Gastroesophageal Reflux Events Research Articles

The Irritable Infant in the Neonatal Intensive Care Unit: Risk Factors and Biomarkers of Gastroesophageal Reflux Disease

To determine risk factors for arching/irritability in high-risk infants and examine the significance of comorbidity and gastroesophageal reflux (GER) characteristics. Retrospective analysis of 24-hour pH-impedance studies of symptomatic infants in a neonatal intensive care unit (ICU) (n=516, 30.1±4.5weeks of gestation, evaluated at 41.7±3.2weeks postmenstrual age) was conducted. Comparisons were made between infants with >72 vs ≤72 arching/irritability events per day. We characterized risk factors for arching/irritability along with clinical, pH-impedance, and outcome correlates. Of 39 973 arching/irritability events and 42 155 GER events, the averages per day were 77.6±41.0 and 81.7±48.2, respectively. Acid reflux and impedance bolus characteristics were not significantly different between infants with >72 and≤72 arching/irritability events (P≥.05). The odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for postmenstrual age and weight at evaluation were significant for risk factors of preterm birth (2.3 [1.2-4.4]), moderate or severe neuropathology (2.0 [1.1-3.6]), and presence of oral feeding at testing (1.57 [1.07-2.30]). Acid GER disease is unlikely the primary cause of arching/irritability and empiric treatment should not be used when arching/irritability is present. Prematurity and neurologic impairment may be more likely the cause of the arching/irritability. Arching/irritability may not be a concern in orally fed infants.

Esophageal pH-monitoring in nonbrachycephalic dogs; a reference.

To establish parameters that describe acidic gastroesophageal reflux (GER) events in nonbrachycephalic, hospitalized dogs without gastrointestinal disease following short total intravenous anesthesia, to establish upper reference limits for parameters that describe GER. Clinical prospective study. Healthy, client-owned dogs presenting for elective orthopedic surgery. Dogs were sedated with IM methadone (0.2 mg/kg) and medetomidine (5 ug/kg), followed by alfaxalone total intravenous anesthesia. The Digitrapper esophageal dual pH monitoring probe was placed transnasally into the esophagus. Dogs were unsedated during the subsequent recording period. A GER event was defined as esophageal pH less than 4.0. Parameters that described GER were: (1) number of GER events per hour, and (2) cumulative esophageal acid exposure (percentage of recording duration) at each sensor. Upper reference limits were calculated for each parameter. Thirty-five dogs were included (median age 7 years, range 1-12). The median recording duration was 21.1 h (range 13.6-29.3). Productive regurgitation was not noted in any dog. The median number of distal and proximal GER events per hour was 0.3 (range 0-4.3) and 0 (range 0-1), respectively. The median cumulative distal and proximal esophageal acid exposure was 0.2% (range 0.3-9%) and 0% (range 0%-1%), respectively. Upper reference limits for distal and proximal GER per hour was 2.4 and 0.4, respectively, and, for cumulative distal and proximal esophageal acid exposure, 2.3% and 0%, respectively. Dogs undergoing esophageal pH monitoring in a similar hospital setting with parameters above these upper reference limits have excessive GER.

Pediatric Laryngopharyngeal Reflux: An Evidence-Based Review

Pediatric laryngopharyngeal reflux (P-LPR) is associated with the development of common otolaryngological symptoms and findings. In the present study, the findings about epidemiology, clinical presentation, diagnostic and therapeutic outcomes of pediatric population were reviewed. A PubMed, Cochrane Library, and Scopus literature search was conducted about evidence-based findings in epidemiology, clinical presentation, diagnostic and therapeutic outcomes of P-LPR. The prevalence of LPR remains unknown in infant and child populations. The clinical presentation depends on age. Infants with LPR symptoms commonly have both gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux and related digestive, respiratory and ear, nose and throat symptoms. The GERD prevalence appears to decrease over the growth, and the clinical picture is increasingly associated with LPR symptoms and findings without GERD. The prevalence of LPR and proximal acid and nonacid esophageal reflux events may be high in some prevalent otolaryngological conditions (chronic otitis media, laryngolomalacia and apnea). However, the lack of use of hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring (HEMII-pH) limits the establishment of etiological associations. Proton pump inhibitors are less effective in P-LPR patients compared to GERD populations, which may be related to the high prevalence of weakly or nonacid reflux events. Many gray areas persist in P-LPR and should be not resolved without the establishment of diagnostic criteria (guidelines) based on HEMII-pH. The unavailability of HEMII-pH and the poor acid-suppressive therapeutic response are all issues requiring future investigations. Future controlled studies using HEMII-pH and enzyme measurements in ear, nose or throat fluids may clarify the epidemiology of P-LPR according to age and its association with many otolaryngological conditions.

