Esophageal Dysmotility and Gastroesophageal Reflux Disease Risk in Hypermobile Ehlers-Danlos Syndrome.

Patients with troublesome reflux‑like symptoms, in whom routine empirical proton pump inhibitor (PPI) therapy is often unsatisfactory, present a therapeutic challenge and are frequently referred for gastroenterological evaluation to confirm a diagnosis of gastroesophageal reflux disease (GERD). We aimed to determine the prevalence of objectively confirmed GERD (diagnosed according to the Lyon Consensus 2.0 criteria) in patients with typical and / or atypical troublesome reflux‑like symptoms who did not respond or partially responded to PPI therapy, and were referred for esophageal pH‑impedance monitoring. This was a retrospective study analyzing pH‑impedance monitoring results of 500 patients who previously underwent endoscopy. A conclusive GERD diagnosis was defined as an acid exposure time (AET) greater than 6%, or 4%-6% with supporting evidence (number of reflux episodes >80/d, and / or mean nocturnal basal impedance <1500 Ω, and / or a positive reflux-symptom association). Of the 500 patients analyzed, 477 reported symptoms, which were categorized as follows: isolated typical (n = 49; 10.3%), both typical and atypical (n = 206; 43.2%), and isolated atypical (n = 222; 46.5%). AET greater than 6% was found in 12 (24.5%), 41 (19.9%), and 27 patients (12.2%) in each group, respectively. The inclusion of supportive evidence for patients with AET of 4%-6% increased the number of GERD diagnoses in each group to 23 (46.9%), 68 (33%), and 40 (18%), respectively. When endoscopy findings were factored in, the prevalence of GERD in the whole study population increased from 27% (n = 135) to 29.6% (n = 148). Among the 161 individuals reporting heartburn, 41.6% met the criteria of functional heartburn. Only 29.6% of the patients referred for GERD evaluation fulfilled the objective diagnostic criteria for the disease. GERD was present in about half of the patients with isolated typical symptoms,one‑third of those with both typical and atypical symptoms, and fewer than one‑fifth of those with isolated atypical symptoms.

Gastroesophageal reflux disease (GERD) is a chronic condition encompassing visceral pain-experienced as heartburn and, in some cases, inflammation of the esophageal mucosa. Although mast cell dysregulation has been described in disorders of gut-brain interaction, it has been understudied in GERD. We aimed to characterize mast cell localization and degranulation in GERD esophageal mucosa. Distal esophageal biopsies were collected from healthy control subjects (HC; n = 10) and subjects with functional heartburn (FH; n = 9), nonerosive reflux disease (NERD; n = 13), and erosive reflux disease (ERD; n = 12). Immunohistochemistry was used to visualize tryptase expression in the esophageal mucosa. The localization of tryptase+ mast cells was identified as intraepithelial or papillary, and the degranulation state of individual mast cells was determined based on the tryptase staining pattern. There was an increased density of mast cells in the esophageal papillae and epithelium of patients with ERD compared with HCs. The density of degranulated intraepithelial mast cells was significantly higher in subjects with FH and subjects with ERD compared with HCs, with a trend toward an increase in NERD. In NERD and ERD, the density of degranulated mast cells in papillae was significantly higher than in HCs. In FH, the density of intraepithelial mast cells positively correlated with reflux disease questionnaire (RDQ) score. Mast cells are more numerous in the esophageal mucosa of subjects with ERD, and activity is increased in subjects with FH, NERD, and ERD. This could contribute to mucosal inflammation, barrier dysfunction, and visceral hypersensitivity in patients with GERD. Future studies should investigate the role of mucosal mast cells in GERD, representing a possible future treatment target.NEW & NOTEWORTHY This is the first study to characterize mast cell localization and degranulation in subjects with pH-phenotyped FH, NERD, and ERD compared with healthy controls, showing elevated mast cell numbers in ERD, with increased degranulation in all patient groups (FH, NERD, and ERD). These findings suggest that mast cell activation may contribute to mucosal inflammation and symptom generation in GERD, particularly FH.

