The role of high-resolution impedance manometry to identify rumination syndrome in children with unexplained foregut symptoms.

OBJECTIVES: Diagnosis of rumination syndrome (RS) relies on Rome IV criteria. Oesophageal high-resolution impedance manometry (HRIM) can objectively demonstrate the episodes of rumination, but its role in the diagnostic pathway is not yet established. We aimed to demonstrate the clinical contribution of this tool for the timely diagnosis of RS and diagnostic work-up of children with unexplained foregut symptoms deemed to be due to other conditions. METHODS: HRIMs performed between 2012 and 2021 were searched to retrieve all diagnoses of RS. Medical records were reviewed for clinical data. RESULTS: Out of 461 HRIMs performed, 76 children had manometric diagnosis of RS (35 male, median age: 13 years). Of them, 47% were not clinically suspected as the symptoms did not fulfil clinical criteria for RS. The indications for HRIM in these cases were investigation of unexplained foregut symptoms (37%), suspected refractory gastroesophageal reflux disease (8%) and dysphagia (2%). Among all HRIMs performed for investigations of unexplained foregut symptoms (n = 80), 35% demonstrated rumination episodes. CONCLUSION: Identification of characteristic patterns of rumination on HRIM in children with unexplained foregut symptoms enables the immediate diagnosis of RS. Thus, in situations of diagnostic uncertainty, the use of HRIM at early stages of the diagnostic pathway would reduce unnecessary investigations and treatments.

Pathophysiology of Pediatric Gastroesophageal Reflux Disease: Similarities and Differences With Adults.

Gastroesophageal reflux (GOR) is defined as "the passage of gastric contents into the esophagus with or without regurgitation and vomiting" and gastroesophageal reflux disease (GORD) is defined "when GOR leads to troublesome symptoms affecting the daily functioning and/or complications." This definition was first developed in 2006 by the Montreal consensus group (1) and later on adopted by pediatric gastroenterology societies such as ESPGHAN and NASPGHAN in 2009 (2). The definition of gastroesophageal reflux reveals little about its pathophysiology and is focused on symptomatology. In this way, it acts as an umbrella term for the multifactorial causes of the disease and the various phenotypes encountered; from functional heartburn to hypersensitive esophagus and nonerosive reflux disease, to erosive esophagitis and Barrett's esophagus. This article is devoted to the pathophysiology of pediatric GORD in comparison to adult GORD and is divided in 2 parts. In the first part, we will systematically describe the different mechanisms for the generation and clearance of reflux events, while on the second part we will discuss the mechanisms involved in symptoms generation. Finally, we will discuss the similarities and differences between pediatric and adult GORD.

Identification of Different Phenotypes of Esophageal Reflux Hypersensitivity and Implications for Treatment.

BACKGROUND & AIMS: Reflux hypersensitivity (RH), a functional esophageal disorder, is detected in 14%-20% of patients who present with typical esophageal symptoms. As many as 40% of patients with RH do not respond to treatment with pain modulators or proton pump inhibitors (PPIs); behavior disorders might contribute to lack of treatment efficacy. We aimed to assess the prevalence of behavioral disorders and their effects on typical reflux symptoms in patients with RH. METHODS: We performed a retrospective study of 542 patients with PPI-refractory esophageal symptoms (heartburn, regurgitation, or chest pain) or with symptoms that responded to PPI therapy, evaluated for anti-reflux surgery from January 2016 through August 2019 at a single center in London, United Kingdom. We collected data on symptoms, motility, and impedance-pH monitoring and assigned patients to categories of RH (n = 116), functional heartburn (n = 126), or non-erosive reflux disease (n = 300). RESULTS: Of the 116 patients with a diagnosis of RH, 59 had only hypersensitivity, whereas 57 patients (49.2%) had either excessive supragastric belching (SGB, 39.7%), based on 24-hour impedance-pH monitoring, or rumination (9.5%), based on postprandial manometry combined with impedance. The prevalence of SGB and rumination in patients with RH was significantly higher than in patients with functional heartburn (22%; P < .001). Patients with RH and rumination were significantly younger (P = .005) and had the largest number of non-acid reflux episodes (P = .023). In patients with RH with SGB, SGB episodes were associated with 40.6% of marked reflux symptoms (heartburn, regurgitation, or chest pain), based on impedance-pH monitoring. In patients with RH and rumination, 40% of reflux-related symptoms (mostly regurgitation) were due to possible rumination episodes. CONCLUSIONS: Almost half of patients with a diagnosis of RH have behavior disorders, including excessive SGB or rumination. Episodes of SGB or rumination are associated with typical reflux symptoms. Segregation of patients with diagnosis of RH into those with vs without behavioral disorders might have important therapeutic implications.

