Erosive Esophagitis Patients Research Articles

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis.

Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. A systematic review and network meta-analysis. Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. The study protocol was registered with INPLASY (registration number INPLASY2023120053).

Value of 96-hour ambulatory esophageal pH monitoring in the assessment of patients with refractory acid reflux symptoms and their response to anti-reflux diet.

Ambulatory esophageal pH monitoring is a diagnostic tool in patients with heartburn and regurgitation. The aim of this study is to evaluate 96-hour esophageal pH monitoring in patients with gastroesophageal reflux disease (GERD), at baseline and under diet that impedes GER. We hypothesized that diet would potentially reduce pathologic acid exposure time (AET). Retrospective series of 88 patients with GERD undergoing wireless 96-hour pH monitoring. Two-day (48hours) tandem periods, one on liberal, followed by another on restricted diet assessed esophageal AET. Primary end point was >30% reduction in AET while on anti-GER diet. Of the 88 patients, 16 were excluded because of probe migration. Endoscopy and biopsies assessed erosive esophagitis (EE) and Barrett's esophagus (BE), or normal esophagus. Abnormal AET (% pH < 4.0 ≥ 6) further defined nonerosive reflux disease (NERD), whereas normal AET (% pH < 4.0 < 6) with normal endoscopy defined patients as functional heartburn (FH). There were 6 patients with EE (n = 5) and BE (n = 1), 23 with NERD and 43 with FH. Anti-GER diet led to >30% reduction in AET in EE and NERD patients, but not in those with FH. Most patients (n = 43/72; 60%) had FH and could have avoided acid suppression. Furthermore, (14/23; 61%) of patients with NERD completely normalized AET with diet, potentially negating acid suppression. Ninety-six-hour esophageal pH distinguishes GERD patients from those with FH. Fifty percent of EE/BE patients and 61% of those with NERD completely normalize AET with diet. If pathologic AET occurs despite diet, acid suppression is indicated.

Expression of VEGF, EGF, and Their Receptors in Squamous Esophageal Mucosa, with Correlations to Histological Findings and Endoscopic Minimal Changes, in Patients with Different GERD Phenotypes.

Background: Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett’s esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients. Methods: The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR). Results: The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs. Conclusions: Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.

The role of vonoprazan in patients with erosive esophagitis.

Acid suppression is the primary therapy for erosive esophagitis (EE). Although proton pump inhibitors (PPIs) are considered as the first-line medication for EE, 10–20% of patients with Los Angeles C and D grade EE do not gain complete mucosal healing and symptom control despite 8-week double-dose PPI treatment. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which blocks the H+, K+-adenosine triphosphatase enzymes in a K+-competitive and reversible manner. Vonoprazan exhibits different pharmacological and pharmacokinetic profiles from conventional PPIs, and has a rapid, potent and sustained acid inhibitory effect. In this review, we summarized and discussed current evidence regarding the role of vonoprazan in terms of mucosal healing, maintaining remission and symptom relief for the management of EE, including the initial and maintenance treatment of EE, as well as for PPI-resistant EE patients. Safety concerns and cost-effectiveness analysis of vonoprazan were also mentioned in the article. As a potent and well-tolerated acid blocker, vonoprazan has the potential to become a novel option for the management of EE.

PGI20 Diagnosis and Treatment Patterns of Gastroesophageal Reflux Disease in China: A Retrospective Real-World Study