S457 Comparison of the Prevalence of Psychiatric Disorders Among Refractory GERD, Functional Heartburn and Reflux Hypersensitivity

Introduction: Psychiatric disorders were previously reported to be associated with GERD, including anxiety and depression. Functional heartburn (FH) and reflux hypersensitivity (RH) are functional esophageal disorders which involve dysfunction of the gut-brain axis and information about association with neuropsychiatric disorders remains scarce. The aim of our study was to compare the distribution of psychiatric diseases among FH, RH and refractory GERD populations. Methods: Patients were identified through Epic SlicerDicer with selection criteria of GERD, on proton pump inhibitor (PPI) who received esophageal pH monitoring from 2000-2021. FH cohort consisted of patients who had a negative pH test off PPI before the study and lacked endoscopic abnormalities. Similarly, RH cohort was created by selecting patients with a negative pH test off PPI with no endoscopic abnormalities, but with positive symptom association with gastroesophageal reflux events. The refractory GERD group consisted of patients with a positive pH test while on twice daily PPI. Demographic information and psychiatric history including anxiety, depression, schizophrenia, PTSD, and bipolar disorder as well as psychiatric medications were collected. Data were analyzed using ANOVA, Fisher’s exact test, Chi-square test and odds ratio (OR) with a confidence interval of 95%. Results: FH, RH and refractory GERD cohorts consisted of 61, 22 and 38 patients respectively. There was a significant difference in the prevalence of psychiatric conditions overall and anxiety among FH, RH and refractory GERD group (psych conditions: p=0.024; anxiety: p=0.003) (Table). Specifically, both FH and RH had an overall lower prevalence of psychiatric conditions overall when compared with refractory GERD group (FH vs refractory GERD: OR 0.139-0.843, p=0.018; RH vs refractory GERD: OR 0.084-0.796, p=0.016). There was a lower frequency of anxiety and use of benzodiazepines (Benzo) in FH as compared with the refractory GERD group (Anxiety in FH vs refractory GERD: OR 0.098-0.551, p< 0.001; Benzo in FH vs refractory GERD: OR 0.033-0.493, p< 0.001). Conclusion: Our study found a lower frequency of psychiatric disorders and anxiety in the functional esophageal groups as compared with refractory GERD group. However, further studies are warranted to determine the neuropsychiatric differences across different phenotypes of GERD. Table 1. - Comparison of Psychiatric Disorders and Psychotropic Medications Among Refractory GERD, Functional Heartburn and Reflux Hypersensitivity FH (n=61) RH (n=22) Refractory GERD (n=38) p Age 56.0±1.9 53.3±2.7 57.2±2.3 0.583 BMI 29.1±1.0 30.2±1.5 31.7±1.1 0.269 Gender Male 12 (19.7%) 3 (13.6%) 8 (21.1%) 0.770 Female 49 (80.3%) 19 (86.4%) 30 (78.9%) Psych Overall psychiatric conditions 32 (52.5%) 10 (45.5%) 29 (76.3%) 0.024 Anxiety 16 (26.2%) 8 (36.4%) 23 (60.5%) 0.003 Depression 25 (41.0%) 8 (36.4%) 22 (57.9%) 0.166 Schizophrenia 3 (4.9%) 0 1 (2.6%) 0.521 PTSD 3 (4.9%) 2 (36.4%) 4 (10.5%) 0.555 Bipolar 3 (4.9%) 0 2 (5.3%) 0.558 Medications SSRI 13 (21.3%) 4 (18.2%) 14 (36.8%) 0.150 SNRI 3 (4.9%) 2 (9.1%) 6 (15.8%) 0.190 TCA 6 (10.0%) 2 (9.1%) 3 (7.9%) 0.940 Benzodiazepine 3 (4.9%) 0 11 (28.9%) < 0.001