Esophageal Mucosa Innervation in Children With Nonerosive Reflux Disease.

INTRODUCTION: Esophageal mucosa innervation in adults with nonerosive reflux disease (NERD) is more superficial compared with healthy volunteers. We delineated the esophageal mucosal innervation in pediatric NERD and controls. METHODS: Distal and proximal pediatric esophageal biopsies were immunohistochemically stained with calcitonin gene-related peptide and transient receptor potential cation channel subfamily V member 1. RESULTS: Mucosal innervation was assessed in 18 controls (9M:9F, median age: 9 years) and 11 NERD patients (6M:5F, median age: 5 years). Calcitonin gene-related peptide positive nerve fibers were lying deep in the mucosa in both groups, P > 0.05 and did not coexpress transient receptor potential cation channel subfamily V member 1. DISCUSSION: The pediatric esophageal mucosa in NERD displays deep lying nerve fibers, in contrast to adults.

Rumination Syndrome in Children Presenting With Refractory Gastroesophageal Reflux Symptoms.

OBJECTIVES: Up to 40% of children presenting with reflux symptoms do not respond to standard medical interventions. In adults, 20% of patients presenting with Proton Pump Inhibitors refractory Gastro-Esophageal Reflux Disease (GERD) have rumination syndrome. The management of GERD and rumination differ significantly. Our study aimed to identify rumination syndrome amongst children presenting with persistent GERD symptoms based on a distinct pattern on impedance-pH monitoring. METHODS: The parameters of impedance-pH monitoring were compared between children with rumination syndrome (n = 12), diagnosed on high-resolution manometry impedance (HRM/Z), children with GERD (n = 18), children with an alternative diagnosis (non-GERD, n = 12) and children negative for rumination based on HRM/Z (n = 14). The parameters that distinguish the rumination group were identified and incorporated into a scoring system, which was blindly applied on a separate group of children with refractory GERD (n = 18) to define its sensitivity and specificity. RESULTS: Rumination syndrome presents in 44% of children with refractory GERD. Children with rumination syndrome present with a large number of proximal reflux episodes (>57.5 episodes/24 hours); a high frequency of nonacid reflux events in the postprandial period (>2/hour); and a highly positive symptom-reflux association analysis (SAP ≥ 95%). A score of ≥2 out of the 3 points distinguishes children with rumination syndrome with 75% sensitivity and 80% specificity. CONCLUSIONS: Children with rumination syndrome have a distinct pattern of impedance-pH monitoring and can be distinguished amongst children presenting with refractory GERD. Applying a simple scoring system during impedance-pH analysis could lead to early diagnosis of children with rumination syndrome.

Measurement of Salivary Pepsin to Detect Gastroesophageal Reflux Disease Is Not Ready for Clinical Application.

A noninvasive test for gastroesophageal reflux disease (GERD) is desirable for adults and children. Salivary pepsin measurement has been proposed as such a test.1-3 A previous study from our group demonstrated that a maximal salivary pepsin cutoff of >210 ng/mL using the PepTest device (RD Biomed, Hull, United Kingdom) had excellent specificity of 96% but modest sensitivity of 44% to diagnose GERD,4 leading to optimism about its potential use. In this study, we aimed to confirm the previously reported sensitivity and specificity in healthy volunteers and patients with heartburn, evaluate the association between a positive PepTest and response to proton pump inhibitor (PPI) therapy, assess if test-sensitivity can be improved for GERD when samples are taken over a 72-hour sampling period, and establish normal values of salivary pepsin in infants.

Persistent Postprandial Regurgitation vs Rumination in Patients With Refractory Gastroesophageal Reflux Disease Symptoms: Identification of a Distinct Rumination Pattern Using Ambulatory Impedance-pH Monitoring.

