Proton Pump Inhibitor Response Research Articles

Practical Application of the COuGH RefluX Score for Patients with Laryngopharyngeal Symptoms: Real-World Assessment in Predicting GERD and PPI Response.

The COuGH RefluX score has been validated to predict likelihood of gastroesophageal reflux disease (GERD) in patients with laryngopharyngeal symptoms (LPS) using parameters of Cough, Overweight, Globus, Hiatal Hernia, Regurgitation, and male seX. This study aimed to assess the real-world value of the COuGH RefluX score in predicting proton pump inhibitor (PPI) response in LPS patients. Patients with LPS for >3 months were prospectively enrolled, and assessed using the Reflux Symptom Index (RSI) and 24-hour impedance-pH monitoring. Based on COuGH RefluX scores, patients were designated unlikely GERD (≤2.5), inconclusive GERD (3.0-4.5), and likely GERD (≥5.0). PPI response was defined as a 50% reduction in RSI. Among 196 participants (mean age 47.8), 121 were unlikely, 60 were inconclusive, and 15 were likely to have GERD. Patients unlikely to have GERD had higher MNBI, lower hiatal hernia prevalence, and fewer confirmed GERD cases compared to inconclusive and likely GERD groups (P <0.05). Symptom severity and AET were similar across groups (P >0.05). PPI response rates were 12.4%, 45.0%, and 73.3% across the groups (P <0.001). Multivariate logistic regression showed COuGH RefluX scores and lower MNBI as independent predictors of PPI responsiveness (scores 3.0-4.5, OR =4.190, P =0.001; scores ≥5.0, OR =15.772, P <0.001; MNBI, OR =0.915, P =0.001). The COuGH RefluX score is effective in predicting GERD and guiding PPI use in LPS patients without esophagitis. The score can ensure appropriate PPI use and targeted testing during initial LPS patient encounters.

Esophageal chest pain resembles heartburn in reflux metrics and response to proton pump inhibitor therapy.

Gastro-esophageal reflux disease (GERD) is the most common cause for noncardiac chest pain (NCCP), with an estimated prevalence rate ranging between 30% and 60%. Heartburn and NCCP may share common mechanisms. To assess whether particular patterns of impedance-pH variables characterize patients with dominant heartburn, regurgitation, or NCCP and their ability to predict proton pump inhibitor (PPI) response for each symptom, GERD patients, evaluated with high-resolution manometry (HRM) and impedance-pH, were included. In total, 109 NCCP, 68 heartburn, and 64 regurgitation patients were included. Pathological reflux episodes were observed in 28%, 19%, and 56% (p < 0.001). Pathological mean nocturnal baseline impedance (MNBI) values were observed in 55%, 53%, and 34% (p < 0.05). Hypomotility was more frequent in NCCP compared to heartburn patients (p < 0.05). When comparing NCCP with heartburn, hypomotility was associated with NCCP perception (OR: 2.34, 95% CI: 1.23-4.43; p < 0.01). When comparing NCCP with regurgitation, >80 refluxes and type 2/3 esophagogastric junction (EGJ) were associated with regurgitation perception (OR: 0.31, 95% CI: 0.16-0.59; p < 0.001, and OR: 0.5, 95% CI: 0.27-0.93; p < 0.05), while pathological MNBI was associated with NCCP perception (OR: 2.34, 95% CI: 1.23-4.43; p < 0.01). 45.5% NCCP patients, 45.6% with heartburn, and 36% with regurgitation responded to PPIs (p < 0.05). At multivariate analysis, pathological MNBI or PSPW index were associated with PPI responsiveness in patients with NCCP or heartburn, while in patients with regurgitation, pathological MNBI was associated with PPI responsiveness and a reflux number >80 to PPI refractoriness. We highlight the usefulness of an accurate clinical and functional evaluation of GERD patients, allowing to discriminate particular characteristics in patients with dominant heartburn, NCCP, or regurgitation, which may benefit of distinct therapeutic strategies.

Clinical Characteristics, Endoscopic Findings, and Treatment Outcomes in Lymphocytic Esophagitis Compared to Eosinophilic Esophagitis.