Oral Microbiome Diversity Between Patients With Normal Versus Elevated Salivary Pepsin Levels and Its Implication in Gastroesophageal Reflux Disease

This pilot study aimed to assess oral microbiome diversity between patients with and without elevated salivary pepsin concentrations. Over 9 months, 85 enrolled subjects (73 symptomatic patients; 12 asymptomatic volunteers) provided salivary samples off acid suppression. Subjects with elevated pepsin (≥25 ng/mL) had significantly greater Shannon entropy diversity compared to subjects with normal pepsin (&lt;25 ng/mL) on 16S rRNA sequencing ( P = .015), indicating increased oral microbiome biodiversity in patients with elevated salivary pepsin. Repeated gastro-esophageal reflux events from the stomach to the oral cavity may contribute to this observed change in oral microbiome diversity with potential implications in symptom generation and/or therapy.

Detection of gastroesophageal reflux by multichannel intraluminal impedance technology during mechanical ventilation: the first case series

<h2>Summary</h2><h3>Background & Aims</h3> Gastroesophageal reflux (GER) is a common event among mechanically ventilated and tube-fed critically ill patients and it is associated with an increased risk of ventilator-associated pneumonia. Most of the available tools for the detection of GER are experimental and not available bedside. Intraluminal impedance was suggested as a technique for real-time detection and quantification of GER. This study aimed to evaluate the frequency and duration of GER events in mechanically ventilated and tube-fed patients and to determine their correlation with routine procedures performed during patient care. <h3>Methods</h3> This was a prospective observational study of 20 critically ill patients hospitalized in a university hospital general intensive care unit. We included adult, mechanically ventilated patients receiving continuous enteral feeding by feeding tube (FT). A FT with multichannel intraluminal impedance sensors capable of detecting movement of gastro-esophageal content above the lower esophageal sphincter was used for GER detection. The frequency, duration, and association with routine procedures (position change, suction, and fluid bolus administration) were evaluated. <h3>Results</h3> During the median monitoring time of 2.9 days (IQR 2.8–3) per patient, a median number of 2.7 (IQR 2.1–3.8) GER events were detected every hour. 61% of GERs lasted 10–30 seconds. Position changes, endotracheal suctions, and fluid bolus administrations were associated with a high frequency of GERs. <h3>Conclusions</h3> Multichannel impedance sensors embedded on a FT enable real-time bedside detection of GER. This technology provides an opportunity for the development of new strategies aimed to decrease GER prevalence and prevent aspiration. <h3>Registration</h3> The study was registered at http://www.clinicaltrials.gov (NCT02705781).

Symptoms classically attributed to laryngopharyngeal reflux correlate poorly with pharyngeal reflux events on multichannel intraluminal impedance testing.

Laryngopharyngeal reflux (LPR) is thought to be a common etiology of throat and airway symptoms. Diagnosis of LPR is challenging, given the variable symptomatology and response to therapy. Identifying symptoms that better correlate with LPR may inform management strategies. We aimed to examine the association between patient-reported symptoms and objectively identified LPR on ambulatory reflux monitoring. This was a retrospective cohort study of consecutive adults with suspected LPR undergoing combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing (HEMII-pH) at a tertiary center. All patients completed standardized symptom surveys for presenting symptoms, reflux symptom index (RSI), and voice handicap index (VHI). LPR was defined as >1 full-column pharyngeal reflux event on HEMII-pH over 24hours. Univariate and multivariable analyses were performed. A total of 133 patients were included (mean age = 55.9years, 69.9% female). Of this 83 (62.4%) reported concomitant esophageal symptoms. RSI and VHI did not correlate with proximal esophageal or pharyngeal reflux events (Kendall's tau correlations P > 0.05), although the mean RSI was higher in the LPR group (21.1 ± 18.9 vs. 17.1 ± 8.3, P = 0.044). Cough, but not other laryngeal symptoms, was more common among patients with esophageal symptoms (58% vs. 36%, P = 0.014). Neither laryngeal symptoms nor esophageal symptoms of reflux predicted LPR on univariate or multivariable analyses (all P > 0.05). Neither laryngeal symptoms classically attributed to LPR nor typical esophageal symptoms correlated with pharyngeal reflux events on HEMII-pH. Clinical symptoms alone are not sufficient to make an LPR diagnosis. Broad evaluation for competing differential diagnoses and objective reflux monitoring should be considered in patients with suspected LPR symptoms.

