OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Network Pharmacology ; Data Mining ; Gastroesophageal Reflux/drug therapy*

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 16S 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-PPI-user 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 short-term 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.
Adult ; Aged ; Bacteria ; genetics ; isolation & purification ; Feces ; microbiology ; Female ; Gastric Mucosa ; microbiology ; Gastroesophageal Reflux ; drug therapy ; microbiology ; Gastrointestinal Microbiome ; drug effects ; Humans ; Male ; Microbiota ; Middle Aged ; Proton Pump Inhibitors ; therapeutic use ; RNA, Ribosomal, 16S ; genetics

BACKGROUND/AIMS: Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized form of eosinophilic esophagitis (EoE) that responds to PPI therapy. It remains unclear whether PPI-REE represents a subphenotype of gastroesophageal reflux disease, a subphenotype of EoE, or its own distinct entity. The aim was to evaluate the clinicopathologic features of PPI-REE. METHODS: Six patients were diagnosed with PPI-REE based on symptoms, endoscopic abnormalities, esophageal eosinophilia with > or =15 eosinophils/high-power field, and a response to PPI treatment. Symptoms and endoscopic and pathological findings were evaluated. RESULTS: The median follow-up duration was 12 months. Presenting symptoms included dysphagia, heartburn, chest pain, foreign body sensation, acid reflux, and sore throat. All patients had typical endoscopic findings of EoE such as esophageal rings, linear furrows, nodularity, and whitish plaques. Three patients had a concomitant allergic disorder, and one had reflux esophagitis. Four patients exhibited elevated serum IgE, and five had positive skin prick tests. All patients experienced symptomatic resolution within 4 weeks and histologic resolution within 8 weeks after starting PPI therapy. There was no symptomatic recurrence. CONCLUSIONS: PPI therapy induced rapid resolution of symptoms and eosinophil counts in patients with PPI-REE. Large-scale studies with long-term follow-up are warranted.
Adult ; Asian Continental Ancestry Group ; Chest Pain/etiology ; Deglutition Disorders/etiology ; Diagnosis, Differential ; Eosinophilic Esophagitis/complications/*drug therapy/*pathology ; Esophagus/pathology ; Female ; Follow-Up Studies ; Gastroesophageal Reflux/etiology ; Heartburn/etiology ; Humans ; Male ; Middle Aged ; Pharyngitis/etiology ; Phenotype ; Proton Pump Inhibitors/*therapeutic use ; Republic of Korea ; Retrospective Studies ; Sensation Disorders/etiology ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease, with eosinophilic infiltration limited to the esophagus. A minority of EoE patients respond well to proton pump inhibitor (PPI) therapy alone, and that condition is labelled PPI-responsive esophageal eosinophilia (PPI-REE). The prevalence of PPI-REE among EoE cases is unknown. We aimed to identify clinical manifestations of PPI-REE, and the proportion of PPI-REE among all EoE cases. METHODS: We reviewed pathology of the 4,075 patients who underwent esophageal biopsy at an institution from March 2003 to July 2015. EoE was diagnosed based on esophageal symptoms and eosinophilic infiltration limited to the esophagus, with ≥15 eosinophils per high-power field. We collected endoscopic and pathologic findings, and clinical features for these patients. RESULTS: Thirteen (0.3%) patients were diagnosed with EoE. Clinical manifestations were dysphagia (30.8%), foreign body sensation (23.1%), regurgitation (23.1%), cough (15.4%), heartburn (15.4%), nausea (7.7%), dyspepsia (7.7%). The endoscopic findings noted were polypoid lesion (23.1%), whitish plaque or exudate (23.1%), linear furrow (7.7%), concentric ring (7.7%), nodularity (7.7%), erosion (7.7%), and normal (30.8%). Of these patients, five had a favorable course with PPI as monotherapy. CONCLUSIONS: The proportion of EoE among all patients undergoing endoscopic biopsy was 0.3%. Of those, PPI-REE comprised 38%. Most of the endoscopic findings were atypical or normal when compared to the typical findings in EoE. In conclusion, patients who present with symptoms related to esophageal dysfunction need esophageal biopsy, regardless of the endoscopic findings. Moreover, patients diagnosed with EoE need to be treated first with PPI alone.
Adult ; Aged ; Endoscopy, Gastrointestinal ; Eosinophilic Esophagitis/*diagnosis/etiology ; Esophagus/pathology ; Female ; Gastroesophageal Reflux/drug therapy ; Hospitals, University ; Humans ; Male ; Middle Aged ; Proton Pump Inhibitors/*adverse effects/therapeutic use ; Retrospective Studies

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.
Chest Pain ; etiology ; Esophagus ; drug effects ; Gastroenterology ; methods ; Gastroesophageal Reflux ; diagnosis ; drug therapy ; Heartburn ; diagnosis ; drug therapy ; Humans ; Hydrogen-Ion Concentration ; Life Style ; Primary Health Care ; Proton Pump Inhibitors ; therapeutic use ; Surveys and Questionnaires

The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.
Anti-Ulcer Agents/therapeutic use ; Cytochrome P-450 CYP2C19/genetics ; Esophageal pH Monitoring ; Gastroesophageal Reflux/drug therapy/metabolism/*pathology ; Genotype ; Heartburn ; Humans ; Proton Pump Inhibitors/therapeutic use

BACKGROUNDHelicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy.

METHODSPatients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The χ2 test and t-test were used, respectively, for enumeration and measurement data.

RESULTSThere were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546).

