Gastroesophageal reflux disease (GERD) is a common comorbidity associated with congenital diaphragmatic hernia (CDH), with reported cases of Barrett's esophagus (BE) and esophageal adenocarcinoma before the age of 25. The prevalence and natural course of GERD in CDH survivors remain uncertain due to variations in diagnostic methods. We aimed to analyse the GERD prevalence from infancy through young adulthood.

We retrospectively analyzed pH-impedance measurements and endoscopic findings in 96 CDH survivors evaluated as routine care using well established clinical protocols. GERD was defined as an abnormal acid exposure time for pH-MII measurements and as presence of reflux esophagitis or BE at upper endoscopy. Clinical data including symptoms at time of follow-up and use of antireflux medication were collected.

GERD prevalence remained consistently low (≤10%) across all age groups, yet many patients experienced GER symptoms. Histological abnormalities were observed in 80% of adolescents and young adults, including microscopic esophagitis in 50%. BE was diagnosed in 7% before the age of 18, all had GER symptoms. CDH severity, anatomy at the time of CDH correction, alcohol usage, and smoking did not emerge as significant risk factors for GERD.

Given the low GERD prevalence in CDH survivors, a symptom-driven approach to diagnosis and follow-up is warranted. We advise long-term follow-up for all adult patients due to the early onset of BE and the limited evidence available. The longitudinal course and impact of GERD on other long-term CDH-related comorbidities should be explored in larger cohorts.

Not applicable.

Chronic cough in children is closely related to gastroesophageal reflux (GER). However, this association has not been adequately studied due to a lack of diagnostic tools. Combined esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring is considered the most accurate method for evaluating the association between symptoms and reflux, but data on its use in children with chronic cough are still lacking. We aimed to assess the association between chronic cough and GER in children through MII-pH monitoring.

Children with chronic cough (> 4 weeks) who were suspected gastroesophageal reflux disease(GERD) were selected to undergo 24 h MII-pH monitoring at our hospital. Patients were divided into groups according to their age, body position, reflux index (RI) or total reflux events, and the differences between the groups were analyzed. Then the significance and value of 24 h pH and impedance monitoring in chronic cough and the relationship between chronic cough and reflux were discussed.

Overall, 426 patients were included. The median age was 12 months (interquartile range: 6-39.5 months), 129 (30.3%) patients had RI > 7% detected by pH-metry, and 290 (68.1%) patients had positive diagnosis based on the impedance data. GER predominantly occurred in the upright position and mostly involved weakly acidic reflux and mixed gas-liquid reflux. There were 14.1% of children in non-acid GER group were SAP positive showing no difference in acid GER group 13.2% (P = 0.88), whereas patients with SAP > 95% in MII positive group (47[16.2%]) is higher than in MII negative group (P < 0.05).

Twenty four hour MII-pH monitoring is safe, well tolerated in children, but also has a higher detection rate of gastroesophageal reflux. It can find identify weakly acidic reflux, weakly alkaline reflux and reflux events with different physical properties, which can explain the relationship between GER and chronic cough more comprehensively. It provides new approach for exploring the etiology, diagnosis and treatment of children with chronic cough.

Pediatric age esophageal diseases are rare and complex clinical conditions. Treatment options should be individually determined for the patient. The advances in the follow-up and treatment process is the most important reason for the increase in survival time, particularly for congenital pediatric surgical diseases. This study aimed to evaluate the general characteristics of pediatric surgical esophageal diseases in light of the literature.

Gastroesophageal reflux (GER) in children is very common and refers to the involuntary passage of gastric contents into the esophagus. This is often physiological and managed conservatively. In contrast, GER disease (GERD) is a less common pathologic process causing troublesome symptoms, which may need medical management. Apart from abnormal transient relaxations of the lower esophageal sphincter, other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense, impaired esophageal and gastric motility and clearance, as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia. The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation. Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD. The following review focuses on up-to-date information regarding of the pathogenesis, diagnostic evaluation and management of GERD in children.

