Number Of Nonacid Reflux Episodes Research Articles

Identification of Different Phenotypes of Esophageal Reflux Hypersensitivity and Implications for Treatment

Reflux hypersensitivity (RH), a functional esophageal disorder, is detected in 14%-20% of patients who present with typical esophageal symptoms. As many as 40% of patients with RH do not respond to treatment with pain modulators or proton pump inhibitors (PPIs); behavior disorders might contribute to lack of treatment efficacy. We aimed to assess the prevalence of behavioral disorders and their effects on typical reflux symptoms in patients with RH. We performed a retrospective study of 542 patients with PPI-refractory esophageal symptoms (heartburn, regurgitation, or chest pain) or with symptoms that responded to PPI therapy, evaluated for anti-reflux surgery from January 2016 through August 2019 at a single center in London, United Kingdom. We collected data on symptoms, motility, and impedance-pH monitoring and assigned patients to categories of RH (n = 116), functional heartburn (n = 126), or non-erosive reflux disease (n = 300). Of the 116 patients with a diagnosis of RH, 59 had only hypersensitivity, whereas 57 patients (49.2%) had either excessive supragastric belching (SGB, 39.7%), based on 24-hour impedance-pH monitoring, or rumination (9.5%), based on postprandial manometry combined with impedance. The prevalence of SGB and rumination in patients with RH was significantly higher than in patients with functional heartburn (22%; P < .001). Patients with RH and rumination were significantly younger (P = .005) and had the largest number of non-acid reflux episodes (P = .023). In patients with RH with SGB, SGB episodes were associated with 40.6% of marked reflux symptoms (heartburn, regurgitation, or chest pain), based on impedance-pH monitoring. In patients with RH and rumination, 40% of reflux-related symptoms (mostly regurgitation) were due to possible rumination episodes. Almost half of patients with a diagnosis of RH have behavior disorders, including excessive SGB or rumination. Episodes of SGB or rumination are associated with typical reflux symptoms. Segregation of patients with diagnosis of RH into those with vs without behavioral disorders might have important therapeutic implications.

Acid and nonacid gastroesophageal reflux after single anastomosis gastric bypass. An objective assessment using 24-hour multichannel intraluminal impedance-pH metry

BackgroundSingle anastomosis gastric bypass (SaGB) was introduced in 2001 as an alternative to “loop” gastric bypass. It was considered as a procedure that would eliminate alkaline reflux and associated esophagitis. ObjectivesExisting evidence about the postoperative incidence of gastroesophageal reflux (GERD) after SaGB is based on studies using symptom questionnaires. The aim of our study was to evaluate GERD 12 months after SaGB by using 24-hour multichannel intraluminal impedance pH metry (24-h MIIpH). SettingSurgical department of a university hospital MethodsMorbidly obese candidates for SaGB underwent 24-hour MIIpH prior and 12 months after their bariatric procedure. ResultsThere were 11 patients included in this prospective study. Results of 24-hour MIIpH revealed that DeMeester score (40.48 versus 24.16, P = .339) had an increasing trend 12 months after SaGB. Acid reflux episodes decreased, whereas nonacid reflux episodes increased postoperatively, both in proximal and distal esophagus. Total median bolus clearance time and acid clearance time increased. De novo GERD developed in 2 patients (28.6%) and worsening of already existing GERD developed in all patients with preoperative evidence of GERD. ConclusionThe use of symptom questionnaires to assess postoperative GERD after SaGB may not accurately depict the real image. Twenty-four–hour MIIpH in 12 months after SaGB revealed an increase of total number of nonacid reflux episodes and a decrease of total number of acid reflux episodes, with longer duration of each acid reflux episode. Close postoperative follow-up with reflux testing and possibly endoscopy could eliminate the risk of complicated GERD.

Detection of gastroesophageal reflux in children with cerebral palsy using combined multichannel intraluminal impedance-ph procedure.

Gastroesophageal reflux (GER) is a very common condition in children with neurological impairment and this can influence nutritional and respiratory outcomes. The aim of this study was to investigate the presence of GER in children with cerebral palsy (CP) using multiple intraluminal impedance (MII)-pH monitoring. The use of combined MII-pH allows for the detection of both acid and non-acid reflux episodes. A total of 29 CP patients with symptoms suggesting GER, aged 2 to 10 years old, underwent 24-hour combined MII-pH monitoring. There were a total of 3899 reflux episodes, of which 29% were acid, 60% were weakly acid and 11% were alkaline. The number of non-acid reflux episodes was statistically significantly greater (p < 0.01). These findings confirm that GER disease is seen frequently in children with cerebral palsy and most of the reflux episodes are not acidic. Non-acid reflux can also influence the morbidity in patients with cerebral palsy. It can be concluded that 70% of the reflux episodes would not have been recognized by pH measurement alone.

Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy: Is gastroparesis a factor?

To determine whether an increased number and duration of non-acid reflux events as measured using the multichannel intraluminal impedance pH (MII-pH) is linked to gastroparesis (GP). A case control study was conducted in which 42 patients undergoing clinical evaluation for continued symptoms of gastroesophageal reflux disease (both typical and atypical symptoms) despite acid suppression therapy. MII-pH technology was used over 24 h to detect reflux episodes and record patients' symptoms. Parameters evaluated in patients with documented GP and controls without GP by scintigraphy included total, upright, and supine number of acid and non-acid reflux episodes (pH < 4 and pH > 4, respectively), the duration of acid and non-acid reflux in a 24-h period, and the number of reflux episodes lasting longer than 5 min. No statistical difference was seen between the patients with GP and controls with respect to the total number or duration of acid reflux events, total number and duration of non-acid reflux events or the duration of longest reflux episodes. The number of non-acid reflux episodes with a pH > 7 was higher in subjects with GP than in controls. In addition, acid reflux episodes were more prolonged (lasting longer than 5 min) in the GP patients than in controls; however, these values did not reach statistical significance. Thirty-five patients had recorded symptoms during the 24 h study and of the 35 subjects, only 9% (n = 3) had a positive symptom association probability (SAP) for acid/non-acid reflux and 91% had a negative SAP. The evaluation of patients with a documented history of GP did not show an association between GP and more frequent episodes of non-acid reflux based on MII-pH testing.

Sa1377 Impedance Testing Understimates Acid Reflux by Discounting Duration of Bolus Exposure

perception during 2h periods after ingestion were evaluated: 1) Coke® (carbonated, pH 2.5, caffeine 2.9 mg/oz.) [B1]; 2) Ciel® mineralized water (carbonated, pH 5.5, no caffeine) [B2]; and 3) Lipton® lemon ice tea (non-carbonated, pH 3.7, caffeine 2.5 mg/oz.) [B3].To evaluate GER activity we performed esophageal impedance-pH monitoring and number of reflux episodes (pH < 4), percentage of time of esophageal pH < 4 (%), number of acid and non-acid reflux, heartburn, regurgitation and belching episodes were analyzed during the 2-h pH period Data were analyzed with ANOVA, t test and Friedman test. Results: There was no difference in age (p=0.17), gender (p=0.441) or BMI (p=0.826) between groups. In all of them carbonated beverages (B1 and B2) showed greater number of non-acid reflux episodes (NAR, Table 1) and induce more belching episodes but not more heartburn and regurgitation. Caffeinated non-carbonated beverage (B3) was more associated with acid reflux, longer reflux episodes and more ph < 4 time (p<0.05). HV, EE and NERD subjects had similar findings after consumption of the 3 beverages. However, FH patients had different and non-expected findings such more belching after consumption of B3 (non-carbonated beverage) Conclusions.Based in our results there is no evidence that carbonated beverages induces more GERD symptoms in EE and NERD when compared to controls. Findings in FH subjects confirm that in these patients symptom perception could be related to psychological factors such as hypervigilance or anxiety. Finally, in clinical practice it is important to consider GERD phenotype, gas quantity and acidity grade in a beverage before recommending its consumption or not. Effects of carbonated beverages among groups

A Novel Partial 5HT3 Agonist Pumosetrag after a Standard Refluxogenic Meal Reduces Acid Reflux Events in GERD Patients: A Randomized, Double-Blind, Placebo-Controlled Pharmacodynamic Study