Association Between Antibodies Against Lung Self-Antigens and Gastroesophageal Reflux in Lung Transplant Candidates

Gastroesophageal reflux (GER) and pretransplant antibodies against lung self-antigens (SAbs) collagen-V and/or k-alpha 1 tubulin are both independently associated with allograft dysfunction after lung transplantation (LTx). The role of GER in inducing lung injury and SAbs is unknown. We aimed to study the association between pre-LTx GER and SAbs. After IRB approval, we retrieved SAb assays conducted between 2015 and 2019 and collected 24 hour GER data for these patients. Patients were divided into 2 groups: no reflux (GER-) and pathologic reflux (GER+) to compare the prevalence of SAbs. Multivariate analysis was used to study the association between GER and SAbs in the whole cohort and in restrictive lung disease (RLD) and obstructive lung disease (OLD) subsets. Proximal esophageal reflux (PER) events ≥5 was considered abnormal. Patients (n=134; 73 men) were divided into groups: GER- (54.5%, n=73) and GER+ (45.5%, n=61). The prevalence of GER was higher in the RLD than in the OLD subset (p < 0.001). The overall prevalence of SAbs was 53.7% (n=72), higher in the GER+ than the GER- group (65.6% vs 43.8%, p=0.012), but comparable between RLD and OLD subsets. Overall, SAbs were associated with GER (p=0.012) and abnormal PER (p=0.017). GER and abnormal PER increased the odds of SAbs in the RLD subset (OR [95% CI]: 2.825 [1.033-7.725], p=0.040 and OR [95% CI]: 3.551 [1.271-9.925], p=0.014, respectively) but not in the OLD subset. LTx candidates have a high prevalence of SAbs, which are significantly associated with GER and abnormal PER in patients with RLD.

Symptom Scores and pH-Impedance: Secondary Analysis of a Randomized Controlled Trial in Infants Treated for Gastroesophageal Reflux.

BACKGROUND AND AIMS:To evaluate and compare gastro-esophageal reflux (GER) symptom scores with pH-impedance and test the effects of acid-suppressive medications with or without feeding modifications on pH-impedance in high-risk infants.METHODS:Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) and 24-hour pH-impedance data were analyzed from 94 infants evaluated in a tertiary care setting for GER disease. Longitudinal data from 40 infants that received randomized GER therapy (proton pump inhibitor [PPI] with or without feeding modifications) for 4 weeks followed by 1-week washout were analyzed. Relationships between I-GERQ-R and pH-impedance metrics (acid reflux index, acid and bolus GER events, distal baseline impedance, and symptoms) were examined and effects of treatments compared.RESULTS:(A) Correlations between I-GERQ-R and pH-impedance metrics were weak. (B) I-GERQ-R sensitivity, specificity, and positive predictive values were suboptimal when correlated with pH-impedance metrics. I-GERQ-R negative predictive value (NPV) was high for acid symptom–association probability (NPV = 84%) and distal baseline impedence (NPV = 86%) thresholds. (C) PPI with feeding modifications (vs PPI alone) did not alter pH-impedance metrics or symptom scores (P > .05); however, bolus clearance metrics worsened for both treatment groups (P < .05).CONCLUSIONS:In high-risk infants (1) I-GERQ-R may be a helpful clinical screening tool to exclude acid-GER disease diagnosis and minimize unnecessary acid-suppressive treatment, but further testing is needed for diagnosis. (2) Acid-suppressive therapy with feeding modifications has no effect on symptom scores or pH-impedance metrics. Clearance of refluxate worsened despite PPI therapy, which may signal development of pharyngoesophageal dysmotility and persistence of symptoms. (3) Placebo-controlled trials are needed in high-risk infants with objective pH-impedance criteria to determine efficacy, safety, and underlying mechanisms. Clinicaltrials.gov ID: NCT02486263.