This study sought to assess real-world diagnostic practices, treatment patterns, treatment effectiveness, and cost of gastroesophageal reflux disease (GERD) in China, which are currently limited. Retrospective data of patients with a GERD diagnosis were pooled from Electronic Medical Records across 11 hospitals (10 provinces) in China (January 2015 to December 2017). Primary outcomes included GERD patient characteristics, trends in hospital department visits, symptom types, and treatment patterns. Secondary outcomes included the proportion and grade of erosive esophagitis (EE), mucosal healing rate, healthcare resource utilization and associated costs. Descriptive analyses and Wilcoxon rank-sum test are performed. 71,904 patients (48.1% male; mean (SD) age, 49.28 years) with a GERD diagnosis were identified, of which 65.6% were diagnosed and treated in a gastrointestinal department. GERD subtypes identified were non-erosive reflux disease (NERD;82.8%), EE (15.5%), and Barrett’s esophagitis (1.7%). Los Angeles A-B comprised the majority of EE (93.8%, n=1396/1488). Typical, atypical, and extraesophageal symptoms occurred in 62.7%, 48.3% and 12.1% of GERD patients, respectively. Approximately, 16.4% of GERD patients underwent endoscopic examination. Proton pump inhibitors (PPIs) were the most prescribed medication for GERD (95.6%), followed by gastroprokinetic agents (57.3%). Furthermore, 75.8% of PPIs were prescribed in combination regimens (74.1% with gastroprokinetic agents, 6.5% with mucosal protectants and 2.9% with H2 antagonists). The EE mucosal healing rate after standard treatment regimens was 50% in EE patients who has two endoscopic results within 12 weeks. Overall, median cost per outpatient visit was significantly higher for gastrointestinal vs. non-gastrointestinal departments (¥424.6 vs. ¥387.82; p<0.01). NERD was the most common subtype in GERD patients in China. Low endoscopy (to diagnose GERD) and mucosal healing rates in EE were observed. PPI combination treatment was the most prescribed regimen, suggesting inadequate symptom control with PPI monotherapy.

Novel physiologic nomogram discriminates symptom outcome in patients with erosive esophagitis.

Most of patients with erosive esophagitis (EE) are of LA grade A&B with low reflux burden, therefore require further esophageal function tests (EFTs). One-third of them respond poorly to pump proton inhibitor (PPI) treatment. The aim was to establish and validate a physiologic nomogram to discriminate symptom outcome to PPI treatment in patients with EE. A total of 79 EE patients with heartburn who underwent EFTs and received PPI therapy were randomly assigned into a training set (n = 55) and a validation set (n = 24). Clinical data including physiologic parameters from EFTs were collected. Significant factors for the positive symptomatic outcome were identified using logistic regression analysis. Physiologic signature was developed using the least absolute shrinkage and selection operator algorithm. The nomogram was established by combining significant factors and physiologic signature, and its performance was evaluated and validated in the training and validation set. The clinical value of the nomogram was measured by decision curve analysis. Significant factors for positive symptomatic response to PPI treatment were identified as follows: acid exposure time, total number of reflux episodes, and two novel metrics including mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index. The nomogram which incorporated both significant factors and physiologic signature demonstrated good performance in the training and validation sets [C-index: 0.938 (95% CI 0.882-0.995); 0.839 (95% CI 0.678-0.995), respectively]. Decision curves showed significant clinical usefulness. The first physiologic nomogram was developed to discriminate the individualized response to PPI therapy among EE patients.

Polysaccharide from Gracilaria caudata protects the human esophageal mucosal barrier: A differential topical effect and structural dependence

This study aimed to evaluate the in vitro protective effect of topical treatment with a native sulfated polysaccharide of G. caudata (SP-Gc), hydrolyzed (H-SP-Gc), or desulfated (D-SP-Gc) polysaccharide of Gracilaria caudata in esophageal biopsies obtained from GERD patients. Biopsies were obtained from nonerosive reflux disease (NERD) patients and from erosive esophagitis patients. Then, the biopsies were mounted in an Ussing chamber to measure the basal transepithelial electrical resistance (TEER). The effect of mucosal exposure to an acid solution on TEER was analyzed with or without different concentrations (1, 0.3 or 1%) of SP-Gc, H-SP-Gc, or D-SP-Gc, precoated on the mucosa. Basal esophageal mucosal electrical resistance was significantly lower in erosive esophagitis than from NERD. Mucosal samples precoated with native SP-Gc (1%) significantly prevented TEER drop induced by an acidic solution in NERD, but this effect was not observed in erosive esophagitis. Topical application of D-SP-Gc showed no difference compared to native SP-Gc. However, when treated with chemically-modified SP-Gc, the protective effect observed with native SP-Gc was lost. The present study indicated that SP-Gc protects the human esophageal mucosal barrier in NERD patients. This effect is dependent on the structure but is independent of the presence of sulfate.