Purpose: Transient lower esophageal sphincter relaxations (TLESRs) are a major cause of gastro-esophageal reflux disease (GERD). Pumosetrag, a selective partial agonist at 5HT3 receptors, increases LES pressure and gastrointestinal motility in experimental animal models. In a previous study, it was shown to reduce the rate of reflux episodes after a refluxogenic meal in healthy subjects. Aims: To evaluate the effect of pumosetrag on esophageal related pharmacodynamic measurements, including changes in reflux episodes, lower esophageal sphincter pressure, and specific symptoms (heartburn, regurgitation, acid taste) in GERD patients receiving a refluxogenic meal, and to assess the safety and tolerability of pumosetrag. Methods: A randomized, double-blind, placebo-controlled study evaluated the pharmacodynamic effects of pumosetrag. Subjects were randomized to one of three dose levels of pumosetrag (0.2 mg, 0.5 mg, or 0.8 mg) or placebo. Before and after 7 days of treatment, GERD patients underwent manometry, and intraesophageal multichannel intraluminal impedance and pH (MII-pH) after a standard refluxogenic meal (a sausage-and-egg based meal [300 kCal, 60% fat] with eight ounces of Hershey's chocolate milk). Intent to treat analysis of covariance models were used to assess treatment effects. For evaluating the safety and tolerability of pumosetrag, each subject was monitored from the time of the first dose of study medication until the end of the study. Results: A total of 223 GERD patients (125[56%] females, mean [SD] age = 36[12] years) were enrolled. No overall treatment effects were detected for the total number of reflux episodes (p>0.5); however, significant treatment effects (p<0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared to placebo (13.3 ± 1.1) (Table). Significant treatment effects (p<0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8mg (10%) compared to placebo (16%). Differences in LESP (p>0.5), the number of nonacid reflux episodes after a refluxogenic meal (p>0.15), and specific symptom scores (p>0.4) were not detected (table). No serious adverse events on pumosetrag were reported.Table: Table. Reflux events, post-treatment mean LESP, and proportion time with pH < 4 (mean±SEM unless otherwise noted)Conclusion: In GERD patients, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events and proportion of time that pH <4 after a refluxogenic meal challenge, but did not affect the total number of reflux episodes or LES pressure. The results of the study suggest pumosetrag has effects on some pharmacodynamic endpoints associated with GERD and is worthy of additional study. Supported by Edusa Pharmaceuticals, Inc, Princeton, NJ. Disclosure: All authors - Grant research support from Edusa Pharmaceuticals, Inc.

Gastroparesis is Not Associated with Acid or Non-Acid Reflux

Purpose: Gastroparesis (GP) may often be misdiagnosed as gastroesophageal reflux disease (GERD) given the similarity in symptoms of regurgitation related to high volume reflux. Prior studies have suggested an association between delayed stomach emptying and refractory GERD. Unfortunately, unlike GERD, the symptoms of GP do not respond to acid suppression therapy. Whether non-acid reflux contributes to this lack of symptom improvement in patients with GP is unknown. Our study aims to determine whether an increased number and duration of acid and non-acid reflux episodes as measured using the Multichannel Intraluminal Impedance pH (MII-pH) is seen in patients with GP as compared to controls. Methods: The baseline characteristics, MII-pH data and gastric emptying scintigraphy (GES) results were reviewed on 40 consecutive patients undergoing clinical evaluation for continued heartburn and regurgitation despite acid suppression therapy. All enrolled subjects were continued on their PPI for the duration of the study. The 8 channel MII-pH probe recorded impedance data at 3, 5, 7, 9, 15 and 17 cm above the LES and pH data 5 cm above and 10 cm below the LES. The MII-pH parameters evaluated were as follows: total, supine and upright number of acid reflux episodes (pH <4); total, supine and upright number of non-acid reflux episodes as defined by pH >4; duration of acid and non-acid reflux in 24 hour period and the number of reflux episodes lasting over 5 minutes. GES results were reviewed with a normal study defined by gastric emptying half-time of 45-90 minutes. The control group (n=25, 6M, 19F, mean age 51) consisted of subjects with symptoms of regurgitation on PPI therapy and a normal GES, and the GP group (n=15, 4M, 11F, mean age 54) consisted of those subjects with an abnormal GES and/or history of GP. Results: Using SAS software, the impedance parameters listed above were compared between patients with GP and controls. The t-test for equality of the mean showed no statistical difference between the two groups with respect to the total number or duration of acid reflux events (p value=0.9), total number and duration of non-acid reflux events (p value=.6) or the duration of longest reflux episodes (p value=.5). The number of non-acid reflux events with pH >7 was slightly higher in the GP group than the controls (mean=5.47 ± 5.2 versus mean=4.84 ± .6.0, p value=0.7). Conclusion: Despite previous studies suggesting an association between refractory GERD and GP, we did not find increased reflux duration or increased number of reflux episodes in patients with GP. We conclude that delayed gastric emptying is not associated with either acid or nonacid reflux.

