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Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy.

ABSTRACT: About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.

SUBMITTER: Ang D

PROVIDER: S-EPMC5075954 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy.

Ang Daphne D How Choon How CH Ang Tiing Leong TL

Singapore medical journal 20161001 10

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac a ...[more]

PMID: 27779277

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Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.

Project description:BackgroundA substantial proportion of patients with gastro-oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying.AimTo evaluate the effect of revexepride, a novel prokinetic 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs.MethodsA phase 2b, double-blind, parallel-group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e-diary data captured patients' symptoms over an 8-week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation-free days in the second half of the study (weeks 5-8).ResultsIn total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation-free days increased from baseline (range, 15.0-18.8%) to week 8 (62.3-70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose-dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment-emergent adverse events (TEAEs) was revexepride dose-dependent. Only one serious TEAE occurred and none resulted in death.ConclusionsRevexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.

| S-EPMC5024018 | biostudies-literature

Gastro-oesophageal reflux disease.

Project description: Not available

| S-EPMC1326932 | biostudies-literature

Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms.

Project description:Background & aimsThere are few data on the prevalence of gastroesophageal reflux disease (GERD) in the United States. We performed a population-based study to determine the prevalence of GERD symptoms and persistent GERD symptoms despite use of proton pump inhibitors (PPIs).MethodsWe conducted the National Gastrointestinal Survey in 2015 using MyGiHealth, an app that guides participants through National Institutes of Health gastrointestinal Patient-Reported Outcomes Measurement Information System surveys. Primary outcomes were prevalence of GERD symptoms in the past and persistence of GERD symptoms (heartburn or regurgitation 2 or more days in past week) among participants taking PPIs. Population weights were applied to the data and multivariable regression was used to adjust for confounding.ResultsAmong 71,812 participants, 32,878 (44.1%) reported having had GERD symptoms in the past and 23,039 (30.9%) reported having GERD symptoms in the past week. We also found that 35.1% of those who had experienced GERD symptoms were currently on therapy (55.2% on PPIs, 24.3% on histamine-2 receptor blockers, and 24.4% on antacids). Among 3229 participants taking daily PPIs, 54.1% had persistent GERD symptoms. Younger individuals, women, Latino individuals, and participants with irritable bowel syndrome or Crohn's disease were more likely to have continued symptoms, even when taking PPIs.ConclusionsUsing a population-based survey, we found GERD symptoms to be common: 2 of 5 participants have had GERD symptoms in the past and 1 of 3 had symptoms in the past week. We also found that half of PPI users have persistent symptoms. Given the significant effect of GERD on quality of life, further research and development of new therapies are needed for patients with PPI-refractory GERD symptoms.

| S-EPMC7103516 | biostudies-literature

Prevalence of gastro-oesophageal reflux disease symptoms and reflux-associated respiratory symptoms in asthma.

Project description:BACKGROUND: Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use. METHODS: A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms. RESULTS: The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); P < 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (P < 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms. CONCLUSIONS: GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms.

| S-EPMC2954896 | biostudies-other

Respiratory and laryngeal symptoms secondary to gastro-oesophageal reflux.

Project description:Gastro-oesophageal reflux may cause a range of laryngeal and respiratory symptoms. Mechanisms responsible include the proximal migration of gastric refluxate beyond the upper oesophageal sphincter causing direct irritation of the larynx and lower airway. Alternatively, refluxate entering the distal oesophagus alone may stimulate oesophageal sensory nerves and indirectly activate airway reflexes such as cough and bronchospasm. Recognising reflux as a cause for these extraoesophageal symptoms can be difficult as many patients do not have typical oesophageal symptoms (eg, heartburn) and clinical findings on laryngoscopy are not very specific. Acid suppression remains an effective treatment in the majority of patients but there is growing appreciation of the need to consider and treat non-acid and volume reflux. New opinions about the role of existing medical and surgical (laparoscopic techniques) treatment are emerging and a number of novel anti-reflux treatments are under development.

| S-EPMC5517228 | biostudies-other

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial.

Project description:Background and aimsProton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs.MethodsThis double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD).ResultsOf 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P = .04).ConclusionsAmong patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

| S-EPMC7755671 | biostudies-literature

Randomised trials of proton pump inhibitors for gastro-oesophageal reflux disease in patients with asthma: an updated systematic review and meta-analysis.

Project description:ObjectiveAsthma often coexists with gastro-oesophageal reflux disease (GERD). The effect of proton pump inhibitors (PPIs) treatment on asthma concomitant with GERD was inconsistent. This study aimed to assess whether PPIs treatment improved morning peak expiratory flow (mPEF) in asthma patients with GERD.Data sourcesPubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov; hand searching for reference lists; contacted with authors if necessary.Study selectionAll eligible trials were randomised clinical trials comparing PPIs with placebo in asthma patients accompanying with GERD.ResultsFourteen randomised clinical trials (2182 participants) were included. Overall, PPIs versus placebo did not affect mPEF in patients with asthma having GERD (weighted mean difference 8.68 L/min, 95% CI -2.02 to 19.37, p=0.11). Trial sequential analysis (TSA) further confirmed this finding (TSA adjusted 95% CI -1.03 to 22.25). Subgroups analyses based on the percentage of patients with symptomatic GERD≥95%, treatment duration >12 weeks also found no statistically significant benefit on mPEF. Similarly, analyses of secondary outcomes (evening PEF, forced expiratory volume in 1 s, asthma symptoms score, asthma quality of life score and episodes of asthma exacerbation) did not show significant difference between PPIs and placebo.ConclusionIn this meta-analysis, PPIs therapy did not show a statistically significant improvement on mPEF in asthma patients having GERD, neither in subgroup with symptomatic GERD nor in subgroup with treatment duration >12 weeks. This analysis does not support a recommendation for PPIs therapy as empirical treatment in asthma patients with GERD.Prospero registration numberCRD42020177330.

