Abnormal Reflux Research Articles

Model to Select On-Therapy vs Off-Therapy Tests for Patients With Refractory Esophageal or Extraesophageal Symptoms

It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux. We performed a prospective study of 471 adult patients with refractory heartburn (n= 214) or suspected EER symptoms (n= 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom). Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P= .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m2. In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort. We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed byproton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients.

Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial

Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to determine whether treatment of abnormal acid GER with laparoscopic anti-reflux surgery reduces the rate of disease progression. The WRAP-IPF trial was a randomised controlled trial of laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER recruited from six academic centres in the USA. We enrolled patients with IPF, abnormal acid GER (DeMeester score of ≥14·7; measured by 24-h pH monitoring) and preserved forced vital capacity (FVC). We excluded patients with a FVC below 50% predicted, a FEV1/FVC ratio of less than 0·65, a history of acute respiratory illness in the past 12 weeks, a body-mass index greater than 35, and known severe pulmonary hypertension. Concomitant therapy with nintedanib and pirfenidone was allowed. The primary endpoint was change in FVC from randomisation to week 48, in the intention-to-treat population with mixed-effects models for repeated measures. This trial is registered with ClinicalTrials.gov, number NCT01982968. Between June 1, 2014, and Sept 30, 2016, we screened 72 patients and randomly assigned 58 patients to receive surgery (n=29) or no surgery (n=29). 27 patients in the surgery group and 20 patients in the no surgery group had an FVC measurement at 48 weeks (p=0·041). Intention-to-treat analysis adjusted for baseline anti-fibrotic use demonstrated the adjusted rate of change in FVC over 48 weeks was -0·05 L (95% CI -0·15 to 0·05) in the surgery group and -0·13 L (-0·23 to -0·02) in the non-surgery group (p=0·28). Acute exacerbation, respiratory-related hospitalisation, and death was less common in the surgery group without statistical significance. Dysphagia (eight [29%] of 28) and abdominal distention (four [14%] of 28) were the most common adverse events after surgery. There was one death in the surgery group and four deaths in the non-surgery group. Laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER is safe and well tolerated. A larger, well powered, randomised controlled study of anti-reflux surgery is needed in this population. US National Institutes of Health National Heart, Lung and Blood Institute.

Pathophysiology of gastroesophageal reflux disease: how an antireflux procedure works (or does not work).

The pathophysiology of gastroesophageal reflux disease is complex and linked to an intricate valve mechanism at the level of the esophagogastric junction that must counteract a trans-diaphragmatic pressure gradient, which is constantly forcing gastric contents upwards. Surgical antireflux therapy is usually aimed towards reinforcement of this valve mechanism. The valve mechanism is made up by the intra-abdominal length of the esophagus; the diaphragmatic sphincter, the angle of His, and the lower esophageal sphincter: all these elements must be restored with an antireflux procedure. Hiatal approximation and fundoplication determine excellent outcomes in patients in whom the abnormal reflux is mostly due to the valve mechanism. In patients with altered intra-abdominal pressure due to obesity, a bariatric procedure such as a Roux-en-Y gastric bypass is probably more appropriate. For patients with an altered intra-thoracic pressure such as in idiopathic pulmonary fibrosis, a fundoplication has been shown to be beneficial in resolving symptoms and avoiding progression of the diseases.

Nonerosive reflux disease: clinical concepts.

Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD.

Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel.

The aim of this study was to assess expert gastroenterologists' opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: H2RA for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association. For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies are preferred for all other scenarios.

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease

BackgroundGastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children. AimsTo evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease. MethodsPatients were classified by age groups (A–C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages. ResultsThe study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy. ConclusionsWe confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy.

Laparoscopic Heller Myotomy and Fundoplication: What Is the Evidence?

There is no agreement about the best type of fundoplication to add in patients undergoing laparoscopic Heller myotomy (LHM) for achalasia to reduce the risk of postoperative gastroesophageal reflux. This article reviews the current evidence about the outcomes in achalasia patients undergoing LHM with a partial anterior, a partial posterior, or a total fundoplication. We performed a review of the literature in PubMed/Medline electronic databases, which was evaluated according to the GRADE system. The results of the published randomized controlled trials show with a high level of evidence that the addition of a fundoplication reduces the risk of postoperative abnormal reflux, without impairing the food emptying of the esophagus. LHM with partial fundoplication is considered in most centers worldwide the standard of care for the treatment of patients with achalasia. The current evidence fails to show any significant difference between partial anterior and posterior fundoplication. In the absence of further large randomized controlled trial, the decision of performing an anterior or a posterior wrap is based on the surgeon's experience and preference. The addition of a partial fundoplication to LHM leads to a significantly lower rate of postoperative pathological reflux without impairing the esophageal emptying.