CONCLUSIONSBased on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Adolescent ; Adult ; Aged ; Amoxicillin ; therapeutic use ; Esomeprazole ; therapeutic use ; Esophagitis, Peptic ; drug therapy ; etiology ; microbiology ; Female ; Gastroesophageal Reflux ; drug therapy ; etiology ; microbiology ; Helicobacter Infections ; complications ; drug therapy ; Helicobacter pylori ; drug effects ; pathogenicity ; Humans ; Male ; Middle Aged ; Tinidazole ; therapeutic use ; Young Adult

BACKGROUND/AIMS: Globus is a persistent or intermittent non-painful sensation of a lump or foreign body in the throat and a commonly encountered clinical condition. We aim to evaluate the prevalence of gastroesophageal reflux disease (GERD) and to determine the parameters for predicting the response to treatment with proton pump inhibitor (PPI) using wireless pH monitoring in patients with globus sense. METHODS: We retrospectively reviewed the medical records of 37 patients with atypical GERD symptoms. A total of 27 patients with dominant globus sense were enrolled. Endoscopic examination and 48-hour wireless esophageal pH monitoring were performed, and the patients underwent a therapeutic trial of full dose PPIs daily over a period of 4 weeks. RESULTS: Both typical and atypical GERD symptoms co-existed in 14 patients (51.9%, 14/27). According to ROME III criteria, 19 patients (70.4%, 19/27) were diagnosed as GERD. Twelve patients (44.4%, 12/27) were PPI responders. A significant difference in the frequency of symptom index (+) or symptom associated probability (+) was observed between the PPI responder group and the non-responder group (p<0.01). CONCLUSIONS: In patients with globus sense, 70.4% were diagnosed with GERD. Symptom index/symptom associated probability in wireless ambulatory pH monitoring was a good objective parameter for PPI responder.
Adult ; Aged ; Case-Control Studies ; Endoscopy, Digestive System ; Esophageal pH Monitoring ; Female ; Gastroesophageal Reflux/*diagnosis/drug therapy/pathology ; Humans ; Male ; Manometry ; Middle Aged ; Proton Pump Inhibitors/therapeutic use ; Retrospective Studies ; Severity of Illness Index ; Wireless Technology

Noncardiac chest pain (NCCP) is defined as recurring, angina-like, retrosternal chest pain of noncardiac origin. Although patients with NCCP have excellent long-term prognosis, most suffer persistently from their symptoms. Several pathophysiological mechanisms have been suggested, including gastroesophageal reflux disease (GERD), esophageal motility disorder, esophageal hypersensitivity, and psychological comorbidity. Among them, GERD is the most common cause of NCCP. Therefore, GERD should first be considered as the underlying cause of symptoms in patients with NCCP. Empirical proton pump inhibitor (PPI) treatment with a preferably double dose for more than 2 months could be cost-effective. PPI test can also be used for diagnosis of GERD-related NCCP, but it should be considered for patients with NCCP occurring at least weekly and its duration should be at least 2 weeks. However, upper endoscopy and esophageal pH monitoring are necessary when the diagnosis of GERD is uncertain. Esophageal impedance-pH monitoring could further improve the diagnostic yield. Patients with GERD-related NCCP should preferably be treated with a double dose PPI until symptoms remit (may require more than 2 months of therapy for optimal symptom control), followed by dose tapering to determine the lowest PPI dose that can control symptoms. However, treatment of patients with non-GERD-related NCCP is challenging. An empirical treatment of antidepressants could be considered. If there are specific esophageal motility disorders, smooth muscle relaxants or endoscopic treatment may be considered in selected cases. If none of these traditional treatments is effective, a psychology consultation for cognitive behavioral therapy should be considered.
Chest Pain/*diagnosis/etiology ; Esophageal pH Monitoring ; Gastroesophageal Reflux/complications/*diagnosis/drug therapy ; Humans ; Manometry ; Proton Pump Inhibitors/therapeutic use

OBJECTIVE: To explore the mechanism, clinical characterization, diagnosis and therapeutic approach of vocal process granuloma(VPG) induced by gastroesophageal reflux. METHOD: We performed a retrospective review of 4 cases. RESULT: In 4 male cases, 3 cases had no obvious symptoms of stomach and esophagus and 1 case had symptoms of bloating and acid reflux. Additionally, 4 cases in which lesions were all located to the left side were diagnosed by trial therapy with proton pump inhibitors (PPIs) with good responding. 2 of 4 cases were relapsed after operations. Meanwhile 4 patients were treated by Rabeprazole for acid suppression therapy and 3 cases were cured and 1 invalid case was cured by Pantoprazole. All patients were followed up for 4-48 months with no recurrence. CONCLUSION Gastroesophageal reflux is an important pathogenic factor to the VPG. The majority of patients with VPG do not have gastroesophageal reflux symptoms. Besides, most lesions located in the left are associated with sleeping position. The diagnosis is mainly based on the laryngoscope examination and trial of acid suppression therapy. Moreover, recurrence risk is high-with simple operation in VPG therefore the main treatment is a antireflux and it is also valid by replacing byother PPI treatment. The treatment must be long enough. Meanwhile, the comprehensive treatment should be noticed.
2-Pyridinylmethylsulfinylbenzimidazoles ; therapeutic use ; Arytenoid Cartilage ; pathology ; Gastroesophageal Reflux ; complications ; drug therapy ; Granuloma ; etiology ; Humans ; Male ; Pantoprazole ; Proton Pump Inhibitors ; therapeutic use ; Retrospective Studies ; Treatment Outcome