The primary objective of this study was to investigate the established correlations between psychological factors (anxiety, depression, and sleep quality) and esophageal physiological parameters. Additionally, this research aimed to examine the distribution patterns of these psychological factors across distinct subgroups of GERD symptom presentations. Retrospective analysis included 75 patients aged 18-70 with persistent reflux symptoms despite 8 weeks of proton pump inhibitor (PPI) therapy. Evaluations included esophagogastroduodenoscopy, high-resolution manometry, 24-hour pH-impedance monitoring, and psychological assessments (SAS, SDS, PSQI). Patients were grouped into refractory gastro-esophageal reflux disease (rGERD), functional heartburn (FH), and reflux hypersensitivity (RH). MNBI, PSPW-I, and EGJ-CI were compared, and correlations with psychological and sleep parameters were analyzed. Distal MNBI was significantly lower in rGERD (1177.91 ± 707.22 Ω) vs. FH (1995.77 ± 476.02 Ω) and RH (2062.35 ± 509.93 Ω) (P < 0.001). Anxiety prevalence was 85.7% in rGERD, 64.7% in FH, and 67.5% in RH (P = 0.302); depression affected 78.6% of rGERD, 70.8% of FH, and 72.9% of RH patients (P = 0.942). Poor sleep quality was present in > 80% of all groups. PSPW-I negatively correlated with anxiety (r = -0.181, P < 0.05) and depression (r = -0.158, P < 0.05), as did proximal MNBI with depression (r = -0.175, P < 0.05). A distal MNBI cutoff of 1531 Ω distinguished rGERD from FH/RH with 71.4% sensitivity and 87.5% specificity (AUC = 0.80). Anxiety, depression and poor sleep quality may reduce the efficacy of PPI. Distal MNBI effectively differentiates rGERD from FH/RH.

Functional heartburn (FH) is typically diagnosed by 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring; however, relying solely on 24-hour MII-pH may miss gastroesophageal reflux events due to day-to-day variability. In addition, since FH is a diagnosis of exclusion, other underlying conditions may be undiagnosed. This study aimed to assess the clinical course of FH and identify potential alternative diagnoses. Patients with heartburn refractory to proton pump inhibitors or potassium-competitive acid blockers who underwent endoscopy, high-resolution manometry, and MII-pH monitoring after discontinuation of acid-suppressive therapy and met diagnostic criteria for FH were retrospectively analyzed. Symptom severity was assessed using the frequency scale for the symptoms of GERD. Of 114 patients with refractory heartburn, 46 (40.4%) were diagnosed with FH. Of them, 42 patients were included in the analysis. During a mean follow-up of 18.1months, six patients underwent hypopharyngeal impedance-pH monitoring, and four were diagnosed with laryngopharyngeal reflux disease; one of them underwent laparoscopic anti-reflux surgery, resulting in symptomatic improvement. Additionally, one patient each was diagnosed with unstable angina, atlantoaxial subluxation, major depressive disorder, bipolar disorder, and somatoform disorder. Patients with unstable angina and atlantoaxial subluxation underwent the treatment of underlying conditions and had complete resolution of symptoms. Approximately 20% of patients initially diagnosed with FH were subsequently found to have alternative diagnoses. One-time, conventional 24-hour MII-pH testing may not be accurate to diagnose FH. Therefore, even after the initial diagnosis of FH, a meticulous long-term follow-up remains essential to identify initially unrecognized conditions.

Refractory reflux-like symptoms (rRLS) are frequently encountered in clinical practice and often reflect heterogeneous underlying mechanisms beyond acid exposure alone. Esophageal mucosal impedance has emerged as a marker of mucosal integrity, yet its role in phenotyping rRLS remains incompletely defined. In this retrospective study, adult patients with reflux-like symptoms who underwent multichannel intraluminal impedance-pH monitoring and high-resolution manometry were enrolled. Patients exhibiting persistent reflux-like symptoms despite ≥ 8 weeks of double-dose PPI therapy were defined as having rRLS. Baseline impedance (BI) and mean nocturnal baseline impedance (MNBI) were assessed at three esophageal levels, with particular focus on the mid-esophagus (9cm above the lower esophageal sphincter). Among patients with refractory symptoms, final diagnoses were established using clinical evaluation, endoscopy, impedance-pH monitoring, and manometry, allowing classification into refractory gastroesophageal reflux disease (GERD), functional heartburn/reflux hypersensitivity (FH/FES) and esophageal structural or functional abnormalities (ESFA). Among 165 patients, 73 (44.2%) exhibited rRLS. BI at the mid-esophageal level was significantly lower in refractory compared with non-refractory patients, whereas impedance values at proximal and distal levels showed no significant differences. In refractory patients, MNBI at the mid-esophagus differed significantly across diagnostic phenotypes. Lower MNBI values were associated with esophageal structural or functional abnormalities, while higher values were more frequently observed in functional heartburn or reflux hypersensitivity. Mid-esophageal mucosal impedance reflects impairment of mucosal integrity and may contribute to the physiological phenotyping of patients with rRLS. Location-specific impedance assessment could serve as a complementary tool to conventional reflux testing, aiding in mechanism-based classification. However, it should not be used in isolation to guide therapeutic decisions.

