Gastroesophageal Reflux Disease Phenotypes Research Articles

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Utility of the Post-Reflux Swallow-Induced Peristaltic Wave Index and Mean Nocturnal Baseline Impedance for the Diagnosis of Gastroesophageal Reflux Disease Phenotypes in Children.

(1) Objectives: Assessment of novel impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been proposed to enhance the accuracy of gastroesophageal reflux disease (GERD) diagnosis. We aimed to evaluate the clinical value of MNBI and the PSPW index in discerning different phenotypes of GERD in children. (2) Methods: We conducted a prospective, observational study that included 49 children aged 5-18 years, referred for MII-pH monitoring due to negative endoscopy and persisting gastroesophageal reflux symptoms despite acid-suppressant treatment. The PSPW index and MNBI were assessed along with conventional metrics. (3) Results: Using a receiver operating characteristic (ROC) curve analysis, MNBI (AUC 0.864) and the PSPW index (AUC 0.83) had very good performance in differentiating between non-erosive reflux disease (NERD) and functional phenotypes. The PSPW index (AUC 0.87) discriminated better between functional heartburn (FH) and reflux hypersensitivity (RH) compared to the MNBI (AUC 0.712). A PSPW cut-off value of 65% provided a sensitivity of 76.9% and a specificity of 90% in distinguishing FH and RH. The PSPW index (AUC 0.87) proved to have better performance than the MNBI (AUC 0.802) in differentiating between FH and non-FH patients. MNBI diagnosed FH with a sensitivity of 84% and a specificity of 80.6% at a cut-off value of 2563 Ω. (4) Conclusions: The PSPW index and MNBI are useful to distinguish between GERD phenotypes in pediatric patients.

The Utility of Novel pH-Impedance Monitoring Parameters (PSPW Index and MNBI) in Pediatric Gastroesophageal Reflux Disease Phenotypes-A Systematic Review.

Background/Objectives: Researchers have proposed two novel impedance-pH parameters, mean nocturnal baseline impedance (MNBI) and the post-reflux swallow-induced peristaltic wave (PSPW) index, to enhance the diagnosis of gastroesophageal reflux disease (GERD) and enable better predictions of the effectiveness of anti-reflux therapies. This systematic review aims to synthesize the available evidence on the utility of the PSPW index and MNBI as diagnostic tools for pediatric GERD. Methods: A systematic search of studies reporting PSPW index and MNBI values in patients with GERD was performed in PubMed, Embase, Clarivate, Scopus, Cochrane and Google Scholar databases from their beginning until April 2024. The following terms were used: GERD, children, pediatric, PSPW and MNBI. Results: Eight studies were included, describing 479 patients ranging from 2 months to 17 years old over an 8-year period in 12 pediatric centers. Four studies demonstrated that children with pathological acid exposure have a significantly lower MNBI, with a good discriminatory ability to diagnose GERD. The PSPW index showed lower values in patients with reflux hypersensitivity (RH) compared to those with functional heartburn (FH). Conclusions: Patients with pathological acid exposure tend to exhibit lower MNBI and PSPW index values compared to those with normal acid exposure. MNBI and the PSPW index show promise as diagnostic tools in distinguishing between different GERD phenotypes. Further research is needed to establish standardized diagnostic criteria and optimize the clinical applicability in GERD diagnosis and management.

Phenotypes of gastroesophageal reflux disease: a vision based on its pathophysiology

Phenotypes of gastroesophageal reflux disease: a vision based on its pathophysiology

The role of hypervigilance in chronic esophageal diseases: a scoping review.

Hypervigilance has emerged as an important construct in esophageal symptom reporting, but a review of the literature does not currently exist. This scoping review aimed to generate a comprehensive overview of the literature on hypervigilance in esophageal diseases and summarize the evidence for each esophageal disease. Guided by the Joanna Briggs Institute scoping review methodology, articles that were peer-reviewed original studies, published in English, and included adult patients with at least one esophageal disease were included. Articles were retrieved from PubMed and Embase databases and screened first by title and abstract for an initial round of exclusions, and then again by full text for a second round of exclusions. Nineteen studies were included. Studies were categorized by primary diagnosis: achalasia (1, 5%), eosinophilic esophagitis (1, 5%), gastroesophageal reflux disease (GERD) (6, 32%), laryngopharyngeal reflux (3, 16%), non-cardiac chest pain (3, 16%), and multi-disorder samples (5, 26%). Studies primarily evaluated associations between hypervigilance and symptom severity, psychosocial functioning, health-related quality of life, and physiological disease variables. A number of studies also evaluated hypervigilance across esophageal diseases or presentations (e.g., across motility disorders, across GERD phenotypes). The role of hypervigilance in symptom reporting has been investigated in multiple esophageal conditions. Findings suggest potential clinical utility in assessing hypervigilance, such as for disease conceptualization and treatment planning. Future research is needed in larger samples, with consistent measures of hypervigilance, and using data synthesis methodology (i.e., systematic reviews) to better compare and contrast findings across studies.