Lymphocytic and eosinophilic esophagitis (LyE and EoE) are immune-mediated esophageal diseases. Clinical characteristics, endoscopic findings, and treatment outcomes of LyE were compared to EoE. This was an international retrospective study on adults enrolled at three centres in Europe. We recorded clinical characteristics and endoscopy findings at baseline, and symptoms, histology, and endoscopy outcomes following treatment of LyE and EoE patients. Demographics, clinical presentation, comorbidities, and endoscopy findings were largely different in 35 LyE compared to 59 EoE. Proton pump inhibitors (PPIs) response was generally lower in LyE. LyE is clinically different from EoE, but differences in treatment response need further investigation.

Post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance predict proton pump inhibitor response in patients with reflux hypersensitivity.

Post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been shown to influence proton pump inhibitor (PPI) response in GERD patients. However, currently, little data concerning these variables in patients with reflux hypersensitivity (RH) are available. In this study, we aimed to evaluate, in RH patients, the prevalence of PPI responders and nonresponders and investigate the predictive value of impedance-pH variables, including PSPW and MNBI, on responses to PPI. A total of 108 RH patients who met ROME IV criteria were prospectively recruited from June 2018 to December 2022. The prevalence of PPI responders/nonresponders was calculated, and impedance-pH variables were compared between the response and nonresponse groups. Multiple logistic regression was used to investigate predictors for PPI response. Among 108 patients with RH, 60 patients (55.56%) were the PPI responders, and 48 (44.44%) were the nonresponders. Compared with the nonresponders, the PPI responders had a lower PSPW index (47.05±4.43 vs 51.33±3.50, P=0.004) and a decreased value of MNBI (1866.68±390.62 vs 2181.14±338.42, P=0.017). Multivariate logistic regression revealed that only the pathologic PSPW index (OR: 2.064) and MNBI (OR: 1.800) significantly influenced PPI response. Nearly half of RH patients were PPI nonresponders. Impedance-pH monitoring was more valuable than pH-only monitoring in associating PPI response to reflux in RH patients owing to the appraisal of the PSPW index and MNBI.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70–145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient’s age, and patients’ origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.What is Known:• Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness.What is New:• Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy.• PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics.

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies-the only accurate method of assessing PPI response-efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.

Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis.

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.

Baseline Peripheral Eosinophil Count Independently Predicts Proton Pump Inhibitor Response in Eosinophilic Esophagitis.

To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE). PPI leads to histologic remission in ~50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in ~50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear. This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable). One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037). Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission.

Choosing the Therapeutic Strategy in Gastroesophageal Reflux Disease in Pediatric Patients: Is it a Challenge for Clinicians?

Abstract Gastroesophageal reflux disease (GERD) affects 8-33% of individuals worldwide, independent of age or gender. Diagnosis relies on mucosal lesions or symptomatic discomfort, validated by proton pump inhibitor (PPI) response. Lyon Consensus categorizes diagnostic tests as supportive, refuting, or inconclusive. A retrospective cohort study on 78 pediatric subjects at the ‘Sfântul Ioan’ Galați Hospital (February 2018-October 2020) aimed to assess GER incidence and management principles. Data analyzed using SPSS v26 revealed urban predominance (66.7%) and varied age distribution (1 month to 18 years), with heartburn as a prevalent symptom. Treatment modalities included antacids, PPIs, H2RAs, and prokinetics. Symptom relief and therapeutic response guided management, with PPIs commonly administered. This study underscores the need for comprehensive GERD diagnosis and tailored therapeutic strategies in pediatric populations.

