Drugs, bugs, and esophageal pH profiles

Until relatively recently, gastroesophageal reflux disease (GERD) was thought to be a relatively trivial problem, and pharmaceutical companies initially had remarkably little interest in clinical trials for GERD. Over the last ten years, GERD therapy has become the subject of intense interest, since reflux disease is now recognized as a major market for antisecretory and prokinetic drugs. Even low-technology antacids are now known to effectively neutralize esophageal acid prevent acid reflux for up to 90 minutes. Esophageal pH profiling is known to be an excellent surrogate for clinical efficacy of GERD drugs, particularly in erosive esophagitis. Years ago, famotidine normalized esophageal mucosal exposure to pH < 4.0 only when administered in doses of 40 mg twice a day. Subsequent studies confirmed that multiple daily dosing of histamine-2 receptor antagonists (H2RAs) was mandatory for GERD treatment, with clear dose-response relationships for each agent. Proton pump inhibitors (PPIs) have each been carefully assessed in terms esophageal and gastric pH profiles. Omeprazole has a particularly flat dose response curve, making it difficult to differentiate pH or clinical effects of 20 vs. 40 mg doses. Improved rapidity of onset and/or enhanced potency is demonstrable in pH data obtained with lansoprazole, rabeprazole and pantoprazole. Such differences will translate to improved clinical efficacy, based on the meta-analyses of Richard Hunt and his group in Canada that correlate pH effects and symptom relief/healing. PPI's have dependably surpassed H2RAs and prokinetic drugs in management of the more severe grades of esophagitis. Helicobacter pylori has a peculiar relationship to GERD. There has been some concern that PPIs given to patients with H. pylori might accelerate development of severe atrophic gastritis. It is also now known that eradication of H. pylori may increase symptomatic GERD (possibly as a result of increased gastric acid secretion once the bacteria have been eliminated). New data confirm nocturnal breakthrough of acid secretion and esophageal acid exposure in three-fourths of patients on omeprazole 20 mg twice daily. This nocturnal acidity can be controlled more effectively with a nighttime dose of an H2RA than with a third dose of omeprazole. Control of acid secretion and improved gastric and esophageal pH profiles are goals of modern GERD therapy, and the product that most cost effectively normalizes esophageal acid exposure will have a substantial advantage in the ever-growing GERD marketplace.     

Helicobacter pylori, proton pump inhibitors and gastroesophageal reflux disease

Proton pump inhibitors have become of pivotal importance for the treatment of GERD. The purpose of this paper is to review the interaction between Helicobacter pylori and PPIs in the treatment of GERD. H. pylori exaggerates the acid suppressive effects of PPIs. During treatment with these drugs, H. pylori-positive subjects thus have a higher intragastric pH than H. pylori-negative subjects. The mechanism for this phenomenon remains to be elucidated. We hypothesize that it is related to H. pylori-induced corpus gastritis, which impairs parietal cell function. The available evidence suggests that this phenomenon has no clinical relevance for the treatment of GERD. The 24-hr esophageal pH during PPI treatment does not depend on the H. pylori status, nor does the medication dose needed for maintenance therapy or the number of clinical relapses during such therapy depend on the H. pylori status. PPIs, on the other hand, also affect H. pylori. During treatment with these drugs, the pattern of bacterial colonization and associated gastritis shifts proximally. The increased gastritis of the body mucosa is associated with a more rapid development of atrophic gastritis, a condition characterized by a loss of gastric glands and associated with an increased cancer risk. For these reasons, one has to consider H. pylori eradication in infected GERD patients in need of PPI maintenance therapy.     

Nocturnal acid breakthrough - approach to management

Nocturnal acid breakthrough is defined as the presence of intragastric pH < 4 during the overnight period for at least 60 continuous minutes in patients taking a proton-pump inhibitor (PPI). Nocturnal acid breakthrough occurs in more than 70% of Helicobacter pylori-negative patients on PPI therapy and has clinical consequences in particular in patients with complicated gastroesophageal reflux disease (GERD), Barrett's esophagus, and esophageal motility abnormalities. The clinical importance of nocturnal acid breakthrough and the benefit of adding histamine-2 receptor antagonists (H2RAs) to PPI therapy have been debated ever since these concepts were introduced. In our experience, the addition of bedtime H2RAs is clinically effective in controlling nocturnal acid breakthrough and GERD symptoms.     

Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Background

Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.

Materials and Methods

This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.

Results

Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.

Conclusion

Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.     