| S-EPMC8356177 | biostudies-literature

Comparison of gastroesophageal reflux disease symptoms and proton pump inhibitor response using gastroesophageal reflux disease impact scale questionnaire.

Project description:BACKGROUND/AIMS:To compare gastroesophageal reflux disease (GERD) symptoms and response to proton pump inhibitor (PPI) in patients with erosive esophagitis (EE), non-erosive reflux disease (NERD) or functional heartburn (FH) using GERD impact scale (GIS) questionnaire. METHODS:Total 126 patients with GERD symptoms were diagnosed as EE (n = 62), NERD (n = 34) and FH (n = 30) by endoscopy, 24-hour esophageal pH testing and Bernstein test, prospectively. Analysis of risk factors and GIS questionnaire for GERD symptoms and quality of life were performed before and 8 weeks after PPI treatment. RESULTS:EE group had a higher proportion of men, frequent alcohol consumption, smoking, hiatal hernia, body mass index ? 25 kg/m(2) and triglyceride levels (? 150 mg/dL) than the other groups (all P < 0.05). On the other hand, both psychiatric treatment and psychopharmacotherapy were more frequent in patients with FH than in those with EE and NERD (both P < 0.05). Among GERD symptoms, chest pain was more frequent in FH group than in EE and NERD groups (P < 0.05). Eating problems and limitation of productive daily activities occurred frequently in FH group and NERD group, respectively. GIS after 8 week PPI treatment showed improvement in all of the GERD symptoms in EE (all P < 0.05) and in acid regurgitation, epigastric pain and hoarseness in NERD group (all P < 0.05). In terms of quality of life, PPI treatment improved sleep disturbance in EE (P = 0.031) and limitation of productive activity in the NERD group (P = 0.001). CONCLUSIONS:GIS questionnaire showed that different characteristics and symptoms improved after PPI therapy among patients with EE, NERD and FH, demonstrating the usefulness of the GIS questionnaire.

| S-EPMC3548129 | biostudies-literature

Efficacy of Vonoprazan for Gastroesophageal Reflux Symptoms in Patients with Proton Pump Inhibitor-resistant Non-erosive Reflux Disease.

Project description:Objective Clinically, patients with proton pomp inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD) are very challenging to treat. The aim of this study was to determine the rates of symptom relief and adverse events among PPI-resistant GERD patients that changed their therapy from a PPI to vonoprazan. Methods Patients with severe gastroesophageal reflux symptoms (total GERD-Q score ?8) without endoscopic findings of mucosal breaks who changed their medication from a PPI to vonoprazan during a 12-week period from 2015 to 2016 at 2 hospitals were selected. The primary outcome was the self-reported relief of gastroesophageal reflux symptoms. The odds ratio (OR) for the improvement of symptoms was calculated based on an exact binomial distribution using a matched-pair analysis. The secondary outcome was the GERD-Q score and adverse events. Results Twenty-six patients (6 men) with a mean age of 67.5 years were analyzed. After the therapy was changed from a PPI to vonoprazan, 18 patients (69.2%) reported an improvement, 6 (23.1%) reported no change, and 2 (7.7%) reported an exacerbation of symptoms. A change in therapy was significantly associated with improved self-reported symptoms (OR 9.0, p<0.001). The mean total GERD-Q score during vonoprazan treatment was significantly lower than that during PPI therapy (11.96 vs. 8.92). There were no significant differences in the incidence of adverse events between the therapies. Conclusion Changing the medication from a PPI to vonoprazan was significantly associated with an improvement in gastroesophageal reflux symptoms. Vonoprazan is one of the most promising treatment options for patients with PPI-resistant GERD.

| S-EPMC6172555 | biostudies-literature

The management of gastro-oesophageal reflux disease.

Project description:If there are no features of serious disease, suspected gastro-oesophageal reflux disease can be initially managed with a trial of a proton pump inhibitor for 4-8 weeks. This should be taken 30-60 minutes before food for optimal effect. Once symptoms are controlled, attempt to withdraw acid suppression therapy. If symptoms recur, use the minimum dose that controls symptoms. Patients who have severe erosive oesophagitis, scleroderma oesophagus or Barrett's oesophagus require long-term treatment with a proton pump inhibitor. Lifestyle modification strategies can help gastro-oesophageal reflux disease. Weight loss has the strongest evidence for efficacy. Further investigation and a specialist referral are required if there is no response to proton pump inhibitor therapy. Atypical symptoms or signs of serious disease also need investigation.

| S-EPMC4816873 | biostudies-literature

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