A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation, but also heterogeneous presentations involving fibrostenotic esophageal remodeling and esophageal dysmotility. We aimed to define and evaluate phenotypes of EoE using functional lumen imaging probe (FLIP) panometry (ie, a PhysioMechanical classification of EoE). Patients with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP studies were analyzed for distensibility plateau and compliance of the esophageal body, maximum esophagogastric junction diameter, and contractile response pattern. These FLIP features were then applied to define PhysioMechanical classifications. A total of 215 patients with EoE (mean [standard deviation] age 38 [12] years; 31% female) were included. Seven PhysioMechanical classifications were identified that differed by various clinical characteristics, including symptom duration (P < .001) and Endoscopic EoE Reference Scores (EREFS) (P < .001). In particular, patients with "nonreactive fibrostenosis" (n= 14), had greater symptom duration (median [interquartile range] 20 [10-30] years) and more frequently had EREFS grade 2 or 3 ring scores (14 of 14 patients) than patients with a "normal" PhysioMechanical classification (symptom duration: 3 [1-8] years; 4 of 50 [8%] had EREFS grade 2 or 3 rings). In addition, among patients off treatment at cross-sectional evaluation (n= 46), there was a difference between PhysioMechanical classifications in future proton pump inhibitor (PPI) response rates (ie, achieving peak mucosal eosinophil count <15 per high-powered field after PPI treatment); P= .009. PPI response ranged from 87% (13 of 15 patients) with "isolated esophagogastric junction outflow obstruction" to 11% (1 of 9 patients) with "spastic-reactive fibrostenosis." Classifying PhysioMechanical esophageal function in EoE based on FLIP panometry features may facilitate defining disease severity and directing management in EoE.

Relevance of Excessive Air Swallowing in GERD Patients With Concomitant Functional Dyspepsia and Poor Response to PPI Therapy.

The present study was aimed at evaluating the possible role of air swallowing in the association between gastroesophageal reflux disease (GERD) symptoms and concomitant functional dyspepsia (FD) and their role in GERD symptom persistence despite proton pump inhibitor (PPI) therapy. It has been shown that individuals with excessive air swallowing experience FD. It has been also demonstrated that a consistent group of GERD patients not responding to PPI therapy swallow more air during mealtime and also have more mixed refluxes. Multichannel intraluminal impedance-pH tracings from consecutive patients were retrospectively evaluated. A validated structured questionnaire was used to evaluate GERD and concomitant FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard-dose PPI therapy. A total of 35 patients with conclusive GERD, 35 patients with reflux hypersensitivity, and 35 with functional heartburn were studied. A direct relationship was observed between the number of air swallows and of mixed refluxes ( R =0.64). At receiver operating characteristic curve analysis, air swallows and mixed refluxes were significantly associated to the presence of FD and PPI refractoriness. An air swallow cutoff of 107 episodes/24 hours was identified to discriminate patients with and without FD (sensitivity: 87%, specificity: 82.8%). A mixed reflux cutoff of 34 episodes/24 hours was identified to discriminate PPI responders from nonresponders (sensitivity: 84.8%, specificity: 69%). At multivariate analysis, an abnormal number of air swallows and of mixed refluxes were significantly associated to FD and PPI refractoriness. Our study highlights the relevant role of excessive air swallowing in eliciting both dyspepsia and refractoriness of typical GERD symptoms to PPI therapy.

Ambulatory pH-Impedance Findings Confirm That Grade B Esophagitis Provides Objective Diagnosis of Gastroesophageal Reflux Disease.

The Lyon Consensus designates Los Angeles (LA) grade C/D esophagitis or acid exposure time (AET) >6% on impedance-pH monitoring (MII-pH) as conclusive for gastroesophageal reflux disease (GERD). We aimed to evaluate proportions with objective GERD among symptomatic patients with LA grade A, B, and C esophagitis on endoscopy. Demographics, clinical data, endoscopy findings, and objective proton-pump inhibitor response were collected from symptomatic prospectively enrolled patients from 2 referral centers. Off-therapy MII-pH parameters included AET, number of reflux episodes, mean nocturnal baseline impedance, and postreflux swallow-induced peristaltic wave index. Objective GERD evidence was compared between LA grades. Of 155 patients (LA grade A: 74 patients, B: 61 patients, and C: 20 patients), demographics and presentation were similar across LA grades. AET >6% was seen in 1.4%, 52.5%, and 75%, respectively, in LA grades A, B, and C. Using additional MII-pH metrics, an additional 16.2% with LA grade A and 47.5% with LA grade B esophagitis had AET 4%-6% with low mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index; there were no additional gains using the number of reflux episodes or symptom-reflux association metrics. Compared with LA grade C (100% conclusive GERD based on endoscopic findings), 100% of LA grade B esophagitis also had objective GERD but only 17.6% with LA grade A esophagitis ( P < 0.001 compared with each). Proton-pump inhibitor response was comparable between LA grades B and C (74% and 70%, respectively) but low in LA grade A (39%, P < 0.001). Grade B esophagitis indicates an objective diagnosis of GERD.