SWALLOWING IN PATIENTS WITH LARYNGITIS.

Dysphagia is described as a complaint in 32% of patients with laryngitis. The objective of this investigation was to evaluate oral and pharyngeal transit of patients with laryngitis, with the hypothesis that alteration in oral-pharyngeal bolus transit may be involved with dysphagia. Videofluoroscopic evaluation of the swallowing of liquid, paste and solid boluses was performed in 21 patients with laryngitis, 10 of them with dysphagia, and 21 normal volunteers of the same age and sex. Two swallows of 5 mL liquid bolus, two swallows of 5 mL paste bolus and two swallows of a solid bolus were evaluated in a random sequence. The liquid bolus was 100% liquid barium sulfate and the paste bolus was prepared with 50 mL of liquid barium and 4 g of food thickener (starch and maltodextrin). The solid bolus was a soft 2.2 g cookie coated with liquid barium. Durations of oral preparation, oral transit, pharyngeal transit, pharyngeal clearance, upper esophageal sphincter opening, hyoid movement and oral-pharyngeal transit were measured. All patients performed 24-hour distal esophageal pH evaluation previous to videofluoroscopy. The evaluation of 24-hour distal esophageal pH showed abnormal gastroesophageal acid reflux in 10 patients. Patients showed longer oral preparation for paste bolus and a faster oral transit time for solid bolus than normal volunteers. Patients with laryngitis and dysphagia had longer preparation for paste and solid boluses, and a faster oral transit time with liquid, paste and solid boluses. A longer oral preparation for paste and solid boluses and a faster transit through the mouth are associated with dysphagia in patients with laryngitis.

Extraesophageal Symptoms and Diseases Attributed to GERD: Where is the Pendulum Swinging Now?

The purpose of this review is to outline the recent developments in the field of extraesophageal reflux disease and provide clinically relevant recommendations. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: Best Practice Advice 1: The role of a gastroenterologist in patients referred for evaluation of suspected extra esophageal symptom is to assess for gastroesophageal etiologies that could contribute to the presenting symptoms. Best Practice Advice 2: Non-GI evaluations by ENT, pulmonary and/or allergy are essential and often should be performed initially in mostpatients as the cause of the extraesophageal symptom is commonly multifactorial or not esophageal inorigin. Best Practice Advice 3: Empiric therapy with aggressive acid suppression for 6-8 weeks with special focus on response of the extraesophageal symptoms can help in assessing association between reflux and extraesophageal symptoms. Best Practice Advice 4: No single testing methodology exists to definitively identify reflux as the etiology for the suspected extra esophageal symptoms. Best Practice Advice 5: Constellation of patient presentation, diagnostic test results and response to therapy should be employed in the determination of reflux as a possible etiology in extra esophageal symptoms. Best Practice Advice 6: Testing may need to be off or on proton pump inhibitor (PPI) therapy depending on patients' presenting demographics and symptoms in assessing the likelihood of abnormal gastroesophageal reflux. A. On therapy testing may be considered in those with high probability of baseline reflux (those with previous esophagitis, Barrett's esophagus or abnormal pH). B. Off therapy testing may be considered in those with low probability of baseline reflux with the goal of identifying moderate to severe reflux at baseline. Best Practice Advice 7: Lack of response to aggressive acid suppressive therapy combined with normal pH testing off therapy or impedance-pH testing on therapy significantly reduces the likelihood that reflux is a contributing etiology in presenting extraesophageal symptoms. Best Practice Advice 8: Surgical fundoplication is discouraged in those with extra esophageal reflux symptoms unresponsive to aggressive PPI therapy. Best Practice Advice 9: Fundoplication should only be considered in those with a mechanical defect (e.g., hiatal hernia), moderate to severe reflux at baseline off PPI therapy who have continued reflux despite PPI therapy and have failed more conservative non-GI treatments.