OBJECTIVES: Up to 20% of patients with refractory gastroesophageal reflux disease (GERD) might have postprandial rumination. The aim of this study was to distinguish persistent GERD-related postprandial regurgitation from rumination in patients with refractory GERD undergoing ambulatory multichannel intraluminal impedance-pH (MII-pH) monitoring. METHODS: We first characterized 24-hour and postprandial MII-pH patterns in 28 consecutive patients with confirmed rumination syndrome (positive clinical and high-resolution manometry/impedance). We compared such MII-pH patterns with those from 30 patients with typical GERD symptoms (10 nonerosive reflux disease, 10 hyperactive esophagus, and 10 functional heartburn) and 27 healthy controls. Using ROC curves, we selected the best MII-pH parameters to prepare an MII-pH rumination score. We prospectively tested the performance of the new MII-pH rumination score in 26 consecutive patients with refractory GERD (predominant regurgitation). RESULTS: Compared with GERD controls, patients with rumination were more often females, younger, and had significantly more postprandial early nonacid reflux episodes with high proximal extent. Postprandial reflux in ruminators had a distinct nadir pH profile over time (from nonacid to acid). Despite increased reflux events, baseline impedance in ruminators was similar to that in healthy subjects. Ruminators marked postprandial symptoms earlier and much more often than patients with GERD. An MII-pH-based rumination score (using postprandial nonacid reflux/hour and Symptom Index) diagnosed rumination in 46% of patients with refractory GERD and persistent regurgitation (sensitivity 91.7% and specificity 78.6%). DISCUSSION: Postprandial rumination is very common in refractory GERD with persistent regurgitation. A simple MII-pH score detects rumination in these patients with high sensitivity and specificity.

Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease.

BACKGROUND & AIMS: Little is known about the causes of heartburn in patients with gastro-esophageal reflux disease. Visible epithelial damage is seldom associated with symptom severity, evidenced by the significant symptom burden in patients with nonerosive reflux disease (NERD) compared with patients with erosive reflux disease (ERD) or Barrett's esophagus (BE). We studied the distribution of mucosal nerve fibers in patients with NERD, ERD, and BE, and compared the results with those of healthy subjects. METHODS: We performed a prospective study of 13 patients with NERD, 11 patients with ERD, and 16 patients with BE undergoing endoscopic evaluation in the United Kingdom or Greece. Biopsies were obtained from the proximal and distal esophageal mucosa of patients with NERD, from the distal esophageal mucosa of patients with ERD, and the distal-most squamous epithelium of patients with BE. These were examined for the presence and location of nerve fibers that reacted with a labeled antibody against calcitonin gene-related peptide (CGRP), a marker of nociceptive sensory nerves. The results were compared with those from 10 healthy volunteers (controls). RESULTS: The distribution of CGRP-positive nerves did not differ significantly between the distal esophageal mucosa of controls (median, 25.5 cell layers to surface; interquartile range [IQR], 21.4-28.8) vs patients with ERD (median, 23 cell layers to surface; IQR, 16-27.5), or patients with BE (median, 21.5 cell layers to surface; IQR, 16.1-27.5). However, CGRP-positive nerves were significantly more superficial in mucosa from patients with NERD-both distal (median, 9.5 cell layers to surface; IQR, 1.5-13.3; P < .0001 vs ERD, BE, and controls) and proximal (median, 5.0 cell layers to surface; IQR, 2.5-9.3 vs median 10.4 cell layers to surface; IQR, 8.0-16.9; P = .0098 vs controls). CONCLUSIONS: Proximal and distal esophageal mucosa of patients with NERD have more superficial afferent nerves compared with controls or patients with ERD or BE. Acid hypersensitivity in patients with NERD might be partially explained by the increased proximity of their afferent nerves to the esophageal lumen, and therefore greater exposure to noxious substances in refluxate.

Chicago Classification of Esophageal Motility Disorders: Applications and Limits in Adults and Pediatric Patients with Esophageal Symptoms.

The Chicago classification (CC) is most valued for its systematic approach to esophageal disorders and great impact in unifying practice for esophageal manometric studies. In view of the ever-growing wealth of knowledge and experience gained by the expanding use of high-resolution manometry (HRM) in various clinical scenarios, the CC is regularly updated. Its clinical impact and ability to predict clinical outcome, both in adults and pediatrics, will be further promoted by recognizing its current limitations, incorporating new metrics in its diagnostic algorithms and adjusting the HRM protocols based on the clinical question posed. Herein, we discuss the current limitations of the CC and highlight some areas of improvement for the future.

Chronic recurrent multifocal osteomyelitis and inflammatory bowel disease.

Chronic recurrent multifocal osteomyelitis (CRMO) has been reported in association with inflammatory bowel disease (IBD), mostly in children. We describe the UK paediatric experience of CRMO and IBD and review the global literature. Three cases of CRMO and IBD were identified in UK children during the last 10 years. This adds to the previously published 24 cases worldwide (15 children). We provide further evidence for the true association of CRMO and IBD, and a greater understanding of disease course. CRMO may be considered a rare extraintestinal complication of IBD.

Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders.

BACKGROUND: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role. AIMS: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders. METHODS: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High-resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene-related peptide (CGRP)-immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers. RESULTS: Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP-immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP-immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = -0.567, p < 0.001) and distal oesophagus (ρ = -0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008). CONCLUSIONS: Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow.