Association between Mean Nocturnal Baseline Impedance (MNBI) and Post-Reflux Swallow-Induced Peristaltic Wave Index (PSPW) in GERD Patients.

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders in the world. Two parameters, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW), have been recently proposed to help differentiate GERD phenotypes. Our study aimed to assess whether there is any correlation between the two parameters, while also taking a look at their ability to distinguish between GERD phenotypes. We recruited 81 patients who were divided into 4 groups based on their GERD phenotype: erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Both MNBI (AUROC 0.855) and PSPW (AUROC 0.835) had very good performances in separating ERD patients from non-ERD patients. PSPW (AUROC 0.784) was superior to MNBI (AUROC 0.703) in distinguishing NERD patients from patients with RH or FH. The PSPW index (AUROC 0.762) was more effective than MNBI (AUROC 0.668) in separating RH from FH. We found that PSPW and MNBI have a strong statistical correlation (Pearson correlation coefficient, r = 0.722, p < 0.001). Furthermore, PSPW predicted pathological MNBI (<2292 Ω) with good performance (AUROC 0.807). MNBI and PSPW are useful in distinguishing GERD phenotypes, with a strong correlation between the two parameters.

Roles of swallowing and belching in different phenotypes of gastroesophageal reflux disease.

The contributions of swallowing and belching to specific gastroesophageal reflux disease (GERD) phenotypes are unclear. This study retrospectively analyzed esophageal pH/impedance studies, comparing reflux events preceded by gastric belching (GB), supragastric belching (SGB), air swallowing, and liquid/solid swallowing based on reflux position, lower esophageal sphincter (LES) pressure, and acid exposure time (AET). 20 GERD patients and 10 controls were studied. Upright GERD patients and controls had a higher proportion of reflux events with a preceding swallow or belch (0.64, 0.64) than the supine group (0.38, p = 0.043). The upright group and controls trended toward a higher proportion of reflux events preceded by overall swallowing (0.61, 0.50) and air swallowing (0.55, 0.48) than the supine group (0.32, 0.31 p = 0.064, p = 0.11), but the three groups had similar rates of liquid/solid swallowing (0.032, 0.024, 0.017, p = 0.69). LES pressure did not correlate with reflux events preceded by swallowing (R2 = 0.021, p = 0.44). There was a higher rate of events preceded by gastric belching in the control group (0.14) than in the upright (0.032) and supine groups (0.066, p = 0.049). LES pressure did not correlate with the rate of events preceded by belching (R2 = 0.000093, p = 0.96). Normal AET patients had a higher rate of events preceded by GB (0.12) than those with increased acid exposure (0.030, p = 0.0083), but the two groups had similar rates of preceding air (0.43, 0.47, p = 0.68), liquid/solid (0.018, 0.032, p = 0.30), and overall swallowing (0.44, 0.53, p = 0.38). Swallowing more than belching is a dominant mechanism for reflux irrespective of GERD position, LES pressure, and AET.

Real-world Prescription Patterns and Patient Satisfaction Regarding Maintenance Therapy of Gastroesophageal Reflux Disease: An Observational, Cross-sectional, Multicenter Study.

Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

S471 Roles of Swallowing and Belching in Different Phenotypes of Gastroesophageal Reflux Disease

S471 Roles of Swallowing and Belching in Different Phenotypes of Gastroesophageal Reflux Disease

The Role of Distal Mean Nocturnal Baseline Impedance in Differentiating GERD Phenotypes.

Gastroesophageal reflux disease (GERD) is one of the most frequent digestive pathologies. The current diagnosis of GERD either by trial of proton pump inhibitors (PPIs), endoscopy or by multichannel impedance pH study (MII/pH) has limitations. Our study aims to show if mean nocturnal baseline impedance (MNBI) can differentiate between the GERD phenotypes. We recruited 62 patients who underwent upper digestive endoscopy and MII/pH, with some patients undergoing esophageal manometry to exclude motility disorders. Patients were separated into 4 GERD phenotypes: erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH). Proximal MNBI was calculated as the mean value of the proximal 2 channels (Z1 and Z2), and distal MNBI was calculated as the mean value of the distal 4 channels (Z3, Z4, Z5, Z6). Distal MNBI can help distinguish the abnormal acid exposure time (AET) phenotypes (ERD, NERD) from normal AET phenotypes (RH, FH) with a decent performance (AUROC 0.857). Distal MNBI has good accuracy in separating ERD from other phenotypes (AUROC 0.872). Furthermore, distal MNBI can differentiate FH from ERD, NERD, RH with good accuracy (AUROC 0.879), and on top of that is able to separate FH from RH (AUROC 0.817). Our study showed that distal MNBI is a good method of differentiating GERD phenotypes and should be taken into consideration in future studies to assess its validity in helping physicians make the correct diagnosis.