Normative Ambulatory Reflux Monitoring Metrics for Laryngopharyngeal Reflux: A Systematic Review of 720 Healthy Individuals.

To review the normative data for acid, weakly acid, and nonacid proximal esophageal (PRE) and hypopharyngeal reflux (HRE) events in diagnosing laryngopharyngeal reflux (LPR) using ambulatory reflux monitoring. PubMed, Cochrane Library, and Scopus. A literature search was conducted about the normative data for PRE and HRE on multichannel intraluminal impedance-pH monitoring (MII-pH), hypopharyngeal-esophageal MII-pH (HEMII-pH), or oropharyngeal pH monitoring using PICOTS (population, intervention, comparison, outcome, timing, and setting) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Outcomes reviewed included device characteristics, impedance/pH sensor placements, study duration, number/average and percentiles of PRE or HRE occurrence, and the event characteristics (pH, composition, and position). Of 154 identified studies, 18 met criteria for analysis, including 720 healthy individuals. HEMII-pH, MII-pH, and oropharyngeal pH monitoring were used in 7, 6, and 5 studies, respectively. The definition and inclusion/exclusion criteria of healthy individuals varied substantially across studies, with 6 studies considering only digestive symptoms to exclude potential LPR patients. Substantial heterogeneity across studies was noted, including impedance/pH sensor placements/configurations and definitions of composition (liquid, gas, mixed) and type (acid, weakly acid, nonacid) of PRE/HRE. The 95th percentile thresholds were 10 to 73 events for PRE, 0 to 10 events for HRE on HEMII-pH, and 40 to 128 for events with pH <6.0 on oropharyngeal pH monitoring. Most HREs were nonacid and occurred upright. The mean HRE among healthy individuals was 1. The low number of studies and the heterogeneity in inclusion criteria, definitions, and characterization of PRE and HRE limit the establishment of consensual normative criteria for LPR on ambulatory reflux monitoring. Future large multicenter studies are needed.

Expected Values of Esophageal Transit and Gastric Emptying Scintigraphy Post-uncomplicated Sleeve Gastrectomy.

Sleeve gastrectomy (SG) results in significant anatomical and physiological alterations of the esophagus and stomach, including food tolerance. Currently, there is no consensus on the parameters of abnormal esophageal transit and gastric emptying in this population. We describe standardized esophageal transit and gastric emptying protocols, and define expected values following an uncomplicated SG. In 43 asymptomatic post-SG patients with optimal weight loss, a standardized liquid and semi-solid (oatmeal) esophageal transit study, plus a 90-min semi-solid gastric emptying study with dynamic 5-s image acquisition to assess gastroesophageal reflux, was performed. Gastric emptying half-time and retention rate was calculated. Esophageal transit and reflux were graded by visual inspection of images. Thirty-one female and 12 male patients participated: mean age 49.0±10.7 years, pre-operative BMI 47.6±7.0 kg/m2, excess weight loss 58.8±26.0% at median follow-up of 7.4 months. The standardized semi-solid meal and liquid preparations were well tolerated. Delays in esophageal transit of liquid and semi-solid boluses were infrequent (7.0% and 16.3% respectively). Deglutitive reflux of both semi-solids and liquids was common (48.8% and 32.6%). The median semi-solid gastric emptying half-time was 21.0 min. A large proportion of substrate transited into the small bowel on initial image acquisition (median 39.1%). Reflux events during gastric emptying were common (median 5.0 events, 12.7% of image acquisition time). Rapid gastric emptying with asymptomatic deglutitive and post-prandial gastroesophageal reflux events are common following SG. We have defined the expected values of standardized esophageal transit and gastric emptying scintigraphy specifically tailored to SG patients.

Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation

Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes. A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups. DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P= .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure. DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

A Multichannel Intraluminal Impedance Gastroesophageal Reflux Characterization Algorithm Based On Sparse Representation.