Abstract Background Proton pump inhibitors (PPI) are one of the most prescribed class of drugs in Canada. The high prevalence of PPI use is associated with the empiric treatment of gastroesophageal reflux disease (GERD) symptoms. However, not all patients with typical GERD symptoms have pathologic reflux of acid. The presence of esophageal mucosal injury and/or inappropriately elevated acid exposure time helps differentiate GERD from functional heartburn, where symptoms occur without pathological reflux. Continuing PPI therapy in patients without pathologic GERD provides minimal benefit and may expose these individuals to unnecessary risks, including nutrient deficiencies, increased susceptibility to gastrointestinal infections, and kidney injury. Deprescribing empiric PPI therapy, therefore, is an important step in managing patients found to not have GERD. Aims The goal of this study was to assess what percentage of patients referred to Kingston Health Sciences Center (KHSC) with suspected GERD on empiric PPI therapy have their PPI discontinued following normal endoscopic and acid reflux monitoring studies. Methods A retrospective cross-sectional study was conducted. Participants were adult patients with suspected GERD on PPI therapy who were referred to KHSC between January 2023 and December 2024 for 24h ambulatory pH studies following normal endoscopy studies conducted off PPI therapy. Patients that successfully completed the 24h ambulatory pH studies off PPI therapy were diagnosed with GERD or not. The primary outcome was PPI use following disclosure of the pH study results to patients. Continued PPI use was determined by a combination of chart review and patient interviews. Results A total of 56 patients with suspected GERD on empiric PPI therapy that were referred to KHSC from January 2023 and December 2024 were identified for having completed both endoscopy and acid reflux monitoring while off PPI therapy. Of the 56 patients, 49 patients had their PPI use determined either by documentation on their medical charts and/or by telephone interview. A total of 35 patients had normal endoscopy and normal esophageal acid monitoring; of these, 21 (60%) remained on PPI therapy. This contrasted with 13 of 14 patients (93%) who remained on PPI therapy after being diagnosed with GERD due to abnormal 24h pH studies. Conclusions Patients often remain on PPI therapy for reflux even when diagnostic investigations provide no supportive evidence of GERD. Given that PPI therapy is not benign and patient compliance appears high, it is important that physicians actively deprescribe PPI therapy in patients without evidence of GERD. Funding Agencies None

Abstract Background Functional esophageal symptoms such as heartburn and dysphagia are common, often occurring in the absence of demonstrable reflux or major motility disorders. Pathophysiology is multifactorial, involving visceral hypersensitivity, altered central processing, and impaired esophageal perception. The relationship between demographic factors and symptom burden in patients with normal motility and no reflux remains unclear. The Esophageal Symptom Questionnaire (ESQ-30) is a validated tool measuring frequency and severity of dysphagia (ESQ-D), reflux (ESQ-R), and globus (ESQ-G). Aims To determine the effect of age and sex on esophageal symptoms in reflux-negative patients with normal esophageal motility. Methods We retrospectively analyzed consecutive high-resolution manometry (HRM) studies between July 2022–October 2024. Inclusion required normal esophageal motility (no esophageal motility disorder by Chicago Classification v4.0) and complete ESQ-30 data. Patients with evidence of GERD by Lyon 2.0 criteria (LA grade B-D esophagitis/Barrett’s esophagus, off-therapy AET &amp;gt;6%, on-therapy AET &amp;gt;4%) were excluded. ESQ subscales were summarized as median (IQR). Group comparisons used Mann-Whitney U tests. Correlations between ESQ subscales, manometric variables (IRP, DCI, % failed, % weak, % incomplete bolus clearance), and age were assessed with Spearman’s bivariate correlations. Results Within the study period, 184 patients (median age 52 [40–62] years, 122 [63.1%] female) met inclusion criteria with normal motility, complete ESQ-30 questionnaires and no evidence of GERD. Median ESQ-D, ESQ-R, and ESQ-G scores were 4 [0–17], 23 [7–41.75], and 16 [4-36], respectively. Females reported higher symptom scores than males: ESQ-D (7.5 vs 1.5, p = .004), ESQ-R (28.0 vs 15.5, p = .012), and ESQ-G (19.5 vs 9, p = .007). Males demonstrated lower mean DCI (p = .024 and 1918.3 vs 2442.2 mmHg●cm●s, p = .029). Increasing age correlated negatively with reflux symptoms (ESQ-R ρ = .178, p = .016) and mean DCI (ρ = .156, p = .035). No other significant associations between age, manometric parameters, or symptoms were observed. Conclusions Symptom profiles in reflux-negative patients with normal esophageal motility vary by age and sex. Women reported greater symptom burden across dysphagia, reflux, and globus domains, while older patients reported fewer reflux symptoms. These findings suggest demographic factors influence symptom perception independent of motility or reflux. Subgroup analyses (e.g., functional heartburn vs functional dysphagia) may clarify pathophysiologic differences and guide individualized management strategies. Funding Agencies None