Efficacy of Alginate-Antacid Medication in the Treatment of Patients with Gastroesophageal Reflux Disease

Efficacy of Alginate-Antacid Medication in the Treatment of Patients with Gastroesophageal Reflux Disease

Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment.

Background/AimsEsophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment.MethodsNinety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2–4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients.ResultsThe intercellular spaces were dilated in both EE and NERD patients (P < 0.05). The value 0.73 μm could be used as the cut-off DIS value to distinguish patients from controls (area under the curve [AUC] = 0.849, P < 0.01). One thousand seven hundred sixty-four ohms could be used as the cut-off impedance values to distinguish patients from controls (AUC = 0.794, P < 0.01). The baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time (r = −0.527, P < 0.05). There was a weak correlation between DIS and baseline impedance (r = −0.230, P < 0.05). “Baseline impedance > 1764 Ω” was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4–58.9; P < 0.01).ConclusionsThe DIS and decreased baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.

Abdominal Visceral to Subcutaneous Adipose Tissue Ratio Is Associated with Increased Risk of Erosive Esophagitis

BackgroundTo investigate the association between abdominal fat distribution represented by the visceral fat area (VFA) to subcutaneous fat area (SFA) ratio, and erosive esophagitis (EE).MethodsSeven hundred and twenty-eight participants aged >40 years underwent physical examination, blood tests, esophagogastroduodenoscopy, and abdominal computer tomography at Chung-Ang University Hospital from 2007 to 2012.ResultsOf 728 subjects, 65 (8.9%) had EE. The EE patients had higher body mass index, metabolic syndrome prevalence, triglyceride levels, and blood pressure (P < 0.05). The mean VFA/SFA ratio was higher in the EE group than in the non-EE group (1.30 vs. 0.92, P < 0.001). The predominance of EE in the group with higher VFA/SFA ratio was higher than in the group with lower VFA/SFA ratio (P < 0.001). A VFA/SFA ratio ≥1.165 had good accuracy to predict EE (area under the receiver-operating characteristic curve, 0.643). The VFA/SFA ratio and visceral fat volume were positively correlated with the severity of EE (P = 0.002), and a VFA/SFA ratio ≥1.165 was strongly correlated with the severity of EE (P < 0.001).ConclusionThe high VFA/SFA ratio can be a useful clinical predictor of EE.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

AIMTo elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice.METHODSThe study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed.RESULTSThe FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients’ GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers (RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers (total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01).CONCLUSIONApproximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

PTH-190 Optimisation of the peptest diagnostic test for detection of gord using pepsin as a marker: an ideal primary care tool: Abstract PTH-190 Table 1

Introduction The diagnostic test Peptest™ detects pepsin, which is exclusively produced by the stomach, in expectorated saliva and is a quick and easy unique marker of the reflux of gastric contents responsible for gastro-oesophageal reflux disease (GORD).1 A study into the ability of Peptest to detect patients with GORD was performed. The optimal sampling strategy to give the highest diagnostic yield was investigated. Method Patients attending routine endoscopy clinic at Rotherham General Hospital with symptoms of GORD with erosive oesophagitis (EO) or if the score of the GERDQ2was ≥8. The patients provided 1–10 saliva samples with randomised strategies thats were blindly analysed for the presence of pepsin using Peptest™ and concnof pepsin determined (≥16ng/ml). Results 59 GORD subjects (30M:27F; mean age 57; 83% on PPI) provided 283 expectorated saliva samples of which 149 samples (53%) were Peptest positive representing 47 GORD subjects with at least 1 Peptest positive sample (80%) [significantly greater than a control group138%, p Pepsin concnranged from 0–500 ng/ml with median 30 ng/ml (IQR 0–164) and mean 94 ng/ml (SD 133) [significantly greater than a control group1p There were 22 patients with EO, 35 patients with non-erosive reflux disease (NERD) and 2 patients with Barrett’s Oesophagus (BO) with at least 1 sample pepsin positive: 68% for EO (mean 68 ng/ml), 86% for NERD (mean 105 ng/ml) and 100% (mean 152 ng/ml) for BO. Peptest results based on timing of the sample is given in Table 1. Conclusion Optimal sampling time for diagnosis of GORD by Peptest is 60 min after a meal or within 15 min of a symptomatic episode. The ease of the test allows for saliva samples to be taken before commencing treatment, but even amongst pre-treated EO patients (where gastroscopy is often negative) Peptest can still recognise the underlying reflux. Peptest, therefore, has the potential to be used as the first line investigation in patients suspected of reflux. Those without ‘alarm’ symptoms and who test ‘positive’ could therefore be managed in general practice. Referral for gastroscopy or for other invasive investigations can be reserved for those for whom there is separate need (e.g. to check BO, if reflux symptoms are refractory, or for opportunistic cancer screening). Disclosure of interest V. Strugala Employee of: RD Biomed Ltd, P. Dettmar Shareholder of: RD Biomed Ltd, Conflict with: RD Biomed Ltd, K. Bardhan: None Declared. Study was part funded by Technology Strategy Board References Hayat JO, et al. Gut 2015;64:373–380 Jones R, et al. APT 2009;30(10):1030–1038