Assessment of the clinical and allergy profiles of PPI responsive and non-responsive eosinophilic esophagitis.

A subset of patients with eosinophilic esophagitis (EoE) respond to proton-pump inhibitor (PPI) therapy, however they cannot be distinguished prior to PPI trial and the mechanism of PPI response remains unclear. Improved understanding of the distinct patient phenotypes in PPI-responsive EoE (PPI-r-EoE), PPI-non-responsive EoE (PPI-nr-EoE) and erosive esophagitis (EE) may help guide management. The aim of this paper is to compare the clinical and allergy profiles of PPI-r-EoE versus PPI-nr-EoE and EE. This was a retrospective case-control study of EoE patients (>15 eos/hpf on esophageal biopsies) at a tertiary center. EE controls were identified from the pathology database. EoE patients were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response to twice-daily PPI for ≥8weeks. Patient demographics, comorbidities, symptoms, allergy history and endoscopic findings were recorded. Univariate analyses were performed using the Fisher-exact test or t-test. Multivariable analyses were performed using logistic regression. In all, 104 EoE (57 PPI-r-EoE/47 PPI-nr-EoE) and 80 EE subjects were included. On multivariable analyses, allergic conditions (aOR 20.1, P < 0.0001) and rings (aOR 108.3, P = 0.001) were independent predictors for PPI-r-EoE versus EE, whereas allergic conditions (aOR 4.8, P = 0.03), rings (aOR 27.5, P = 0.002) and furrows (aOR 17.1, P = 0.04) were independent predictors for PPI-nr-EoE versus EE. Esophageal rings was the only significant predictor found in PPI-nr-EoE versus PPI-r-EoE (OR 2.5, P = 0.03). Allergic conditions and esophageal rings are significantly more prevalent in PPI-r-EoE and PPI-nr-EoE compared with EE. PPI-r-EoE appears clinically similar to PPI-nr-EoE and significantly different from EE. Further studies are needed to delineate the underlying pathophysiology of PPI-r-EoE versus PPI-nr-EoE.

Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy.

To assess the short- and long-term efficacy of proton pump inhibitor (PPI) therapy for pediatric eosinophilic esophagitis (EoE) in real-world practice with a step-down strategy, and to evaluate factors predictive of PPI responsiveness. We collected data regarding the efficacy of PPIs during this cross-sectional analysis of the prospective nationwide RENESE registry. Children with EoE treated with PPI monotherapy were included. Histological remission was defined as a peak eosinophilic count of <15 eosinophils (eos)/high-power field (hpf). Factors associated with PPI responsiveness were identified using multivariate logistic regression analysis. After induction therapy, histological and clinico-histological remission were observed in 51.4% (n = 346) and 46.5% of children, respectively. Normal endoscopic appearance of the esophagus was associated with a higher possibility [odds ratio (OR), 9.20; 95% confidence interval (CI), 2.10-40.16], and fibrostenotic phenotype was associated with a lower possibility (OR, 0.36; 95% CI, 0.18-0.74) of histological remission. Long-term therapy with a step-down strategy effectively maintained histological remission in 68.5% and 85.3% of children at 7 months (n = 108) and 16 months (n = 34), respectively. Complete initial histological remission (≤5 eos/hpf) was associated with a higher possibility of sustained histological remission (OR, 5.08; 95% CI, 1.75-14.68). Adverse events were infrequent and mild. We confirmed the efficacy of PPIs for a large cohort of children with EoE with sustained histological remission using a step-down strategy. Children with fibrostenotic phenotypes are less likely to respond to induction therapy. Furthermore, patients with complete initial histological remission are more likely to experience long-term histological remission.