Gastroesophageal reflux disease (GERD) is a common digestive disorder with troublesome symptoms that has been affected millions of people worldwide. Multichannel Intraluminal Impedance-pH (MII-pH) monitoring is a recently developed technique, which is currently considered as the gold standard for the diagnosis of GERD. In this paper, we address the problem of characterizing gastroesophageal reflux events in MII signals. A GER detection algorithm has been developed based on the sparse representation of local segments. Two dictionaries are trained using the online dictionary learning approach from the distal impedance data of selected patches of GER and no specific patterns intervals. A classifier is then designed based on the lp-norm of dictionary approximations. Next, a preliminary permutation mask is obtained from the classification results of patches, which is then used in post-processing procedure to investigate the exact timings of GERs at all impedance sites. Our algorithm was tested on 33 MII episodes, resulting a sensitivity of 96.97% and a positive predictive value of 94.12%.

The Role of Combined Multichannel Intraluminal Impedance-pH Monitoring in Infants with Brief, Resolved, Unexplained Events.

PurposeData on the relationship between gastroesophageal reflux (GER) and brief resolved unexplained events (BRUE) in infants is scarce. The aim of this study was to identify the characteristics of combined multichannel intraluminal impedance-pH (MII-pH) monitoring in infants who have experienced BRUE.MethodsWe conducted a prospective study of infants who were hospitalized on account of BRUE and required 24-hour MII-pH monitoring.ResultsTwenty-one infants (mean age, 4.7 months; range, 0.9–8.9 months; male/female, 11/10) participated in this study. BRUE symptoms associated with GER were found in 10 infants (47.6%). Based on the RI on pH-metry alone, only 7 (33.3%) infants were diagnosed with GERD. More than 100 GER episodes detected by MII were found in 10 (47.6%) infants. Nineteen percent of infants were diagnosed with GERD based on both pH and MII.ConclusionBoth acid and non-acid reflux seem to play a significant role in the pathogenesis of GER-related BRUE in infants.

Multichannel Intraluminal Impedance and pH Monitoring: A Step Towards Pediatric Reference Values.

Background/AimsCombined multichannel intraluminal impedance and pH monitoring (MII/pH) is considered the most accurate test to detect gastroesophageal reflux (GER), however lacking reference values. We aim to determine reference values for the pediatric population and to correlate these values with age and postprandial/fasting period.MethodsWe evaluated MII/pH traces from patients (newborns, infants, and children) admitted to 3 Italian hospitals and who underwent MII/pH for suspected GER disease. Patients with MII/pH traces that showed significant symptom-reflux associations and/or a pathological reflux index (> 6% for newborns and infants, > 3% for children) were excluded. Traces were analysed in their entirety, and in the postprandial period (first hour after a meal) and the fasting period (the following hours before the next meal) separately.ResultsA total of 195 patients (46 newborns, 83 infants, and 66 children) were included. Age positively correlated with frequency of acidic GER events (r = 0.37, P < 0.05) and negatively associated with weakly acidic GER events (r = 0.46, P < 0.05).ConclusionsThis study describes the distribution of MII/pH values in a pediatric population with normally acidic GER exposure and no significant association between GER events and symptoms. These MII/pH values may be used as reference values in clinical practice for a corrected GER disease diagnosis in the pediatric population.

Study on laryngopharyngeal and esophageal reflux characteristics using 24-h multichannel intraluminal impedance-pH monitoring in healthy volunteers.