Functional performance in late-onset GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), longitudinal data over 3 consecutive years

Anatomically, the normal state in the human adult is an esophagus that is entirely tubular and has a sharp transition to the saccular stomach where it forms an acute angle of His. Histologically, the normal esophagus is lined entirely by stratified squamous epithelium, transitioning at the gastroesophageal junction to gastric oxyntic epithelium, which lines the entire proximal stomach. Cardiac epithelium is normally absent. Its presence indicates the abnormal state of the dilated distal esophagus that results from damage to the abdominal segment of the lower esophageal sphincter. It is the early stage of gastroesophageal reflux disease (GERD) that is presently ignored and mistaken as normal proximal stomach. This normal state is not recognized at present time by the myth that 1–4 mm of cardiac epithelium normally exists between the distal end of the squamous epithelium and the proximal limit of gastric oxyntic epithelium. Evidence that eradicates this myth includes the facts: (1) The cardiac epithelium is absent in some people. (2) The presence of cardiac epithelium in the dilated distal esophagus is associated with the presence of submucosal esophageal glands. (3) Its extent varies from 0 to <15 mm in persons without GERD and increases up to 30 mm in patients with GERD. (4) The presence of any cardiac epithelium is associated with abnormal acid exposure, reflux esophagitis, and manometric abnormalities in the lower esophageal sphincter. (5) Cardiac epithelium extends into the thoracic esophagus as visible columnar-lined esophagus (CLE) in patients with severe GERD associated with severe lower esophageal sphincter damage. (6) The morphologic, immunohistochemical, and molecular features of cardiac epithelium in the dilated distal esophagus and visible CLE are identical and different than those of distal gastric epithelium. Eradication of the myth that cardiac epithelium is normally absent is essential to the understanding of the pathologic changes associated with the earliest stage of GERD. Existence of the myth at present prevents this understanding.

Esophagogastric junction and esophageal body contraction metrics on high-resolution manometry predict esophageal acid burden.

Distal contractile integral (DCI) and esophagogastric junction contractile integral (EGJ-CI) are high-resolution manometry (HRM) software metrics assessing esophageal motor function in gastroesophageal reflux disease (GERD). Patients undergoing HRM and ambulatory pH monitoring off antisecretory therapy prospectively completed symptom questionnaires assessing symptom burden and a global symptom score (GSS) at baseline and after GERD therapy. DCI<450mmHg/cm/s in ≥5 swallows diagnosed ineffective esophageal motility (IEM); proportions of failed (DCI<100mmHg/cm/s) and weak (DCI 100-450mmHg/cm/s) sequences were separately assessed. EGJ-CI assessed vigor of the EGJ barrier. Univariate and multivariate analyses addressed performance of esophageal body and EGJ metrics in predicting abnormal esophageal reflux burden, and symptom outcome from antireflux therapy. Of 188 patients (55.2±0.9year, 64% F), 42.6% had low EGJ-CI, and 25.0% had IEM. While low EGJ-CI was associated with abnormal reflux burden (P=0.003), IEM alone was not (P=0.2). Increasing proportions of failed swallows predicted abnormal AET better than the current IEM definition. Combined low EGJ-CI and IEM segregated abnormal total and supine acid burden compared to patients with normal EGJ-CI and no IEM (P≤0.007 for each comparison). Medical therapy and surgical antireflux therapy were similarly effective in improving symptom burden; surgery resulted in better outcomes with low EGJ-CI (P≤0.04), especially with intact esophageal body motor function (P=0.02). While abnormal EGJ and esophageal body metrics are collectively associated with elevated esophageal reflux burden, increasing proportions of failed swallows are better predictors of reflux burden and outcome compared to the current IEM definition.

The overlap of gastroesophageal reflux disease and functional constipation in children: the efficacy of constipation treatment.

This study was designed to investigate the frequency of gastroesophageal reflux disease (GERD) in children with functional constipation (FC). It was structured to assess the improvement level in reflux symptoms by measuring the acid reflux in these patients after they had received FC treatment. Ninety-four children who suffered from constipation were evaluated prospectively. Data forms were completed to assess the GERD symptoms in all the cases. Twenty-four-hour pH meter monitoring was performed in 55 of the patients with GERD symptoms. The cases with abnormal acid reflux were treated by conventional therapy for FC. These cases were re-evaluated for GERD symptoms and weekly defecation frequency, and 24-h pH meter monitoring was performed at the end of a 3-month period. An abnormal level of acid reflux was determined in 23 of the 55 cases. After the constipation treatment, a significant improvement was achieved in the acid reflux index and GERD symptoms, whereas the weekly defecation frequency increased. GERD is a frequent problem in children with FC. Treatment of the constipation can improve the reflux symptoms and abnormal acid reflux in these cases. Physicians should bear in mind the co-occurrence of these two prevalent problems for better disease management.

Facts and Fantasies on Extraesophageal Reflux: A Gastroenterologist Perspective.