Recent advances in the treatment of gastrointestinal motility disorders in children.

INTRODUCTION: Pediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact. AREAS COVERED: PubMed and Medline databases were searched for relevant articles related to the treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017 and 2022. In this article, we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments. EXPERT OPINION: Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement, such as ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation.

Optimizing nutrition IN pediatric intestinal pseudo-obstruction syndrome.

BACKGROUND: Pediatric intestinal pseudo-obstruction (PIPO) encompasses a variety of rare, heterogeneous, and disabling disorders that severely affect gastrointestinal motility and are associated with high morbidity and mortality. PIPO management is complex and focuses on maintaining an optimal nutritional status, improving gut function, relieving symptoms, and treating complications. Nutritional issues prevail, and PIPO patients often experience severe undernutrition and faltering growth. Thus, nutritional management plays a pivotal role for achieving the most favorable clinical outcomes. The calorie and nutrient intake of each patient needs to be tailored to age, extent and severity of gut involvement and nutritional needs to support an optimal nutritional status. After defining the extent and severity of gut dysmotility, an experienced team should perform a careful nutritional assessment. An oral diet should always be encouraged and might include bite and dissolve solids, liquid diet or simple oral stimulation. If oral caloric intake is inadequate, liquid gastric feeds should provide the subsequent step. In the presence of severe gastric dysmotility, continuous post-pyloric feeding represents a viable option. In the most severe cases, parenteral nutrition (PN) is required to meet appropriate nutritional requirements. PURPOSE: Pediatric data on this topic are scarce and mainly extrapolated from adult studies. In this review, we discuss current evidence and knowledge regarding nutritional options, implications of the use of different feed types, including a blended diet, and the use of PN. Moreover, based on our experience and the evidence from the literature, we propose a flow chart to guide the nutritional management of PIPO patients.

Belching in children: Prevalence and association with gastroesophageal reflux disease.

BACKGROUND: Excessive belching is frequently reported in adult patients with gastro-oesophageal reflux disease (GORD) and dyspepsia. Although postprandial gastric belching (GB) is considered a physiological mechanism for gastric venting, supra-gastric belching (SGB) is considered a distinct behavioural disorder. We aimed to define the prevalence of different types of belching and its association with reflux disease in paediatric patients. METHODS: We retrospectively analysed reflux monitoring studies from 287 patients (median age: 7.0 years; interquartile range 3.0-11.3 years) with a suspicion of GORD. Based on oesophageal acid exposure time (AET) patients were divided in 3 groups: (a) physiological AET, (b) borderline AET and (c) pathological AET. MII-pH studies were manually edited and reflux disease parameters were measured together with quantification of GB and SGB. KEY RESULTS: Two hundred one children (70.0%) had physiological AET (median: 0.8; interquartile range 0.3-1.6), 52 (18.1%) had borderline AET (median: 4.2; interquartile range 3.4-5.3) and 34 (11.9%) had pathologic AET (median: 10.7; interquartile range 9.1-14.2). Gastric belching was observed in all studies. Gastric belching related reflux was more frequently observed in patients with borderline and pathological AET (p < 0.001). This was more common in older children. SGB were observed in only 7 (2.4%) children (age range: 8-17years) in our population and all patients had Physiological AET. Only 3 (1%) patients had pathological number of SGB (>13/24 h). CONCLUSIONS AND INFERENCES: Gastric belching related reflux is observed in children with increased AET. SGB is very rare in the paediatric population.

Gastroesophageal Reflux Disease and Foregut Dysmotility in Children with Intestinal Failure.

Gastrointestinal dysmotility is a common problem in a subgroup of children with intestinal failure (IF), including short bowel syndrome (SBS) and pediatric intestinal pseudo-obstruction (PIPO). It contributes significantly to the increased morbidity and decreased quality of life in this patient population. Impaired gastrointestinal (GI) motility in IF arises from either loss of GI function due to the primary disorder (e.g., neuropathic or myopathic disorder in the PIPO syndrome) and/or a critical reduction in gut mass. Abnormalities of the anatomy, enteric hormone secretion and neural supply in IF can result in rapid transit, ineffective antegrade peristalsis, delayed gastric emptying or gastroesophageal reflux. Understanding the underlying pathophysiologic mechanism(s) of the enteric dysmotility in IF helps us to plan an appropriate diagnostic workup and apply individually tailored nutritional and pharmacological management, which might ultimately lead to an overall improvement in the quality of life and increase in enteral tolerance. In this review, we have focused on the pathogenesis of GI dysmotility in children with IF, as well as the management and treatment options.