Bile reflux may cause for lung allograft rejection, yet there are no studies that determine (i) the relationship between gastric and lung bile concentrations, (ii) whether bile is present in lungs of nontransplant patients, (iii) the relationship between gastric dysmotility and lung bile, (iv) the impact of reflux therapies on lung bile, and (v) whether lung bile worsens outcomes in nontransplant patients. This study will address these gaps in the literature.

We prospectively recruited lung transplant (LTX) patients and nontransplant patients with respiratory symptoms (RP) and collected paired gastric and lung samples. Bile concentration and composition of samples was assessed using liquid chromatography-mass spectrometry. Bile results were compared with clinical parameters, including the presence of esophagitis, gastric dysmotility, and/or pathologic gastroesophageal reflux.

Seventy patients (48 RP and 22 LTX) were recruited. Overall, 100% of gastric and 98% of bronchoalveolar lavage samples contained bile. The mean gastric bile concentrations in RP and LTX patients were 280 ± 703 nmol/L and 1,004 ± 1721 nmol/L, respectively (P = 0.02). There was no difference in lung bile concentrations between RP (9 ± 30 nmol/L) and LTX (11 ± 15 nmol/L, P = 0.7). Patients with delayed gastric emptying had higher lung bile concentrations (15.5 ± 18.8 nmol/L) than patients with normal gastric emptying (4.8 ± 5.7 nmol/L, P = 0.05) independently of reflux burden. Proton pump inhibitor use increased the proportion of unconjugated gastric bile acids. High lung bile concentrations were associated with an increased risk of hospitalization and longer hospital stays in RP patients (P < 0.05).

Lung bile is almost universally present in symptomatic patients, and higher concentrations are associated with poorer respiratory outcomes.

The pathophysiological mechanism(s) of gastroesophageal reflux disease (GERD)-related chronic cough (CC) is unclear. We aimed to determine the mechanism of reflux-induced cough by synchronous monitoring of reflux episodes, esophageal motility, and cough.

Patients with GERD were prospectively enrolled and classified into GERD with CC (GERD-CC) and without CC (GERD) groups. Twenty-four-hour ambulatory pH-impedance-pressure monitoring was performed; the reflux patterns, esophageal motility during prolonged exposure to acid and characteristics of reflux episodes that induced coughing paroxysms were analyzed.

Thirty-one patients with GERD-CC and 47 with GERD were enrolled; all of whose monitoring results fulfilled the criteria for diagnosis of GERD. Patients with GERD-CC had higher reflux symptom scores, longer exposure to acid, higher DeMeester scores, and more frequent reflux episodes, proximal extent reflux detected by impedance, and higher percentage of strongly acidic reflux than patients in the GERD group (all P < .05). Of 63 reflux-cough episodes identified in the GERD-CC group, 74.6% of distal reflux and 67.0% of proximal reflux episodes were acidic. More patients had low pan-esophageal pressure in primary peristalsis (48.5% vs 11.8%, P = .000) and synchronous contraction in secondary peristalsis during prolonged exposure to acid in the GERD-CC than in the GERD group (63.9% vs 9.1%, P = .000).

Proximal acidic reflux and distal reflux-reflex are jointly associated with reflux-induced cough in patients with GERD. Low pan-esophageal pressure in primary peristalsis and synchronous contraction in secondary peristalsis may play important roles in GERD-associated chronic cough.

Multichannel intraluminal impedance pH (MII-pH) monitoring currently represents the gold standard diagnostic technique for the detection of gastro-esophageal reflux (GER), since it allows to quantify and characterize all reflux events and their possible relation with symptoms. Over the last ten years, thanks to its strengths and along with the publication of several clinical studies, its worldwide use has gradually increased, particularly in infants and children. Nevertheless, factors such as the limited pediatric reference values and limited therapeutic options still weaken its current clinical impact. Through an up-to-date review of the available scientific evidence, our aim was to produce a position paper on behalf of the working group on neurogastroenterology and acid-related disorders of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) on MII-pH monitoring technique, indications and interpretation in pediatric age, in order to standardise its use and to help clinicians in the diagnostic approach to children with GER symptoms.