Correlation Between Gastroesophageal Reflux Disease Questionnaire and Erosive Esophagitis in School-aged Children Receiving Endoscopy

The gastroesophageal reflux disease (GERD) questionnaire (GerdQ) is a validated questionnaire that was developed recently to help identify GERD patients. The sensitivity and specificity of GerdQ for the diagnosis of GERD in adult patients were 65% and 71%, respectively. Because the application of GerdQ in pediatric population is largely unknown, the aim of this study is to establish the endoscopic correlation between Chinese GerdQ and grades of erosive esophagitis (EE) in Taiwanese children. Seventy-four children (aged 9-18 years) were evaluated by our version of the Chinese GerdQ prior to receiving esophagogastroduodenoscopy for warning upper gastrointestinal symptoms. Grades of EE were assessed blindly, according to the Los Angeles classification. The sensitivity and specificity of GerdQ for detecting endoscopic EE were analyzed. In 74 patients, the male to female ratio was 1:1.1 and the mean age was 14.2 ± 2.3 years (age range: 9.2-17.9 years). Thirty-nine percent of the enrolled patients had EE. The sensitivity and specificity of GerdQ (with a cutoff score of ≥7) to identify EE patients were 65.5% and 80%, respectively. The odds ratio of GerdQ for a cutoff score of 7 to identify EE was 7.6 (95% confidence interval = 2.6-21.9, p < 0.001). For the identification of EE in children, the Chinese GerdQ had similar sensitivity and specificity to that used for adults. This questionnaire may be applied as a noninvasive screening tool.

Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non‐erosive reflux disease patients

Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure.

Distinguishing the impact of dexlansoprazole on heartburn vs. regurgitation in patients with gastro‐oesophageal reflux disease

Gastro-oesophageal reflux disease (GERD) is characterised by symptomatic heartburn and regurgitation. Treatment with proton pump inhibitors (PPI) effectively decreases heartburn symptoms, but their effects on symptomatic regurgitation are less clear. To determine the impact of PPI therapy on heartburn and regurgitation severity in patients with either non-erosive GERD (NERD) or erosive oesophagitis (EE). Endoscopically-confirmed NERD patients received dexlansoprazole 30 or 60 mg or placebo in a randomised, blinded, 4-week study. Endoscopically-confirmed EE patients received dexlansoprazole 60 mg or lansoprazole 30 mg in two 8-week, randomised, blinded healing studies. The Patient Assessment of Upper Gastrointestinal Symptom Severity questionnaire, which includes a heartburn/regurgitation subscale, was administered to assess symptom severity at baseline, and at weeks 2 and 4 of the NERD study and at weeks 4 and 8 during the EE trials. We defined separate subscales for heartburn and regurgitation for this post-hoc analysis. Among patients with both symptoms at baseline, improvements in individual heartburn and regurgitation subscales along with the original combined heartburn/regurgitation subscale were determined. In the NERD and EE studies, 661 and 1909 patients, respectively, had both heartburn and regurgitation at baseline. NERD patients receiving dexlansoprazole 30 and 60 mg experienced significantly greater improvements in symptom severity for both heartburn and regurgitation compared with placebo. EE patients receiving dexlansoprazole 60 mg had significantly greater improvements in heartburn/regurgitation and heartburn-only subscales at week 4 compared with those receiving lansoprazole. Dexlansoprazole appears to be effective in improving both heartburn and regurgitation, and this improvement is maintained for the duration of treatment.