Measurement of Esophageal Nocturnal Baseline Impedance: A Simplified Method.

BACKGROUND/AIMS: Mean nocturnal baseline impedance (MNBI) during multichannel intraluminal impedance pH-monitoring (MII-pH) reflects the status of esophageal mucosal integrity. MNBI is suggested as an adjunctive method to distinguish patients with true gastroesophageal reflux disease (GERD) from functional heartburn (FH) and might predict outcomes for anti-reflux treatment. However, current methodology for calculation of MNBI is time-consuming and subject to operator-dependent selection bias. We aim to simplify and provide a more objective method to calculate MNBI. METHODS: We retrospectively analyzed 100 MII-pH tracings from 20 patients with erosive reflux disease, 20 with non-erosive reflux disease (NERD), 20 with reflux hypersensitivity, 20 with functional heartburn (FH), and 20 healthy asymptomatic volunteers. We compared the current "conventional" MNBI analysis with our "simple" MNBI analysis measured by selecting the whole supine period using the impedance average calculation function in the MII-pH software. RESULTS: Absolute values were very similar and there was a strong correlation between conventional and simple MNBI values in the most distal channel in all groups (r ≥ 0.8, P < 0.001) including patients with increased supine acid reflux. Distal esophageal simple MNBI negatively correlated with acid exposure time (r = -0.695, P < 0.001). Patients with erosive reflux disease and NERD had lower simple MNBI values in the most distal channel compared to other groups (P < 0.001). With a cutoff value of 1785 ohms, simple MNBI can discriminate patients with GERD from those with reflux hypersensitivity and FH (sensitivity 80.0% and specificity 89.7%). CONCLUSION: Simple MNBI analysis provides very similar values and has an excellent correlation with conventional MNBI analysis.

Exacerbation of gastroesophageal reflux symptoms after discontinuation of proton pump inhibitors is not associated with increased esophageal acid exposure.

BACKGROUND: Discontinuation of long-term proton pump inhibitors (PPIs) on patients with reflux symptoms can be challenging, as symptoms often exacerbate after stopping. The mechanism remains unknown. Our aim was to evaluate the impact of stopping long-term PPIs on patients with heartburn, and its association with esophageal acid exposure. METHODS: Patients with heartburn on long-term PPIs underwent symptom questionnaire, high-resolution manometry, and 24h ambulatory impedance-pH studies, following a 7-day PPIs discontinuation. We investigated the association between exacerbation of symptoms and findings on ambulatory reflux studies. KEY RESULTS: We studied 37 patients. After stopping PPIs, 27 patients (73%) had exacerbation of heartburn. Esophageal acid exposure time% (AET) in patients with exacerbation of heartburn was not significantly higher than in patients without (3.5% [1.3-9.7] vs 2.5% [1.3-8.7], NS). Fourteen of 27 patients with exacerbation had physiological AET (<4%) as compared with 6 of 10 patients with physiological AET (NS). All questioned symptoms (heartburn, regurgitation, epigastric discomfort/pain, bloating/belch) worsened after stopping PPIs (NS). CONCLUSIONS & INFERENCES: Exacerbation of heartburn after discontinuation of PPIs does not appear to be due to increased esophageal acid exposure.

Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non-erosive reflux disease patients.

BACKGROUND: Mucosal innervation in non-erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux-symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV. METHODS: Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP-positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD. RESULTS: Eleven patients were included in the FH group with a mean age of 46 years (range 33-69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4-28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5). CONCLUSIONS: The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology.

Adult and paediatric GERD: diagnosis, phenotypes and avoidance of excess treatments.

Detailed investigations and objective measurements in patients with symptoms of gastro-oesophageal reflux should be performed with the intent of making the correct diagnosis, thus enabling choice of appropriate therapy. Establishing the most effective therapy is particularly important in adults who do not respond to standard treatment and in children. The use of PPIs for suspected GERD has increased substantially over the past decade, providing great relief in patients with acid-related symptoms, but also leading to adverse effects and a considerable economic burden. Adults with functional heartburn do not benefit from PPIs, while prolonged PPI use in patients with extraoesophageal symptoms remains a controversial area. Moreover, PPIs are not indicated in infants with GERD unless symptoms are proven to be acid-related. With regard to antireflux surgery, patients must be carefully selected to avoid the need for ongoing PPI treatment postoperatively. Correct diagnosis and phenotyping of patients with symptoms attributed to gastro-oesophageal reflux through detailed investigations is therefore imperative, leading to improved patient outcomes and rationalized use of available treatment options. In this Review, we outline currently available diagnostic tests and discuss approaches to limit any unnecessary medical or surgical interventions.