The aim of the study was to evaluate acid and nonacid gastroesophageal reflux in infants and school-aged children with esophageal atresia (EA) using pH-impedance (pH-MII) monitoring.

Between 2012 and 2017, all 24-hour pH-MII studies performed in infants (≤18 months) and 8-year olds with EA were included. Antiacid therapy was discontinued before study. Exclusion criteria were: isolated tracheoesophageal fistula; esophageal replacement therapy; tube feeding; and monitoring <18 hours. Automatically detected retrograde bolus movements (RBM) were manually reviewed and modified/deleted if necessary.

We included 57 children (51% boys; 2% isolated EA; 44% thoracoscopic EA repair): 24 infants (median age 0.6 years) and 33 school-aged children (median age 8.2 years). Of the automatically detected 3313 RBM, 1292 were manually deleted from the tracings: 52% of nonacid RBM and 8% of acid RBM (mainly misinterpreted swallows or 1 event recognized as several events). In infants, median reflux index (RI; pH <4) was 2.6% (abnormal in n = 2), median RBM was 61 (62% nonacid, 58% mixed), and median of the mean BCT was 11 seconds. In older children, median RI was 0.3% (abnormal in n = 4), median RBM was 21 (64% nonacid; 75% mixed), and median of the mean BCT was 13 seconds.

Most children with EA off medication have a normal RI, yet experience a significant number of nonacid RBM. After manual revision of the tracings, a high percentage of RBM was deleted. Our data show that automated impedance analysis software needs refinement for use in infants and children with EA and question the need for standard antiacid therapy in these patients.

Whether gastroesophageal reflux (GER) or GER disease (GERD) causes chronic cough in children is controversial. Using the Population, Intervention, Comparison, Outcome (PICO) format, we undertook four systematic reviews. For children with chronic cough (> 4-weeks duration) and without underlying lung disease: (1) who do not have gastrointestinal GER symptoms, should empirical treatment for GERD be used? (2) with gastrointestinal GER symptoms, does treatment for GERD resolve the cough? (3) with or without gastrointestinal GER symptoms, what GER-based therapies should be used and for how long? (4) if GERD is suspected as the cause, what investigations and diagnostic criteria best determine GERD as the cause of the cough?

We used the CHEST Expert Cough Panel's protocol and American College of Chest Physicians (CHEST) methodological guidelines and GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Delphi methodology was used to obtain consensus.

Few randomized controlled trials addressed the first two questions and none addressed the other two. The single meta-analysis (two randomized controlled trials) showed no significant difference between the groups (any intervention for GERD vs placebo for cough resolution; OR, 1.14; 95% CI, 0.45-2.93; P = .78). Proton pump inhibitors (vs placebo) caused increased serious adverse events. Qualitative data from existing CHEST cough systematic reviews were consistent with two international GERD guidelines.

The panelists endorsed that: (1) treatment(s) for GERD should not be used when there are no clinical features of GERD; and (2) pediatric GERD guidelines should be used to guide treatment and investigations.

To improve understanding of the interrelatedness of airway and esophageal diagnoses by evaluating the yield of procedural and radiographic testing of the gastrointestinal tract in children with airway conditions by their referring diagnoses in a pediatric aerodigestive clinic.

A retrospective chart review of all 325 patients seen in the aerodigestive program from 2010 to 2013 was performed in a single academic medical center. Demographics and results from esophagogastroduodenoscopies with biopsies (EGD), upper gastrointestinal fluoroscopy studies (UGI), and pH multichannel intraluminal impedance probe (pH-MII) performed within 30 days of the clinic visit were evaluated according to presenting diagnoses.