Substance P (SP) is contained in nerve fibres innervating the oesophageal mucosa and is released into the mucosa during oesophageal acid perfusion. However, the downstream effects of this peripheral SP are not known. We investigated the expression of SP receptors in the oesophageal mucosa of healthy controls and GORD patients, localisation of mast cells in relation to SP+ nerve fibres, and effects of SP exposure on oesophageal epithelial cells. Distal oesophageal biopsies were collected from healthy controls (HC; N=10), functional heartburn (FH; N=10), non-erosive reflux disease (NERD; N=14), and erosive reflux disease (ERD; N=13) patients. IHC was used to determine the cellular expression of the SP receptor, NK1R, on E-Cadherin+, CD3+, and tryptase+ cells. NE-1 oesophageal epithelial cells were incubated with SP to investigate inflammatory pathway activation. The proportion and density of mast cells expressing an SP receptor, MRGPRX2, was analysed, and the distance between SP+ nerve fibres and mast cells was determined. NK1R was expressed on epithelial cells and, rarely, on CD3+ T cells. NK1R fluorescence intensity was significantly higher in NERD and ERD oesophageal mucosa compared with HCs. In NE-1 cells, exposure to SP induced NF-κB phosphorylation, ameliorated by NK1R inhibition, and release of IL-6 and IL-8. In NERD and ERD mucosa, the density of MRGPRX2+ mast cells was significantly higher than HCs. Across all subjects, 25 SP+ nerves were detected; 32% were located within 10 µm of a mast cell, and 84% within 50 µm. Expressions of SP receptors NK1R and MRGPRX2 are upregulated in NERD and ERD oesophageal mucosa, on epithelial cells and mast cells, respectively. Mast cells are also closely apposed to SP+ nerve fibres in the oesophageal mucosa. Furthermore, SP directly induced inflammatory pathway activation and release of cytokines in oesophageal epithelial cells in vitro. Communication between SP+ nerve fibres, epithelial cells, and mast cells may be of pathological significance in GORD.

Abstract Despite its high prevalence in the general population, the diagnosis of Gastroesophageal Reflux Disease (GERD) remains a current challenge. The Montreal and Lyon consensus guidelines provide significant assistance in schematizing this problem; however, their recommendations and protocols cannot be applied in centers where the sophisticated methodology proposed does not exist, such as in Community Hospitals. For nearly six decades, the histological method has been used, with various approaches and success, as a useful procedure in the diagnosis of GERD. Nevertheless, although its description and methodology also date back to that time, the analysis and evaluation of Dilated Intercellular Spaces (DIS) as a histological marker of microscopic esophagitis has been scarcely considered. DIS appear wherever there is damage to the esophageal mucosa, generally caused by refluxed acid and/or alkali, regardless of whether endoscopic lesions are present or not. In this regard, they have been found in very high percentages in erosive GERD but also, with lower frequency, in non-erosive GERD, whether refractory to PPIs or not. The finding of DIS in Hypersensitive Esophagus (physiological pH-metry) is very surprising, and with much lower frequency, similar to that of controls, in Functional Heartburn. This could be explained by the high sensitivity of DIS, which appear even under conditions of minimal or physiological reflux. This review proposes the determination of DIS for the diagnosis of microscopic esophagitis.

Functional Esophageal Disorders in Children.

