and both typical and atypical reflux-related symptoms. The authors also indicated that laparoscopic Toupet fundoplication was characterized to have a high ability to belch and a reduced rate of postoperative dysphagia. The authors opted to use the current gold standard for GERD diagnosis (i.e., impedance-pH testing), and thus, they carefully and objectively defined the inclusion criteria for undergoing surgical fundoplication [2]. Indeed, they considered patients for surgery who had a total number of refluxes higher than 73 per 24 h, a DeMeester score higher that 14.7, or a positive association between symptoms and reflux events by means of the symptom index (SI). One-year postsurgery impedance-pH studies clearly showed a marked decrease of reflux episodes (total, acid, proximal, upright, and recumbent refluxes) and a DeMeester score that paralleled the large improvement of GERD symptoms and quality of life, thus supporting the usefulness of impedance-pH testing in selecting GERD patients for surgery [3]. However, even though this study provides relevant novel data on the potential application of impedance-pH technology for the surgical management of GERD patients, we believe that the interpretation of their findings would be improved if the results of symptom association analysis after surgery were also reported. Few data are reported about SI (i.e., only preoperative information, and without describing whether the association was positive for acid and/or nonacid reflux episodes), and no data are provided for symptom association probability (SAP), which is considered by several authors to be the best index demonstrating an association between symptoms and reflux events. Indeed, SAP is based on statistical parameters, is not generated by chance, and clearly explores the relationship between symptoms and refluxes [4]. Although SI has the advantage of being easy to calculate, it does not take into account the total number of reflux episodes with the likelihood risk that a symptom is found to be associated with reflux by chance [5]. Therefore, because impedancepH permits the measurement of all types of reflux and correlates them to symptoms, it increases the diagnostic yield by using a symptom association analysis mode such as SI or SAP [6–10]. In fact, previous studies have shown that GERD patients, particularly those found to have no mucosal injuries at upper endoscopy, frequently have a normal distal acid exposure time and therefore a low acidrelated DeMeester score [3, 11]. Using these parameters, it has been observed that GERD patients have symptoms associated not only with acid reflux but also with weakly acidic reflux; this may explain the increased proton pump inhibitor failure observed in endoscopy-negative patients [3, 12], thus supporting the use of alternative surgical or endoscopic therapies in this patient population [13, 14]. So far, data concerning the SI and SAP for acidic and weakly acidic reflux should be reported in order to know whether N. de Bortoli (&) I. Martinucci S. Marchi Gastroenterology Unit, Department of Translational Medicine and New Technology, University of Pisa, Pisa, Italy e-mail: nick.debortoli@gmail.com

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease

Introduction Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. Aim To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. Methods Consecutive endoscopy-negative patients treated with proton pump inhibitors ( n = 219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. Results Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP−, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP−, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. Conclusion Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients.

Characteristics of Reflux Episodes and Symptom Association in Patients With Erosive Esophagitis and Nonerosive Reflux Disease: Study Using Combined Impedance–pH Off Therapy

We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs). Patients with EE and NERD underwent combined impedance-pH monitoring. Normal values were defined on the basis of previously collected data from 48 HVs. We evaluated distal esophageal acid exposure time (AET), number and type of reflux episodes (acid, nonacid), acid and bolus clearance times, proximal extension of reflux episodes, and symptom association probability (SAP). Distal AET (percentage time, pH<4) was higher (P<0.01) in 58 EE patients (median 7.4%, 25-75th percentile 4.2-9.9%) compared with 168 NERD patients (4.2% (1.2-6.4%)) and 48 HVs (0.7% (0.2-1.4%)). Patients with EE and NERD had a higher (P<0.01) number of acid reflux episodes compared with HVs (51 (37-66) vs. 34 (22-51) vs. 17 (8-31); P<0.05), but a similar number of nonacid reflux episodes (22 (15-39) vs. 23 (15-38) vs. 18 (14-26); P=NS). The percentage of reflux episodes reaching the proximal esophagus was higher (P<0.01) in EE patients (57% (45-73%)) than in NERD patients (45% (36-60%)) and HVs (33% (19-46%)). A positive SAP for heartburn or regurgitation was found in 161 of 168 (96%) NERD and 54 of 58 (93%) EE patients (P=NS). Acid reflux episodes, volume, and acid clearance are important factors in the pathogenesis of reflux-induced lesions. Nonacid reflux contributes less to esophageal mucosa damage, but is involved in the development of reflux symptoms in both NERD and EE patients.