Fenotipos de la enfermedad por reflujo gastroesofágico: una visión basada en su fisiopatología.

The advancement of knowledge in pathophysiology and underlying etiologies of gastroesophageal reflux disease (GERD) has allowed the development of the concept of disease beyond the acidity of reflux. The variability in the symptom presentation and the response to treatment cannot be attributed only to reflux composition, since esophageal factors, such as structural, mechanical, biochemical, and physiological aspects, play an important role. The proposed personalized approach to GERD uses a stepwise approach that optimizes performance and phenotypic outcome while minimizing invasiveness, risk, and cost. Throughout the staggered approach to determine the GERD phenotype, clinicians may choose to stop further testing and continue treatment if available information identifies a different GERD phenotype. Since not all phenotypes GERD are the same and not all treatments are appropriate for all patients, therapeutic strategies must be personalized according to their phenotype.

Computer-Based Intelligent Solutions for the Diagnosis of Gastroesophageal Reflux Disease Phenotypes and Chicago Classification 3.0.

Gastroesophageal reflux disease (GERD) is a multidisciplinary disease; therefore, when treating GERD, a large amount of data needs to be monitored and managed.The aim of our study was to develop a novel automation and decision support system for GERD, primarily to automatically determine GERD and its Chicago Classification 3.0 (CC 3.0) phenotypes. However, phenotyping is prone to errors and is not a strategy widely known by physicians, yet it is very important in patient treatment. In our study, the GERD phenotype algorithm was tested on a dataset with 2052 patients and the CC 3.0 algorithm was tested on a dataset with 133 patients. Based on these two algorithms, a system was developed with an artificial intelligence model for distinguishing four phenotypes per patient. When a physician makes a wrong phenotyping decision, the system warns them and provides the correct phenotype. An accuracy of 100% was obtained for both GERD phenotyping and CC 3.0 in these tests. Finally, since the transition to using this developed system in 2017, the annual number of cured patients, around 400 before, has increased to 800. Automatic phenotyping provides convenience in patient care, diagnosis, and treatment management. Thus, the developed system can substantially improve the performance of physicians.

Acid exposure time better predicts outcomes following anti-reflux surgery than DeMeester score.

Criteria to diagnose gastroesophageal reflux disease (GERD) vary. The American Gastroenterology Association (AGA) 2022 Expert Review on GERD focuses on acid exposure time (AET) rather than DeMeester score from ambulatory pH testing (BRAVO). We aim to review outcomes following anti-reflux surgery (ARS) at our institution, grouped by differing criteria for the diagnosis of GERD. A retrospective review of a prospective gastroesophageal quality database was performed for all patients undergoing evaluation for ARS with preoperative BRAVO ≥ 48h. Group comparisons were made using two-tailed Wilcoxon rank-sum and Fisher's exact tests and two-tailed statistical significance of p < 0.05. Between 2010 and 2022, 253 patients underwent an evaluation for ARS with BRAVO testing. Most patients (86.9%) met our institution's historical criteria: LA C/D esophagitis, Barrett's, or DeMeester ≥ 14.72 on 1+ days. Fewer patients (67.2%) met new AGA criteria: LA B/C/D esophagitis, Barrett's, or AET ≥ 6% on 2+ days. Sixty-one patients (24%) met historical criteria only, with significantly lower BMI, ASA, less hiatal hernias, and less DeMeester and AET-positive days, a less severe GERD phenotype. There were no differences between groups in perioperative outcomes or % symptom resolution. Objective GERD outcomes (need for dilation, esophagitis, and postop BRAVO) were equivalent between groups. Patient-reported quality of life scores, including GERD-HRQL, RSI, and Dysphagia Score did not differ between groups from preop through 1year postop. Those who met our historical criteria only reported significantly worse RSI scores (p = 0.03) and worse GERD-HRQL scores at 2years postop, though not statistically significant (p = 0.07). Updated AGA GERD guidelines exclude a portion of patients who historically would have been diagnosed with and surgically treated for GERD. This cohort appears to have a less severe GERD phenotype but equivalent outcomes up to 1year, with more atypical GERD symptoms at 2years postop. AET may better define who should be offered ARS than DeMeester score.

Sensory Phenotype of the Oesophageal Mucosa in Gastro-Oesophageal Reflux Disease.