Gastroesophageal reflux disease and eosinophilic esophagitis in infants and children. A study of esophageal pH, multiple intraluminal impedance and endoscopic ultrasound

Objective. Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) in childhood share aspects of symptomatology. In order to characterize EE and GERD in infants and children with symptoms of GERD we performed a prospective investigation including prolonged esophageal pH measurement, multiple intraluminal impedance (MII) and esophageal wall estimation by endoscopic ultrasound (EUS). Material and methods. Infants and children (0–15 years) with typical symptoms of GERD persisting after a 14-days proton pump inhibitor trial were included in a prospective study protocol. Upper endoscopy and EUS of the esophageal wall were performed followed by combined esophageal MII and pH measurement for 24 h. Results. A total of 78 infants and children were investigated: EE patients (n = 6), GERD patients (n = 28) and a group of infants and children with normal investigations (n = 44). The GERD group did not show a significantly higher number of non-acid reflux episodes (p = 0.9) than the patients with normal investigations. In all patients gastroesophageal reflux regularly extended into the proximal esophagus. EUS in four EE patients suggested an increased thickness of the mucosal layers both in the distal and in the proximal part of the esophagus. Conclusions. Esophageal MII indicated that neutral non-acid reflux episodes do not occur frequently in pediatric GERD or in EE. MII and pH-metry indicated that the majority of reflux episodes both in patients and controls pass into the proximal esophagus. EUS measurements suggested in EE patients a thickened mucosa both in the proximal and the distal part of the esophagus as compared to children with GERD and disease controls.

Inter-observer agreement for multichannel intraluminal impedance-pH testing

Twenty-four-hour ambulatory multichannel intraluminal impedance (MII)-pH detects both acid and nonacid reflux (NAR). A computer-based program (Autoscan™, Sandhill Scientific, Highlands Ranch, CO, USA) automates the detection of reflux episodes, increasing the ease of study interpretation. Inter-observer agreement between multiple reviewers and with Autoscan™ for the evaluation of significant NAR with MII-pH has not been studied in the adult population. Twenty MII-pH studies on patients taking a proton pump inhibitor twice daily were randomly selected. Autoscan™ analyzed all studies using the same pre-programmed parameters. Four reviewers interpreted the MII-pH studies, adding or deleting reflux episodes detected by Autoscan™. Positive studies for NAR and total reflux episodes were based on published criteria. Cohen's kappa statistic (κ) evaluated inter-observer agreement between reviewers and Autoscan™ analysis. The average κ for pathologic NAR between reviewers was 0.57 (0.47-0.70), and between reviewers and Autoscan™ was 0.56 (0.4-0.8). When using the total reflux episode number as a marker for pathologic reflux (acid and NAR), the κ score was 0.72 (0.61-0.89) between reviewers, and 0.74 (0.53-0.9) when evaluating total reflux episodes. Two reviewers agreed more often with each other and with Autoscan™ on the number of NAR episodes, while the other two reviewers agreed with each other, but did not agree with either Autoscan™ or the first two reviewers. Inter-observer agreement between reviewers and Autoscan™ for detecting pathologic NAR is moderate, with reviewers either excluding more of the Autoscan™-defined events or excluding fewer events and therefore agreeing with Autoscan™.

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.

Effects of Endoscopic Full-Thickness Plication On GERD Measured By Multichannel Intraluminal Impedance Monitoring

Background: Endoscopic full-thickness plication (Plicator®) has been shown to be effective at controlling reflux symptoms and esophageal acid exposure in a recently published prospective randomized, sham-controlled trial. By means of multichannel intraluminal impedance monitoring (MII), detection of nonacid or weakly acidic reflux events, aerophagia, and differentiation of true reflux events from non-reflux events is possible. In this study, the effects of endoscopic full-thickness plication measured by MII was analysed. Patients and Methods: 11 patients requiring maintenance proton pump inhibitor therapy underwent endoscopic full-thickness plication for treatment of gastro-esophageal reflux disease (GERD). MII was performed off-medication before and 6 month after endoscopic full-thickness plication in all patients. The effect of endoscopic full-thickness plication on acid, nonacid and weakly acidic reflux events were assessed. Results: 11 patients underwent endoscopic full-thickness plication using two or three serially placed Plicator implants. The mean number of total reflux and acid reflux episodes significantly decreased after the procedure (123 vs. 63, p < 0.02, 75 vs. 37, p < 0.02. The mean acid exposure time significantly decreased after treatment (124 min. vs. 41 min., p < 0.01). Total reflux exposure time and the mean DeMeester score significantly decreased after treatment (9.2% vs. 2.9%, p < 0.01, 27 vs. 9, p < 0.01).). The mean number of non-acid reflux episodes were not significantly decreased after the procedure (48 vs. 26, p = 0.306). The median bolus clearance time was not significantly changed (12 sec. vs. 11 sec. p = 0.798). Conclusions: Evaluation of endoscopic full-thickness plication efficacy by MII showed significant reduction in the mean number of total reflux episodes, acid reflux episodes and total reflux exposure time. Furthermore, the mean DeMeester score and the mean total acid exposure time in the distal esophagus were significantly decreased. No significant decrease was measured for non-acid reflux episodes or the median bolus clearance time.