Mean Nocturnal Baseline Impedance and Post-reflux Swallow-induced Peristaltic Wave Index Could Identify Gastroesophageal Reflux Disease but pH-Impedance Metrics Alone Might Not Correlate With Proton Pump Inhibitor Response in Chinese Patients With Typical Reflux Symptoms.

Background/AimsLyon consensus differentiates acid exposure time (AET) as physiological, borderline, and pathological. Mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWi) are believed to increase diagnostic yield of gastroesophageal reflux disease (GERD) and correlate with symptom outcome of proton pump inhibitor (PPI) treatment. We aim to explore the clinical characteristics and the correlation of pH-impedance parameters with PPI response in Chinese patients with different AET levels.MethodsWe retrospectively investigated 177 patients with typical reflux symptoms who received esophageal function tests. The demographics, GERD questionnaire scores, the proportion of esophagitis and PPI responders, and manometric and pH-impedance parameters were compared among patients with AET < 4%, 4-6%, and > 6%. In patients with AET ≥ 4%, manometric and pH-impedance parameters were compared between PPI responders and non-responders.ResultsAmong 177 patients, 69 (39.0%) had AET 4-6%, and 53 (29.9%) had AET > 6%. The demographics, esophagogastric junction type, and occurrence of ineffective esophageal motility were similar between patients with AET 4-6% and > 6%, but different from AET < 4%. MNBI and PSPWi were different among different AET levels, but similar between PPI responders and non-responders in patients with AET ≥ 4%.ConclusionsIt is reasonable to set 4% as a threshold to define pathological AET in Chinese patients. MNBI and PSPWi could identify GERD patients, but may not correlate with PPI response of Chinese GERD patients.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Esophageal epithelial immunoglobulin G is an important marker for the diagnosis and management of pediatric eosinophilic esophagitis

Background and AimOur primary aim was to describe the prevalence of immunoglobulin G (IgG) and its subclass IgG4 in immunohistochemistry staining in esophageal biopsy specimens of children with eosinophilic esophagitis (EoE) compared with that of specimens from children with gastroesophageal reflux disease (GERD).MethodsEsophageal biopsy specimens from children with EoE or GERD were stained prospectively for IgG and IgG4 antibodies. Subjects with EoE were divided into cohorts with either active EoE or EoE in remission. Active EoE cases were further divided into proton pump inhibitor responsive (PPI‐r) and PPI‐nonresponsive (PPI‐nr) subgroups. Demographic, clinical, and histologic data were compared among groups, including quantified IgG and IgG4 staining, peak eosinophil count, eosinophil‐derived neurotoxin levels, and EoE endoscopic reference score.ResultsSeventy‐nine children (aged 10.6 ± 5.6 years; 68% male) were enrolled. IgG‐positive cell counts were significantly elevated in those with active EoE (n = 29, 3 [interquartile range, IQR: 2–6]/high‐powered field [HPF]), compared with those having EoE remission (n = 25, 1 [IQR: 0–2]/HPF; P = 0.002) and those with GERD (n = 25, 0 [IQR: 0–0.25]/HPF, P = <0.0001). IgG‐positive cell counts were significantly higher in the PPI‐r (n = 15, 5 [IQR: 2.5–11]/HPF) subgroup, compared with the PPI‐nr subgroup (n = 11, 3 [IQR: 1.5–3.5]/HPF; P = 0.041) at baseline endoscopy.ConclusionInitial esophageal tissue biopsy specimens from pediatric subjects with active EoE showed a significant increase in IgG‐positive staining compared with tissue from subjects in EoE remission or with GERD. There was higher positivity of IgG‐stained cells in the PPI‐r subgroup compared with the PPI‐nr subgroup.

Are We Making Progress in the Hunt for Biomarkers that Could Differentiate Proton Pump Inhibitor-Responsive Eosinophilic Esophagitis?

Are We Making Progress in the Hunt for Biomarkers that Could Differentiate Proton Pump Inhibitor-Responsive Eosinophilic Esophagitis?