Gastroesophageal reflux disease (GORD) affects up to 20% of Western populations, yet sensory mechanisms underlying heartburn pathogenesis remain incompletely understood. While central mechanisms of heartburn perception have been established in earlier studies, recent studies have highlighted an important role of neurochemical, inflammatory, and cellular changes occurring in the oesophageal mucosa itself. The localization and neurochemical characterisation of sensory afferent nerve endings differ among GORD phenotypes, and could explain symptom heterogeneity among patients who are exposed to similar levels of reflux. Acid-induced stimulation of nociceptors on pain-sensing nerve endings can regulate afferent signal transmission. This review considers the role of peripheral mechanisms of sensitization in the amplification of oesophageal sensitivity in patients with GORD.

Esophageal Reflux Hypersensitivity: A Comprehensive Review.

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts' consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

Esophageal secondary peristalsis following acid infusion and chemical clearance correlate with mucosal integrity and acid sensitivity in GERD patients.

Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. This was an investigator-initiated, prospective, cross-sectional study. Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007). In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study

BackgroundConflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. Methods338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. Results45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. ConclusionsNERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.

Phenotypes of gastroesophageal reflux disease: classification, pathogenesis and diagnostic criteria: A review

The literature review focuses on the current understanding of visceral hypersensitivity mechanisms in the esophagus. Mechanisms of peripheral and central sensitization and their relation to heartburn symptoms are covered in detail. Diagnostic criteria and algorithms for non-erosive reflux disease, functional heartburn, and esophagus hypersensitivity based on pH-impedance testing and high-resolution esophageal manometry data are presented.

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.

GASTROESOPHAGEAL REFLUX DISEASE

Gastroesophageal reflux disease (GERD) is a chronic disease usually caused by the reflux of acidic gastric and duodenal contents into the distal esophagus. Major symptoms of GERD are acidity, heartburn, acid regurgitation, and chest pain. It is a digestive disease with the direct medical costs estimated around 9.3 billion dollars annually, and with the symptoms portending a low quality of life. The most common and known phenotype of GERD is Reflux esophagitis (RE). Many countries has a high prevalence of GERD, Especially in USA, about 44% of Americans suffer from GERD symptoms at least once monthly, 17% once weekly, and 7% once daily. Traditionally, GERD is less common in Asians. The overall prevalence of RE in Japanese adults is about 16%. Aging causes various physiologic changes in GIT that may increase the risk of developing complications such as GERD. Age-related changes in the physiology of the esophagus can be divided into two categories: motility and sensory. In general, changes in esophageal motility are mild and tend to be quiet in an older patient. It is possible that both the motility and nerve changes observed in the esophagus of older patients, combined with lower comorbidities and medication use, lead to a higher risk of esophageal mucosa to reflux and cause inflammation and development of GERD-related problems. Previously, it was thought that gastric acid release decreased with age, but further research revealed that the underlying mechanism may have been Helicobacter pylori infection that eventually developed atrophic gastritis. As the prevalence of Helicobacter pylori infection has decreased over the last 3-4 decades, more recent studies have shown that gastric acid secretion is maintained normally in more than 80% of elderly subjects. Comorbidity and commonly used drugs can reduce esophageal sphincter tone, esophageal clearance mechanisms, and saliva production.&#x0D; A low-fat diet likely contributes to a more favorable stomach distribution. Male gender, civil servant, smoking, strong tea, alcohol consumption, meat diet and body mass index (BMI) are risk factors associated with GERD. In many countries, dietary fat, cholesterol, saturated fatty acid (SFA), dietary fiber, and other nutrients are associated with GERD. An epidemiological study showed a link between high fat intake and GERD. Also, dietary fiber, particularly cereal fiber, has been found to reduce the risk of adenocarcinoma of the esophagus and stomach, of which GERD is a well-known risk factor. The mechanism may be that dietary fiber reduces the intake of gastric nitrites, which is thought to promote reflux by relaxing the lower esophageal sphincter (LES). A high-fiber diet has played a protective role in GERD. However, dietary fiber reduced the number of gastroesophageal refluxes, but increased their duration, and had no significant effect on gastric emptying and gastric acid secretion. Diet plays an important role in controlling acid reflux symptoms and is the first line of treatment used for people with GERD. Foods high in fiber make you feel full, so you're less likely to overeat, which can contribute to heartburn. So get healthy fiber from these foods, such as whole grains like oatmeal, couscous, and brown rice, root vegetables like sweet potatoes, carrots, and beets, and green vegetables like asparagus, broccoli, and green beans. Lemon juice is generally considered very acidic, but a small amount of lemon juice mixed with warm water and honey has an alkalizing effect, neutralizing stomach acid. In addition, honey has natural antioxidants that protect the health of cells. On the other hand, Ginger is another top digestive aid due to its medicinal properties. It is alkaline in nature and anti-inflammatory, which eases irritation in the digestive tract. Try sipping ginger tea whenever you feel heartburn. The goal is to create a diet based on a healthy variety of foods, including fruits and vegetables, lean protein sources, complex carbohydrates, and healthy fats. If you suspect that food may be triggering or worsening your GERD symptoms, try keeping a daily, weekly diary.