Active and inactive gastroesophageal reflux diseases related to Helicobacter pylori therapy

We systematically reviewed the literature on gastroesophageal reflux disease (GERD) related to Helicobacter pylori therapy, and classified the GERD according to various aspects. Preexisting GERD is active GERD before H. pylori therapy, and a substantial proportion of the GERD patients improve after successful H. pylori therapy. If the GERD does not persist or recur after cessation of acid-suppressive therapy combined with H. pylori therapy, it may have been cured (cured GERD). If it recurs, it may have been masked by acid-suppressive therapy and unmasked with cessation of the therapy (pharmacologically masked and unmasked GERD). Newly developed GERD after successful H. pylori therapy is a kind of unmasked GERD arising after cure of infection (de novo unmasked GERD). The possible mechanism of the improvement of cured GERD is normalized hyperacidity associated with an improved cytokine-somatostatin-gastrin system followed by normalized G-cell activity and parietal cell mass. Preexisting GERD is not a reason to avoid eradication therapy. De novo unmasked GERD develops in a substantial proportion of patients with cured infection. The possible mechanism is increased acid exposure in the esophagus due to gastric acid increase, which is caused by a loss of neutralizing effect by ammonia, normalized cytokine-acid suppression and improvement of corpus atrophy. De novo unmasked GERD is important because GERD is recurrent and may induce adenocarcinoma of the esophagus. However, it is expected that cure of infection lowers gastric cancer incidence. Eradication therapy is recommended irrespective of the possibility that de novo unmasked GERD may have a slight increase of the risk of esophageal adenocarcinoma.     

Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

Proton pump inhibitors(PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease(GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls(HCs) using 16 S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPIuser and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae,Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on shortterm PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.     

Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19

The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.     

The Association between Histamine 2 Receptor Antagonist Use and Clostridium difficile Infection: A Systematic Review and Meta-analysis

Background

Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI.

Purpose

We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H₂RAs) and CDI.

Data source

We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H₂RAs and CDI.

Study selection

Two authors independently reviewed the studies for eligibility.

Data extraction

Data about studies characteristics, adjusted effect estimates and quality were extracted.

Data synthesis

Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H₂RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I² = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H₂RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097).

Conclusion

In this rigorous systematic review and meta-analysis, we observed an association between H₂RAs and CDI. The absolute risk of CDI associated with H₂RAs is highest in hospitalized patients receiving antibiotics.     

Changing patterns of Helicobacter pylori gastritis in long-standing acid suppression

Background. Helicobacter pylori colonization and associated inflammation are influenced by local acid output. Infected subjects with acid‐related diseases, such as gastroesophageal reflux disease (GERD) are likely to have an antral‐predominant gastritis. We hypothesized that long‐term acid suppression would result in relatively greater bacterial colonization in the corpus leading to diffuse or corpus‐predominant gastritis and that this would be prevented by prior H. pylori eradication. Materials and Methods. To investigate this, we conducted a prospective, double‐blind trial of the effect on gastric histology of 12‐month maintenance treatment with omeprazole in H. pylori–positive GERD patients randomly assigned to either an eradication or omeprazole‐alone regime. A control group of 20 H. pylori–negative GERD patients also received omeprazole throughout the study period. Biopsies taken at baseline and at 12 months were graded “blind” by a single observer according to the updated Sydney System. The 41 H. pylori‐positive subjects with grade B or C esophagitis were randomly assigned (20 to omeprazole alone, 21 to eradication) and 33 subjects completed the 12‐month study. Results. There was a significant decline in antral chronic inflammation in initially positive patients between baseline and end in both the eradication group (p = .035) and the omeprazole‐alone group (p = .008). However, corpus chronic inflammation increased in the omeprazole‐alone group (p = .0156) but decreased in the eradication group. The change toward corpus predominance between baseline and end for the omeprazole‐alone group is highly significant (p = .0078). Furthermore, 5 of 11 in the omeprazole‐alone group developed mild corpus atrophy, compared to 0 of 8 who had undergone H. pylori eradication. The change in frequency of corpus atrophy between the two groups is significant (p = .02). Conclusion. In H. pylori–positive subjects with GERD, long‐term acid suppression leads to a shift from antral‐ to corpus‐predominant gastritis that can be prevented by prior eradication. The shift is accompanied by an increase in corpus atrophy. H. pylori infection should be eradicated prior to long‐term acid suppression with proton pump inhibitors.     

Impact of self-reported Gastroesophageal reflux disease in subjects from COPDGene cohort

Background

The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.

Methods

Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.

Results

GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.

Conclusions

In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.     

Omeprazole Blocks STAT6 Binding to the Eotaxin-3 Promoter in Eosinophilic Esophagitis Cells

Background

Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD) nevertheless can respond to proton pump inhibitors (PPIs), which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE). The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.

Methods/Findings

Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.

Conclusions/Significance

PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.     

Proton Pump Inhibitors and the Risk of Adverse Cardiac Events

Background

Recent evidence suggests that proton pump inhibitors (PPIs) might be linked with adverse cardiac events, but a causal relationship is unproven.

Methods

We applied the self-matched case series method to two studies using population-based health care data from Ontario, Canada between 1996 and 2008. The first included subjects aged 66 years or older hospitalized for acute myocardial infarction within 12 weeks following initiation of PPI, while the second included subjects hospitalized for heart failure. In both studies we designated the primary risk interval as the initial 4 weeks of therapy and the control interval as the final 4 weeks. To test the specificity of our findings we examined use of histamine H2 receptor antagonists and benzodiazepines, drugs with no plausible causal link to adverse cardiac events.