We aimed to analyze the results of 24-h multichannel intraluminal impedance and pH-monitoring (MII-pH) of the laryngopharynx and esophagus in asymptomatic volunteers. Moreover, we also aimed to gain insight into and establish a baseline for laryngopharyngeal reflux in the healthy population by quantitatively and qualitatively comparing the reflux and pH distribution in both the laryngopharynx and the esophagus. Healthy volunteers were recruited and observed; they underwent 24-h ambulatory combined MII-pH monitoring. The proximal sensor (pH1) was positioned approximately 1cm above the upper esophageal sphincter with the aid of a solid-state high-resolution esophageal manometer. Laryngopharyngeal reflux events were detected and characterized by the incidence and property of reflux both in the laryngopharynx and the esophagus. Thirty-eight asymptomatic volunteers who completed all the examinations were included in this study. The median pH detected by the proximal sensor was 6.6 (6.2, 7.0), with an average of 6.58 ± 0.74. A total of 814 laryngopharyngeal reflux events were detected, including 722 (89%) in the upright position and 92 (11%) in the supine position with incidence (0%) in the liquid state, 44 (5%) in the mixture, and 769 (95%) in the gaseous state. Furthermore, 5 incidences (1%) of acid reflux and 809 incidences of non-acid reflux (99%) were noted. A total of 5779 esophageal reflux events were detected, including 5020 (87%) in the upright position, 759 (13%) in the supine position, with 2051 (36%) in the liquid state, 2050 (35%) in the mixed condition, and 1678 (29%) in the gaseous state; adding up to 805 incidences (14%) of acid reflux and 4974 incidences (86%) of non-acid reflux. Non-acid reflux in the upright position is characteristic of laryngopharyngeal reflux. Acid reflux is almost undetectable in healthy subjects. Hence, the diagnostic indicators of gastroesophageal reflux disease are not suitable for laryngopharyngeal reflux disease.

Prolonging gavage feeds for reduction of gastroesophageal reflux in infants.

To determine if prolonging gavage feedings in infants for ≥60 min is associated with decreased gastroesophageal reflux (GER) compared with bolus feeding using multiple-channel intraluminal impedance with pH probe (MII-pH). Retrospective analysis of infants who underwent MII-pH between October 2009 and July 2018 and received gavage feedings. Infants were divided into two groups: bolus (<30 min) or prolonged (≥60 min). Symptoms, number of reflux events and percent time pH < 4 was compared. Fifty-eight infants underwent evaluation. Thirty-one (54%) received bolus gavage feedings and 27 (46%) received prolonged feedings. Groups differed in postmenstrual age. Total reflux episodes were significantly lower with prolonged feeding (median 19 vs. 28 episodes, p = 0.015), with no difference in acid exposure time. There was no significant difference in GER symptoms between the two groups. Prolongation of gavage feedings was associated with decreased total numbers of GER events without reduction in GER symptoms.

Transient Lower Esophageal Sphincter Relaxations and Mechanical Incompetence of the Lower Esophageal Sphincter – Is There a Relationship?

Introduction: The detailed process of a gastroesophageal reflux event is still under controversial discussion. Gastroenterologists have developed and favor the concept of Transient Lower esophageal Sphincter Relaxations (TLESR`s) as the major cause of gastroesophageal reflux episodes. TLESR`s are related with reflux episodes both in healthy individuals and patients with GERD. Another concept around the functional mechanism of the antirefluxbarrier is a more mechanical interpretation of the Lower Esophageal Sphincter (LES), developed by surgeons. The aim of this study is to investigate this relationship between TLESR`s and the mechanical failure of the LES by investigating these criteria in the same individuals. Methods: In a referral center for esophageal and gastric functional disease at the University Hospital in Würzburg, Germany, we investigated healthy volunteers and patients with proven GERD. The assessment of the LES consisted of the overall length, the intraabdominal length, and the end-expiratory pressure of the LES. The manometry was performed in a station-to-station-pull-through technique. The changing LES pressure and the TLESRs were measured with a sleeve catheter according to the protocol published by Dent and Schoeman. The presence of pathologic reflux in patients was evaluated by 24h pH monitoring. Results: In total, 8 healthy volunteers were investigated (median age: 26 years (22-34)). In addition, 21 patients with GERD were evaluated (median age: 49 years (25-68)). The frequency of TLESR´s was quite low in volunteers and patients with 0,4 TLESR`s/h and 0,6 TLESR`s/h respectively. While the frequency of TLESR`s was not different between volunteers and GERD-patients, the percentage of reflux-associated TLESR`s was significantly higher in GERD-patients with mechanically incompetent LES (20,8%), compared to the percentage in GERD-patients with intact LES (6,8%) and also compared to the percentage in healthy volunteers (7,8%) (p<0,001). Conclusion: The present analysis shows a relationship between a mechanically incompetent LES and an increased number of reflux-associated TLESR`s, suggesting that the two mechanisms are not mutually exclusive, but may be instead different measurements of the same condition - a functionally and mechanically defective LES.

