DEMOGRAPHIC AND CLINICAL FEATURES HELP TO IDENTIFY NON EROSIVE REFLUX DISEASE (NERD) PATIENTS WITH ABNORMAL pH-IMPEDANCE TESTING
Edoardo SavarinoPatrizia ZentilinPietro DulbeccoGiorgio SammitoElisa MarabottoLuca Maria SconfienzaMassimo CorboS. VigneriC. MansiAurora ParodiVincenzo Savarino
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Gastroesophageal reflux disease (GERD) is one of the most common gastroenterological diseases. For a long time, GERD was considered as a continuum of various pathological conditions based on the degree of dysfunction of the lower esophageal sphincter, from non‑erosive GERD (NERD) and reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma. Currently, the views on the GERD pathophysiology have significantly changed. To date, it is believed that various presentations of GERD represent its individual phenotypes with unique predisposing cofactors and pathophysiology outside this paradigm. Different GERD phenotypes include NERD, reflux esophageal hypersensitivity, functional heartburn, low and high degree reflux esophagitis, Barrett’s esophagus, regurgitation‑dominant GERD, extra‑esophageal GERD, and reflux chest pain syndrome. Due to the fact that not all GERD phenotypes are the same, clinical management of GERD patients should be carried out differentially, depending on the unique pathophysiological features of each phenotype. The time has come to apply a personalized approach to the management of patients with various GERD phenotypes, which will undoubtedly improve the results of treatment of this heterogeneous and extremely widespread pathology in the future.
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Heartburn
Esophagitis
Reflux esophagitis
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Non-erosive reflux disease (NERD) is the most common presentation of gastroesophageal reflux disease. Although acid reflux is the most important cause of symptom generation in NERD patients, non-acid reflux is also associated with reflux symptoms. The temporal relation between symptoms and reflux episodes is of importance in evaluating the results of combined pH-impedance monitoring in NERD patients. Mucosal hypersensitivity and mechanical stimulation due to great volume of non-acid reflux are among the putative mechanisms of symptom generation.
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The evaluation of the success of therapy for gastroesophageal reflux disease (GERD) has thus far been primarily on the basis of the endoscopic evaluation of the ability of drugs to heal esophageal mucosal breaks and to a lesser extent on their ability to decrease the diverse symptoms of acid reflux. However, because most patients with GERD have no visible esophageal lesions using conventional endoscopic methods, this paradigm requires serious reconsideration. As patients with nonerosive reflux disease (NERD) are just as symptomatic as patients with erosions and are no easier to treat the use of endoscopic end points alone, as criteria for determining healing and efficacy of therapy requires reassessment. In addition, the symptoms of GERD are now appreciated to be broad-based, including many extraesophageal symptoms that contribute to the marked reduction in quality of life for GERD patients. For this reason, and because endoscopic criteria cannot be applied to evaluating therapy in NERD, the success of GERD therapy should be judged primarily in terms of diminishment of GERD-related symptoms--a return to the traditional way that patients judge therapeutic success. To objectively determine the success of therapy in GERD, multisymptom GERD questionnaires have been developed. The most promising are those that reflect the numerous types of GERD symptoms, are patient-administered, quantitative, responsive, and have been validated in both NERD and erosive GERD patients. The ReQuest instrument is especially attractive as it records the entire range of GERD symptoms on a daily basis (including also their frequency and intensity) and is responsive to changes with time and with therapy. Symptom-based evaluative tools should greatly aid the objective evaluation of GERD symptoms, monitor precisely how patients respond to therapy and thereby lead to improvements in GERD management.
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In Japan prevalence of GERD is still low as compared to Western countries. Although it is almost certain that the number of GERD patients will not increase by increasing patients who will receive eradication in Western countries, it may be the case in Japan, because most of the H. pylori-infected subjects in Japan have a considerable level of mucosal atrophy, that can be improved after eradication of H. pylori. Indeed, prevalence of H. pylori in Japanese patients with GERD is reported to be approximately 30-40%, suggesting protective role of H. pylori infection in the development of GERD. The disease entity of Non-erosive GERD (NERD) is receiving great attention recently, but effective rate of PPI for NERD is reported to be 60%, suggesting that a considerable number of non-GERD patients are included in patients diagnosed as having NERD. Thus, an effort for improving both sensitivity and specificity of the diagnosing method for NERD is required. In any event, it should be kept in mind that pathophysiology of GERD is quite different between Western and Japanese patients.
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Cisapride
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Esophagitis
Lansoprazole
Heartburn
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To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings.Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups.Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group (P < 0.05).The patients in NERD group showed significantly increased total reflux episode, mixed reflux episode, proximal acid reflux episode, proximal weak acid reflux episode, total proximal reflux episode, percentage of proximal acid reflux, percentage of proximal weak acid reflux, and percentage of total proximal reflux as compared with the other two groups (all P < 0.05).Bolus clear time was significantly prolonged in NERD group compared with that in the other two groups (P < 0.05).Analysis of the reflux acidity showed that the percentages of different reflux episodes differed significantly among the 3 groups (P < 0.05);acid reflux was the main reflux in NERD, while weak acid reflux was the main reflux in RH and FH groups, which had also significantly increased weakly alkaline reflux episodes compared with NERD group.Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.
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Heartburn
Esophageal pH monitoring
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Abstract In patients with proton pump inhibitor-resistant non erosive reflux disease (NERD) having symptoms associated with liquid reflux, there are reports that reflux symptoms are more likely to be caused by the proximal extent of the reflux and reflux where pH <5. The objective of this study was to investigate the relationships between symptoms, reflux pH values, and the extent of reflux in patients with potassium-competitive acid blocker (P-CAB)-resistant NERD. Methods The subjects were 20 patients with P-CAB-resistant NERD whose symptoms did not improve even after administration of P-CAB (vonoprazan 20 mg/day) for 2–4 weeks. Their symptom index was positive for liquid reflux in impedance–pH monitoring. We investigated reflux pH values in symptomatic and asymptomatic reflux events, proportion of symptomatic reflux events according to the reflux pH value (pH <5 or ≥ 5), proportion of symptomatic reflux events at each impedance site, and proportion of symptomatic reflux events at each impedance site according to the reflux pH value (pH <5 or ≥ 5). Results About 60% of the symptomatic reflux events were caused by reflux with pH ≥5 in patients with P-CAB-resistant NERD. The median reflux pH value for total reflux events was 5.3 and that for symptomatic reflux events was 5.2. The proportion of symptomatic reflux events caused by reflux with pH <5 was significantly higher than that caused by reflux with pH ≥5. Symptomatic reflux events for reflux with pH <5 are more likely to be caused by proximal extent. There was no difference in the proportion of symptomatic reflux events for reflux with pH ≥5 at each reflux extent site. Conclusion In patients with P-CAB-resistant NERD, their symptoms were often caused by reflux with pH ≥5. A difference in the relationship between the reflux extent site and appearance of symptoms was observed according to the reflux pH value.
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Esophageal pH monitoring
Reflux esophagitis
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