Results

During the 13-year study period, we identified 5550 hospital admissions for acute myocardial infarction and 6003 admissions for heart failure within 12 weeks of commencing PPI therapy. In the main analyses, we found that initiation of a PPI was associated with a higher risk of acute myocardial infarction (odds ratio 1.8; 95% confidence interval 1.7 to 1.9) and heart failure (odds ratio 1.8; 95% confidence interval 1.7 to 1.9). However, secondary analyses revealed similar risk estimates histamine H2 receptor antagonists and benzodiazepines, drugs with no known or suspected association with adverse cardiac events.

Conclusion

PPIs are associated with a short-term risk of adverse cardiac events, but similar associations are seen with other drugs exhibiting no known cardiac toxicity. Collectively these observations suggest that the association between PPIs and adverse cardiac events does not represent reflect cause-and-effect.     

Management of refractory and complicated reflux esophagitis.

Simple intermittent heartburn with minor or no esophagitis can be treated with simple measures including lifestyle changes and antacids as needed, or H2 receptor antagonists (H2RA), and has a good outcome. Problematic reflux includes resistance to therapy, stricture, Barrett''s esophagus and aspiration. Severe reflux esophagitis, often resistant to H2RA therapy, requires more potent treatment with potent acid suppression using proton pump inhibitors, often indefinitely. When complicated by stricture, dilatations with potent acid suppression are needed. Barrett''s esophagus is subject to esophagitis, which is no more difficult to treat than other cases of esophagitis. Reflux in Barrett''s esophagus should be treated on its own merits without regard to the presence of Barrett''s epithelium. Dysplasia leading to adenocarcinoma is a different problem, apparently not influenced by reduced exposure to acid. Indications for antireflux surgery are quite limited and should be carefully analyzed as a cost/risk/benefit problem.     

The H2-receptor antagonist era in duodenal ulcer disease.

This paper reviews the remarkable impact of H2-receptor antagonists on duodenal ulcer management. The development and the scientific rationale of these agents are presented, and efficacy and safety aspects in the short- and long-term treatment of duodenal ulcer disease discussed. Attention is focused on the possible role of "acid rebound" in ulcer relapse following the withdrawal of therapy and on the clinical relevance of prolonged suppression of acid secretion in patients on long-term therapy.     

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

Background and Aims

Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.

Methods

Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.

Results

In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H₂ blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.

Conclusions

Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.     

Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: A new biological vision

Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first‐line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD‐Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d‐ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms.     

终末期肾病患者合并胃食管反流病的临床研究进展

胃食管反流病(GERD)是最常见的食管疾病之一。多项研究表明,终末期肾病(ERSD)患者GERD的患病率高于普通人群。目前对于ERSD患者特别是血液透析患者GERD的症状特点及严重程度的研究较少。ESRD患者常并发或伴发糖尿病、高血压等,而糖尿病神经病变可影响胃排空功能,钙拮抗剂和硝酸酯类药物可影响LES舒张功能。透析相关淀粉样变通过影响食管蠕动、食管下段括约肌张力和胃排空影响GERD的发生。ERSD患者中,相当比例的患者全身状况不佳,行胃镜风险较高,常常应用标准化量表或质子泵抑制剂诊断试验评估患者症状性GERD患病情况。ESRD及透析患者GERD的知晓率仍较低,部分患者自行服用碳酸氢钠等非一线药物控制症状。理论上对于ESRD及透析患者伴随的GERD进行早期诊断和治疗可能提高患者生活质量,并减少水钠摄入,改善血压及透析间期体重增加,降低心血管事件风险,具体的临床获益仍有待进一步研究证实。     

Effects of Helicobacter pylori eradication on gastroesophageal reflux disease

Background and Aims: Helicobacter pylori infection appears to be a protective factor for gastroesophageal reflux disease (GERD). However, H. pylori is associated with the subtype of esophageal carcinoma, and long‐term proton‐pump inhibition usage would cause gastric atrophy in patients with persistent H. pylori infection, which is a precancerous lesion. The relationship between H. pylori infection and GERD is still unclear. We aimed to confirm whether the eradication of H. pylori would worsen or improve symptomatic or endoscopic GERD. Methods: A systematic review of the published data was undertaken, and a meta‐analysis was performed to determine the effect of H. pylori eradication on the occurrence of symptomatic (heartburn, acid regurgitation) and endoscopically proven erosive (esophagitis) GERD in patients with or without pre‐existing GERD. Results: A total of 11 articles met the inclusion criteria and thus were included in the meta‐analysis. There was no significant difference in the frequency of symptomatic or endoscopically proven erosive GERD after the eradication between patients with H. pylori eradicated and those with persistent infection, regardless of follow‐up period, location, or the baseline disease. Conclusion: H. pylori eradication does not aggravate the clinical outcomes in terms of short‐term and long‐term posteradication occurrence of GERD. There is no association between H. pylori eradication and the development of GERD in the patients with different diseases, even those with GERD.