Acute administration of fructans increases the number of transient lower esophageal sphincter relaxations in healthy volunteers.

Dietary measures are often advised to patients with gastro-esophageal reflux disease (GERD). Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) induce lower gastrointestinal (GI) symptoms. However, their effects on esophageal motility, including transient lower esophageal sphincter relaxations (TLESRs), reflux events and GERD symptoms are unknown. We investigated the effect of acute administration oftwo FODMAPs, fructose, and fructans, on the number of TLESRs, reflux episodes and symptom perception in healthy volunteers (HVs). After an overnight fast, 20 HVs (10 males; 32.6±2.8years) underwent a high-resolution impedance manometry. The number of TLESRs and reflux episodes was quantified during five hours after consumption of a high-caloric meal (740kcal) enriched with 40g of either fructose, fructans or glucose (as placebo). Results were analyzed using mixed models. There was a trend for a change in the number of TLESRs between the three conditions (P=.06). Post hoc analysis revealed a trend toward a higher number of TLESRs in the fructan condition compared with placebo (Pcorr =.06). Acute administration of fructose did not influence the number of TLESRs. The total number of reflux events was not affected by either FODMAP condition. Lower esophageal sphincter (LES) pressures dropped significantly in the first postprandial hour to recover slowly back to baseline values (P<.0001), without any difference in LES pressure between the three conditions. Ingestion of fructans increased the number of TLESRs slightly compared with placebo. The effect of FODMAPs such as fructans or a low FODMAP diet on reflux parameters in GERD patients remains to be investigated.

420 Assessing the Prevalence of Gastroesophageal Reflux in Gastroparesis: Putting the G Back in GERD

INTRODUCTION: Patients with gastroparesis experience a wide range of symptoms from early satiety to frequent emesis and severe abdominal pain. However, few studies have evaluated concomitant underlying esophageal pathology or frequency of gastroesophageal reflux episodes in patients diagnosed with gastroparesis. Prolonged gastric emptying may lead to increased intra-gastric pressure and volume of gastric contents that may result in increased frequency of distal esophageal reflux events. The aim of this study was to assess for significant differences in total duration of distal esophagus acid exposure and number of gastroesophageal reflux events as detected by impedance pH testing between gastroparesis and control cohorts. METHODS: A retrospective analysis of 84 patient charts who underwent both 4-hour gastric emptying studies and 24-hour ambulatory pH testing was performed. Patients with gastroparesis, as documented by abnormal 4-hour gastric emptying studies, were compared with age and gender matched controls. Patients taking PPI during testing were excluded from the study. Percent of total distal esophageal time pH &lt; 4 (nl &lt; 4%) and impedance values (nl&lt; 53) were compared between the gastroparesis and control groups. Continuous variables were analyzed using independent 2-tailed t-test, while categorical values were evaluated using a chi squared analysis. RESULTS: Forty-two gastroparesis patients (9 men and 33 women, median age 46 years old, range 19-81 years old) underwent 24-hour ambulatory pH monitoring while off of PPI. When comparing total mean impedance events during pH testing, the gastroparesis cohort experienced significantly more episodes of distal esophageal reflux events, 61.27 ± 11.34 vs 45.81 ± 7.72 (P = 0.028), respectively. Mean percent total distal time for esophageal pH &lt; 4.0 was higher for the gastroparesis group when compared to controls, 4.79 ± 1.48% vs 3.31 ± 1.15% (P = 0.125), respectively. CONCLUSION: This pilot study demonstrates that patients meeting criteria for gastroparesis by gastric emptying study have significantly higher number of reflux episodes than those with normal gastric emptying. Trends toward a higher percentage of total distal esophageal acidity exposure time and a higher proportion of the gastroparesis group meeting diagnostic criteria for GERD were also seen. In the future, expanding sample sizes to better investigate these preliminary trends will be beneficial to better understand the association of GERD and gastroparesis.