Obesity Does Not Affect Treatment Outcomes With Proton Pump Inhibitors

Obesity is associated with increased risk of gastroesophageal reflux disease (GERD). To evaluate the effect of obesity on symptom resolution in patients with nonerosive reflux disease (NERD) and healing rates in patients with erosive esophagitis (EE). Two post hoc analyses were performed. Analyses included pooled data from randomized, double-blind, multicenter studies of proton pump inhibitors (PPIs) in GERD patients. Analysis 1 included 704 patients with NERD receiving esomeprazole 20 mg, esomeprazole 40 mg, or placebo. Analysis 2 included 11,027 patients with EE receiving esomeprazole 40 mg, omeprazole 20 mg, or lansoprazole 30 mg. For NERD patients, no significant association between baseline heartburn severity and body mass index (BMI) was observed. In EE patients, overweight (BMI 25 to <35 kg/m) and obese (BMI ≥35 kg/m) patients had significantly higher rates of Los Angeles (LA) grade C or D EE than patients with BMI <25 kg/m (P<0.0001). Percentages of PPI-treated patients who achieved heartburn resolution or EE healing within a given LA grade were similar across BMI categories. Heartburn resolution was significantly associated with treatment (esomeprazole vs. placebo), increasing age, and for men versus women (all P≤0.0284). EE healing was significantly associated with PPI treatment (esomeprazole and lansoprazole vs. omeprazole), increasing age, race, presence of a hiatal hernia, and lower LA grade at baseline (all P≤0.0183). In patients with GERD, high BMI was associated with more severe EE at baseline. However, during PPI treatment, BMI is not a significant independent predictor of heartburn resolution or EE healing.

The effects of increasing body mass index on heartburn severity, frequency and response to treatment with dexlansoprazole or lansoprazole

BackgroundHigher body mass index (BMI) is a recognised risk factor for gastro-oesophageal reflux disease (GERD). Data regarding the impact of BMI on proton pump inhibitor (PPI) therapy are conflicting.AimTo assess the impact of BMI on baseline heartburn symptom severity and frequency and response to PPI therapy in patients with non-erosive GERD (NERD) or erosive oesophagitis (EO).MethodsIn post hoc analyses of phase 3 trial data, 621 NERD and 2692 EO patients were stratified by BMI (<25, 25 to <30 and ≥30 kg/m2). NERD patients received either dexlansoprazole MR 30 mg or placebo daily for 4 weeks. EO patients received either dexlansoprazole MR 60 mg or lansoprazole 30 mg for 8 weeks. Symptom frequency and severity were assessed at baseline and subsequently by daily diary.ResultsIn both the NERD and EO cohorts, baseline heartburn severity increased with increasing BMI. The impact of PPI therapy on the reduction in heartburn symptom frequency and severity in both NERD and EO patients was similar across BMI categories. EO healing rates in patients treated with dexlansoprazole but not lansoprazole were higher in obese patients compared with those with a BMI <30 kg/m2. Differences between the PPIs were small.ConclusionsThe PPIs evaluated in this study reduced the frequency and severity of 24-h heartburn regardless of baseline BMI. In addition, because patients with higher BMI have more severe symptoms at baseline, they may experience greater therapeutic gain with dexlansoprazole (NERD and erosive oesophagitis) and possibly lansoprazole (erosive oesophagitis) treatment.

Esophageal Dysmotility Increases with the Severity of Gastroesophageal Reflux Disease: A Study Using High Resolution Manometry and the Revised Chicago Classification Criteria