Gastroesophageal reflux disease encompasses a wide spectrum of disorders related to the reflux of gastric contents into the esophagus. Extraesophageal reflux (EER) may be suspected in patients with unexplained chronic cough, pharyngolaryngeal symptoms, and asthma. For physicians, suspected EER is challenging as there is currently no tool that can reliably make a definitive diagnosis. Endoscopic signs are not specific, pharyngeal and proximal reflux monitoring are not reliable, and if distal pH or pH-impedance monitoring can identify patients with abnormal reflux, they cannot predict the response to therapy. Controlled randomized trials have failed to reliably demonstrate any benefit of high-dose proton-pump inhibitors over placebo in patients with laryngeal symptoms, chronic cough, and asthma. Overall, the role of gastroesophageal reflux has been largely overestimated in patients with suspected EER. Especially when proton-pump inhibitors failed to improve symptoms, other diagnosis should be considered, such as functional laryngeal disorders which are probably much more prevalent in these patients than pathologic gastroesophageal reflux.

Dissociated recovery between dementia and parkinsonism by transvenous embolization of recurrent dural arteriovenous fistula

AbstractDementia and parkinsonism are rarely observed in dural arteriovenous fistula. Here, we report a case of a 63‐year‐old man with recurrent dural arteriovenous fistula, who developed progressive dementia and parkinsonism as a result of a dural arteriovenous fistula at the torcular herophili. A sinus thrombosis induced the abnormal cortical venous reflux from the isolated straight sinus, resulting in the deep venous congestion of the thalamus and basal ganglia, which led to dementia and parkinsonism. However, the third endovascular embolization ameliorated memory disturbance and apathy with a slight improvement of parkinsonism. Although recoveries from dural arteriovenous fistula‐associated neurological deficits are variable depending on the severity, duration and, furthermore, selective vulnerability of the responsible ischemic lesions, early treatment should be essential for better recovery.

Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe

Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.

Proton pump inhibitor-responsive esophageal eosinophilia: still a valid diagnosis?

To update rapidly evolving concepts regarding the controversial entity of 'proton pump inhibitor (PPI)-responsive esophageal eosinophilia,' referring to patients with clinical, endoscopic and histologic features of eosinophilic esophagitis (EoE) who achieve remission on PPI therapy. Up to half of pediatric and adult patients with typical EoE symptoms and histology achieve clinico-pathologic remission on PPI therapy, irrespective of whether esophageal pH monitoring demonstrates abnormal acid reflux. In patients with clinical and histologic features of EoE, genotypic and phenotypic features of PPI responders and nonresponders are virtually indistinguishable, and different from those of patients with gastroesophageal reflux disease. In PPI responders, PPIs effects on esophageal Th2 inflammation and gene expression are similar to those of topical steroids in PPI nonresponders. These therapies, along with diets, recently have been shown to be potentially interchangeable in two small series. Proton pump inhibitor-responsive esophageal eosinophilia is an inappropriate disease descriptor, arbitrarily based on a response to a single drug, and should be abandoned. Patients who have esophageal eosinophilia and esophageal symptoms that resolve with PPI therapy have phenotypic, molecular, mechanistic, and therapeutic features indistinguishable from similar patients who do not respond to PPIs. These patients with PPI responsiveness should be considered within the spectrum of EoE.

Impaired Esophageal Motility and Clearance Post-Lung Transplant: Risk For Chronic Allograft Failure

Objectives:Gastroesophageal reflux is common in patients post-lung transplantation (LTx) and thus considered a risk factor for aspiration and consequently allograft rejection and the development of chronic allograft failure. However, evidence supporting this remains unclear and often contradictory. Our aim was to examine the role played by esophageal motility on gastroesophageal reflux exposure, along with its clearance and that of boluses swallowed, and the relationship to development of obstructive chronic lung allograft dysfunction (o-CLAD).Methods:Patients post-LTx (n=50, 26 female; mean age 55 years (range, 20–73 years)) completed high-resolution impedance manometry and 24-h pH/impedance. Esophageal motility abnormalities were classified based upon the Chicago Classification version 3.0.Results:Esophagogastric junction outflow obstruction alone (EGJOOa) (P=0.01), incomplete bolus transit (IBT) (P=0.006) and proximal reflux (P=0.042) increased the risk for o-CLAD. Patients with EGJOOa were most likely to present with o-CLAD (77%); despite being less likely to exhibit abnormal numbers of reflux events (10%) compared with those with normal motility (o-CLAD: 29%, P<0.05; abnormal reflux events: 64%, P<0.05). Patients with EGJOOa had lower total reflux bolus exposure time than those with normal motility (0.6 vs. 1.5% P<0.05). In addition, poor esophageal clearance documented by abnormal post-reflux swallow-induced peristaltic wave index associated with o-CLAD; inversely correlating with the proportion of reflux events reaching the proximal esophagus (r=−0.251; P=0.052).Conclusions:These observations support esophageal dysmotility, especially EGJOOa, and impaired clearance of swallowed bolus or refluxed contents, more so than just the presence of gastroesophageal reflux alone, as important risk factors in the development of o-CLAD.