Background Ambulatory esophageal reflux monitoring allows for objective differentiation of pathologic reflux, reflux hypersensitivity, and functional heartburn. Defining a diagnosis as the etiology of symptoms allows for appropriate medication management, and specifically de-escalation of acid suppression medications such as proton-pump inhibitors. Methods This retrospective chart review examined patients who underwent ambulatory esophageal reflux monitoring within a single health network between September 2021 and January 2024 to determine if appropriate postprocedure medication management occurred. Demographic data, acid suppressive therapy prior to monitoring, results of monitoring, and changes to therapy were reviewed and statistical analysis was performed. Results In the study group, 85 patients were diagnosed with pathologic reflux based on a DeMeester score of ≥14.72; Caucasians and those with a higher body mass index were significantly more likely to be diagnosed with pathologic reflux. Acid suppression was de-escalated in 11 of the 29 patients diagnosed with functional heartburn and 4 of the 33 with reflux hypersensitivity. Conclusion Opportunities remain to improve therapy de-escalation and adjustment in the nonpathologic reflux conditions of reflux hypersensitivity and functional heartburn.

Italian guidelines for the diagnosis and management of gastro-esophageal reflux disease: Joint consensus from the Italian Societies of: Gastroenterology and Endoscopy (SIGE), Neurogastroenterology and Motility (SINGEM), Hospital Gastroenterologists and Endoscopists (AIGO), Digestive Endoscopy (SIED), and General Medicine (SIMG).

Rats with visceral hypersensitivity often exhibit impaired decision-making abilities. Functional heartburn (FH) is a functional esophageal disease that belongs to the category of gut-brain interaction disorders, associated with visceral hypersensitivity. However, the decision-making ability of patients with FH remains unclear. We recruited 30 patients diagnosed with FH based on the Rome IV criteria and 30 healthy controls (HCs). All patients were evaluated using the Hamilton Anxiety Scale and the 17-item Hamilton Depression Scale-17. Patients with FH also completed the gastroesophageal reflux disease and modified gastrointestinal symptom score questionnaires. We employed the Iowa Gambling Task (IGT) and Game of Dice Task (GDT) to evaluate decision making. In the IGT, patients with FH exhibited a lower total net score and made more unfavorable choices compared to healthy controls (HCs). Specifically, statistically significant differences were observed in the net scores of the last three blocks, the differences were of large effect sizes. In the GDT, patients with FH demonstrated a lower total net score, higher risk score, and lower utilization of negative feedback than the HCs, the differences were of middle-large effect sizes. Even after controlling for the effects of anxiety, depression, and the coexistence of functional dyspepsia, patients with FH exhibited lower net scores than HCs, in both the IGT and GDTs. Our findings suggest that patients with FH showed worse decision-making abilities than HCs. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

ABSTRACTBackgroundFunctional dyspepsia (FD) is one of the most common disorders of gut–brain interaction (DGBI). Varying reported population prevalences probably reflect different definitions and methodological approaches.AimTo study the prevalence and impact of FD and its subgroups in an internet survey.MethodsA total of 54,127 respondents from 26 countries completed the survey including the Rome IV diagnostic questionnaire, Patient Health Questionnaire‐4 (PHQ‐4), PHQ‐12, PROMIS Global‐10, demographics, and medical history. Respondents reporting a history of relevant organic disease, or fulfilling criteria for self‐induced or cyclic vomiting, or cannabinoid hyperemesis were excluded.ResultsRome IV FD prevalence was 7.2% (range 2.2%–12.3%), significantly higher in women and decreased with age. The most prominent subtype was postprandial distress syndrome (PDS) (66.6%). Rome IV IBS was found in 26.1% of those fulfilling FD criteria. Functional heartburn and chronic nausea and vomiting criteria were fulfilled in, respectively, 9.0% and 7.0%. Fulfilling FD symptom criteria was significantly associated with increased prevalence of anxiety and depression and with lower quality of life and higher healthcare seeking behaviour.ConclusionsRome IV FD is one of the most prevalent DGBI globally. Across countries, it is associated with female sex, younger age, psychological distress, reduced quality of life, and higher health care utilisation. PDS is the dominant subgroup. Overlapping other DGBI are present in a minority.