Purpose: Past studies utilizing the conventional manometric definition of Ineffective Esophageal Motility have yielded conflicting results regarding the prevalence of dysmotility among GERD subgroups. Recently, the International High Resolution Manometry (HRM) Working Group issued new definitions for peristaltic function using the Chicago Classification (CC). The purpose of this study was to apply the new CC criteria to determine the prevalence of dysmotility among patients with Erosive Esophagitis (EE), Non-Erosive Reflux Disease (NERD) and Functional Heartburn (FH). Methods: A retrospective review of 150 patients who underwent HRM for GERD symptoms was performed. Patients were divided into 3 groups based upon endoscopic and esophageal pH or impedance testing: 1) EE (Esophagitis on EGD) (n=50), 2) NERD (normal EGD and pathological acid exposure on pH Testing or > 48 reflux events on impedance) (n=63), 3) FH (normal EGD, normal pH or impedance) (n=37). HRM studies were then characterized using the CC for peristaltic abnormalities and Esophagogastric Junction (EGJ) types. Results: The most common pattern among FH patients was normal motility (68%) which was higher than in the EE (12%, p<0.0001) and NERD (37%, p=0.004) groups. The FH group could be distinguished from NERD patients with lower rates of Weak Peristalsis with Large Peristaltic Defects (Figure 1). Comparisons between FH and EE yielded lower rates for Absent Peristalsis (0% vs 14%, p=0.018), Frequent Failed Peristalsis (0% vs 14%, p=0.018) and Weak Peristalsis with Large Peristaltic Defects (14% vs 42%, p=0.005). EE patients could be distinguished from the NERD group based upon higher rates of Absent Peristalsis (Figure 1). EGJ type 2 (1-2 cm separation between the crural diaphragm and lower esophageal sphincter) was more common in EE (30%) and NERD (29%) than in FH (11%) (p=0.038, p=0.047). EGJ type 3 (> 2 cm separation) also differentiated EE (20%) patients from FH (3%) (p=0.021).Figure: Prevalence of motility patterns among gerd subtypes using the revised chicago classification for high resolution esophageal manometry.Conclusion: HRM patterns for peristaltic dysfunction and the EGJ are different among GERD subgroups. Esophageal dysmotility characterized by the new Chicago Classification guidelines increases with the severity of esophageal acid exposure.

Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn

Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH). Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n=5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35. The prevalence of ME was higher (p<0.0001) in EE (95%), pH-POS (77%), and HE (65%) NERD patients than in FH patients (13%) and HVs (15%). Also, basal cell hyperplasia (p<0.0023), DIS (p<0.0001), and papillae elongation (p<0.0002) showed similar rates of prevalence in the above populations (p<0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p=0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p<0.0001 and p<0.0001, respectively). The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.

Comparison of Distribution of Intraesophageal pH During Nighttime Recumbency Among Patients With Gastroesophageal Reflux Disease

Nighttime reflux has been demonstrated to be associated with a more aggressive presentation of gastroesophageal reflux disease (GERD). However, it has remained unknown until now if the difference in nighttime reflux between the different GERD groups is related to the distribution of intraesophageal pH level or duration of acid exposure. To compare distribution of intraesophageal pH during nighttime between patients with erosive esophagitis (EE) versus those with nonerosive reflux disease (NERD). Patients with heartburn symptoms at least 3 times per week were included in this study. Patients were not receiving any antireflux treatment. All patients underwent an upper endoscopy to determine if esophageal inflammation was present or absent. Subsequently, patients underwent ambulatory 24-hour esophageal pH monitoring. Only those with NERD and EE were included in this study. Nighttime period was defined as the time from the moment patients entered the bed to fall asleep and until they woke up the next morning. Distribution of intraesophageal pH during nighttime was generated using a special computer program that analyzed all registered pH measurements. Nineteen patients were found to have NERD and 31 EE. Time in bed was not different between the 2 groups. The mean number of acid reflux events, mean reflux time pH<4, and mean % total time pH<4 during nighttime were significantly lower in the NERD group as compared with the EE group (13.05±4.6, 19.7±7.09, 3.6±1.2% vs. 25.44±4.4, 29.3±7.97, 5.3±1.5%, respectively, all P<0.05). Symptom index for EE was 43.8% versus 21% for NERD, P<0.05. Overall, the distribution of intraesophageal pH during nighttime was similar between NERD and EE patients for all pH ranges. Patients with EE demonstrated a significantly higher nighttime esophageal acid exposure as compared with NERD, but the overall distribution of the acid exposure was similar between the 2 groups. This suggests that duration rather than intensity of nighttime intraesophageal acid exposure accounts for the difference between EE and NERD.