Altered Esophageal Motility and Gastroesophageal Barrier in Patients with Jejunal Interposition After Distal Esophageal Resection for Early Stage Adenocarcinoma

IntroductionLimited resection of the esophagogastric junction has been proven to be safe and oncologically radical in patients with early esophageal cancer. Reconstruction with interposition of isoperistaltic jejunal loop (Merendino procedure) is supposed to prevent gastroesophageal reflux and therefore the recurrence of intestinal metaplasia at the anastomosis. The aim of this study was to assess the frequency of acid and nonacid refluxes after Merendino procedure using multichannel intraluminal impedance-pH (MII-pH) monitoring. Patients and MethodsBetween 2002 and 2005, 12 patients with esophageal adenocarcinoma underwent limited resection and jejunal interposition. Ten patients agreed to undergo a Gastrointestinal Symptom Rating Scale assessment, upper gastrointestinal (GI) endoscopy, esophageal manometry, and combined 24-h MII-pH monitoring more than 10 months postoperatively. ResultsPostoperatively, 4 (40%) patients reported belching without heartburn or acid regurgitation, 3 of them having a positive symptom index during 24-h MII-pH monitoring. Upper GI endoscopy revealed no inflammation, metaplasia, or stenosis at the esophagojejunal anastomosis. Esophageal manometry showed ineffective esophageal motility in four of ten patients. Combined 24-h MII-pH monitoring revealed normal distal esophageal acid exposure (% time pH < 4: 0.1% [0–1.5]), normal number of acid reflux episodes (3 [0–11]) but a high number of nonacid reflux episodes (82 [33–184]). Overall, eight patients revealed an abnormal number of nonacid reflux episodes. ConclusionThe limited resection with jejunal interposition for early esophageal cancer is efficient in controlling acid but not nonacid reflux. While the clinical relevance of nonacid reflux in the recurrence of Barrett’s esophagus is currently unknown, endoscopic surveillance should be considered in these patients.

Reproducibility of 24-Hour Combined Multiple Intraluminal Impedance (MII) and pH Measurements in Infants and Children. Evaluation of a Diagnostic Procedure for Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common disease in infants and children. Prolonged (24-hr) pH monitoring in the esophagus for determination of increased acid exposure has, together with endoscopy, been the only routinely implemented method for GERD diagnosis. The recently introduced multiple intraluminal impedance (MII) provides additional information about the number of both acid and nonacid episodes of retrograde bolus movement in the esophagus. The aim of this study was to investigate the day-to-day reproducibility and the interobserver variability of 24-hr combined MII (number of nonacid and acidic reflux episodes) and pH in the esophagus in infants and children. Upper endoscopy followed by 2 x 24-hr consecutive combined MII and pH monitoring was performed in 33 infants and children referred to a tertiary center for evaluation of GERD. The study was performed in a hospital setting without dietary restrictions. Bland-Altman difference versus mean plots and calculation of the limits of agreement (LOA) were used for assessment of the reproducibility of the total number of acidic and nonacidic reflux episodes. LOA for the number of acidic reflux episodes on day 2 were 0.2-5.3 times the value obtained on day 1. For the total number of nonacidic reflux episodes, LOA were 0.04-8.6; for the total number of reflux episodes, 0.3-3.3. An abnormal reflux index on one or both recording days was found in 7 of 30 patients. In conclusion, considerable day-to-day variability was found for nonacidic reflux episodes. Less variability was found for acidic reflux episodes. This variability must be taken into consideration for the use of MII in the clinical evaluation of infants and children with GERD.