ABSTRACTBackgroundMany gastroesophageal reflux disease (GORD) patients have heartburn symptoms despite PPI treatment, potentially via esophageal mucosa exposure to weakly acidic bile salts, leading to oxidative stress. High mobility group box 1 (HMGB1) is a nuclear protein secreted during oxidative stress that binds to receptors including TLR2, TLR4, and RAGE, inducing inflammatory signaling. We describe the release and potential downstream effects of HMGB1 in GORD.MethodsEsophageal biopsies were obtained from healthy controls (HC), functional heartburn (FH), non‐erosive reflux disease (NERD), and erosive reflux disease (ERD) patients. Biopsies were analyzed by RNA‐sequencing, and the expression of TLR2, TLR4, and RAGE was assessed with immunohistochemistry. NE‐1 cells were challenged with pH 5 media and/or 500 μM deoxycholate (DCA), with/without 2‐h 5 or 50 μM curcumin pre‐treatment. HMGB1 translocation was measured with immunofluorescence and release with ELISA.ResultsHMGB1, alongside 12 additional oxidative stress‐associated genes, is over‐expressed in NERD and ERD patients compared to HC (adjusted p < 0.05). Weakly acidic bile salt (pH 5 + DCA) stimulated HMGB1 translocation (p < 0.0001) and release from NE‐1 cells (p < 0.001), but ameliorated with curcumin pre‐treatment. ERD biopsies had increased DAPI+TLR4+ cells (p < 0.05) and TLR4 fluorescence intensity (p < 0.05), compared to HC. RAGE was expressed on CD45+ cells, and the number of RAGE+CD45+ cells was higher in ERD compared to HC (p < 0.05).ConclusionsRelease of HMGB1 from esophageal epithelial cells by weakly acidic bile salts, inhibited by curcumin, and increased expression of TLR4 and RAGE in ERD mucosa suggest this pathway has a role in GORD. Modulating HMGB1 activity may be a strategy for treating recurrent symptoms.

Background/AimsReflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship.MethodsConsecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients.ResultsThe study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis ≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms (55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences.ConclusionsThe study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Gastroesophageal reflux disease (GERD) is a common condition primarily treated with acid-suppressive therapies such as proton pump inhibitors (PPIs) or potassium competitive acid blockers (P-CABs). However, many patients experience a suboptimal response to PPIs or symptom recurrence upon discontinuation, leading to an increased economic burden and reduced quality of life. For patients unresponsive to PPIs, objective tests such as reflux monitoring are essential to differentiate GERD from other conditions or to understand the underlying mechanisms causing the reflux. Strategies like optimizing adherence, dose escalation, switching to other PPIs, or transitioning to P-CABs can improve treatment outcomes. Use of neuromodulators may benefit patients with functional heartburn or reflux hypersensitivity. For those requiring maintenance therapy, explaining the advantages and disadvantages of continuous versus on-demand treatment and providing clear guidance can help achieve effective symptom control with the minimal necessary dosage of the medication. Sequential maintenance therapy, which begins with daily medication and transitions to on-demand therapy, is effective in improving patient satisfaction while minimizing drug exposure.

Mucosal integrity and acid sensitivity predict proton pump inhibitor response in patients with heartburn and normal acid exposure.

The purpose of this study was to evaluate proton pump inhibitor (PPI) response rates for gastroesophageal reflux disease (GERD) phenotypes and functional heartburn (FH) according to the different diagnostic techniques. This was a retrospective, noninterventional, single-center study, presenting real-life data. Among 1,233 patients, 510 patients agreed to respond and were evaluated via a validated questionnaire consisting of 28 questions. Patients were classified into: Group I (n=54) if the diagnosis was based only on history, Group II (n=151) if diagnosis was documented on history and upper gastrointestinal endoscopy (UGE), and Group III (n=305) if diagnosis was based on history, UGE, high-resolution manometry and intraesophageal 24-h ambulatory pH-impedance monitoring. Patients were classified into 5 phenotypes (according to the final diagnosis): erosive esophagitis (EE) (n=117), non-erosive reflux disease (NERD) (n=94), FH (n=58), reflux hypersensitivity (RH) (n=16) and Barrett esophagus (BE) (n=20). A response rate under 50% was accepted as being nonresponsive with double doses after 8 weeks of treatment. A very good response was defined as being over 80% improvement of typical symptoms. The response rates for heartburn and regurgitation of all the patients were 85.3% and 82.2%, respectively. The heartburn and regurgitation response rates of Group I patients were 79.6% and 70.4%; 91.4% and 85.4% for Group II; whereas 83.3% and 82.6% for Group III. The heartburn and regurgitation response rates of BE were 90% and 90%, for EE 88% and 87.2%, for NERD 85.2% and 85.1%, for RH 68.8% and 62.5% and for FH 72.4% and 74.1%. Response rates for both heartburn and regurgination were 40% in BE, 41.4% in EE, 18.8% in NERD, 24.1% in RH and 15.5% in FH. We demonstrated higher PPI response rates than Western populations in all the GERD patients. More than 1/3 of the patients exhibited very good response rates for both heartburn and regurgitation. The response rates of patients who were diagnosed via all the diagnostic modalities are lower than those who were diagnosed via only history and UGE.