Sa1173 - Female Gender is the Only Significant Clinical Predictor for Abnormal Pharyngeal Reflux on Impedance-pH Monitoring in Patients with Suspected Laryngopharyngeal Reflux Symptoms

Sa1173 - Female Gender is the Only Significant Clinical Predictor for Abnormal Pharyngeal Reflux on Impedance-pH Monitoring in Patients with Suspected Laryngopharyngeal Reflux Symptoms

Manometric Subtypes of Ineffective Esophageal Motility.

Objectives:Ineffective esophageal motility (IEM) is characterized by well-defined manometric criteria. However, much variation exists within the diagnosis: Some patients exhibit exactly the required five weak swallows to make the diagnosis. Others show consistently ineffective swallows with total absence of any normal swallow. “We hypothesize” there are two different manometric subtypes of IEM; IEM Alternans (IEM-A) and IEM Persistens (IEM-P).Methods:A total of 231 IEM patients were identified by high-resolution manometry (HRM). IEM defined by distal contractile integral (DCI) <450 mm Hg/s/cm in ≥50% of test swallows. Abnormal reflux study was defined by excess total number of reflux episodes, abnormal esophageal acid exposure, or positive symptom association.Results:A total of 195 (84%) patients had IEM-A and 36 (16%) had IEM-P. A striking gender difference with 34% of IEM-A being males compared to 53% of IEM-P. (P=0.03). Mean age of IEM-P (59.6 years+/−13.1) was greater than IEM-A (55.5 years+/−13.6) (P=0.04). Mean lower esophageal sphincter (LES) resting pressure was significantly lower in IEM-P (20.8 mm Hg+/−1.4) than IEM-A (29 mm Hg+/−1.2) (P=0.002). There was no difference in LES-integrated relaxation pressure (IRP), bolus transit, or manometric presence of hiatal hernia between the two groups. Out of 146, 89 (61%) patients had abnormal reflux study. Esophageal acid exposure in upright position was significantly higher in IEM-P than IEM-A (3.5 vs. 1.7%, P=0.04). Poor gastric acid control on proton pump inhibitor (PPI) was more prevalent among IEM-P patients (58%) than IEM-A (27%) (P=0.007). In subgroup analysis of 41 IEM patients with dysphagia, DCI for liquid swallows was significantly lower in IEM-P (111+/−142 mm Hg/s/cm) compared to IEM-A (421+/−502 mm Hg/s/cm) (P=0.04), lower mean LES resting pressure in IEM-P (16.6+/−9 mm Hg) than IEM-A (31.7+/−18 mm Hg) (P=0.01).Conclusions:There are two distinct manometric IEM subtypes; IEM-P with an older male predominance, more advanced reflux disease, weaker LES, and worse response to PPI; likely a more advanced manifestation than IEM-A. However, the question if there are different etiologies underlying the two subtypes remains to be answered.

Impact of gastroesophageal reflux and delayed gastric emptying on pediatric lung transplant outcomes

Gastroesophageal reflux disease is thought to predispose to adverse lung allograft outcomes. However, little is known about the burden of gastroesophageal reflux (GER) and gastroparesis in pediatric patients. In this study we describe the burden of reflux and gastroparesis in children undergoing lung transplant, and evaluates their impact on allograft survival and rejection incidence. This study is a retrospective analysis of pediatric lung transplant recipients who had combined pH and multichannel intraluminal impedance testing (pH-MII) and gastric-emptying scans (GES). Hazard ratios with 95% confidence intervals (CIs) estimated from Cox proportional hazard models were used to examine the associations between reflux parameters and adverse allograft outcomes. Covariates considered in the multivariate analysis included abnormal pH-MII testing, abnormal GES and Nissen fundoplication status. Kaplan-Meier curves were created, with log-rank testing employed to assess differences between groups. Thirty lung transplant recipients, aged 1 to 21 years, were identified. Eight of 30 patients (27%) had abnormal reflux by impedance, and 12 (40%) had abnormal pH-metry. Of 19 patients tested, 5 (26.3%) had evidence of gastric dysmotility; however, the severity of GER did not trend with delays in gastric emptying. Neither reflux burden by pH-MII testing nor fundoplication status impacted survival or rejection. However, delayed gastric emptying appeared significantly linked to the development of chronic lung allograft dysfunction, independent of GER. In children, reflux burden and fundoplication status do not impact lung transplant outcomes, but gastric dysmotility may be linked to allograft dysfunction in children.