Mean patient age was 3.15 years (range 0.15-24 years) and 41.2% were born premature. 189/325 (58.1%) were on acid suppression. A total of 295 EGD, 193 pH-MII, and 54 UGI were performed. The most common diagnosis with an abnormal pH-MII was asthma. The most common diagnoses with an abnormal EGD were feeding difficulty and tracheal esophageal fistula/ esophageal atresia (TEF/EA). EGDs were normal in 188/295 (63.7%), while 39/295 (13.2%) demonstrated esophagitis, and 22/295 (7.5%) had >15 esophageal eosinophils per high power field. The majority of pH-MII (144/193 [74.6%]) and UGI (47/54 [87%]) were normal.

Children with feeding difficulty, TEF/EA, and asthma were the mostly likely to have a histologic abnormality on EGD or an abnormal pH-MII. The majority of children were previously prescribed acid suppression medication and had a referring diagnosis of gastroesophageal reflux disease but were subsequently found to have normal evaluation. Prospective studies are needed to optimize care of this population.

Gastro-oesophageal reflux disease (GORD) is a complex problem in children. Suspected respiratory manifestations of GORD, such as asthma, chronic cough and laryngitis, are commonly encountered in the paediatric practice, but continue to be entities with more questions than answers. The accuracy of diagnostic tests (ie, pH or pH-impedance monitoring, laryngoscopy, endoscopy) for patients with suspected extraoesophageal manifestations of GORD is suboptimal and therefore whether there is a causal relationship between these conditions remains largely undetermined. An empiric trial of proton pump inhibitors can help individual children with undiagnosed respiratory symptoms and suspicion of GORD, but the response to therapy is unpredictable, and in any case what may be being observed is spontaneous improvement. Furthermore, the safety of these agents has been called into question. Poor response to antireflux therapy is an important trigger to search for non-gastro-oesophageal reflux causes for patients' symptoms. Evidence for the assessment of children with suspected extraoesophageal manifestations of GORD is scanty and longitudinal studies with long-term follow-up are urgently required.

This document serves as an update of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2009 clinical guidelines for the diagnosis and management of gastroesophageal reflux disease (GERD) in infants and children and is intended to be applied in daily practice and as a basis for clinical trials. Eight clinical questions addressing diagnostic, therapeutic and prognostic topics were formulated. A systematic literature search was performed from October 1, 2008 (if the question was addressed by 2009 guidelines) or from inception to June 1, 2015 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Clinical Trials. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to define and prioritize outcomes. For therapeutic questions, the quality of evidence was also assessed using GRADE. Grading the quality of evidence for other questions was performed according to the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) and Quality in Prognostic Studies (QUIPS) tools. During a 3-day consensus meeting, all recommendations were discussed and finalized. In cases where no randomized controlled trials (RCT; therapeutic questions) or diagnostic accuracy studies were available to support the recommendations, expert opinion was used. The group members voted on each recommendation, using the nominal voting technique. With this approach, recommendations regarding evaluation and management of infants and children with GERD to standardize and improve quality of care were formulated. Additionally, 2 algorithms were developed, 1 for infants <12 months of age and the other for older infants and children.

The evaluation of symptom association between gastroesophageal reflux and cardiorespiratory events in preterm infants remains unclear. This paper describes a conservative approach to decision-making of anti-reflux surgery through symptom association analysis.

Forty-three neonates with potentially reflux-related cardiorespiratory symptoms underwent synchronized esophageal impedance-pH and cardiorespiratory monitoring. Three indices were considered to evaluate symptom association, the symptom index (SI), the symptom sensitivity index (SSI) and the symptom association probability (SAP). A conservative strategy was adopted regarding the decision of anti-reflux surgery, and therefore, patients were scheduled for laparoscopic Nissen fundoplication if the three indices showed a positive assessment of symptom association. Retrospectively, these indices and the binomial symptom index (BSI) were contrasted against the decision of anti-reflux surgery using different windows of association.

Thirteen patients showed positive symptom association but only two underwent anti-reflux surgery. The SI and the SSI showed an increasing trend with the width of the window of association. The SAP was affected randomly by slightly altering the windowing parameters. The BSI showed the best performance with the two-minute window (κ =0.78) CONCLUSIONS: The pathology under study is known to improve with maturity. However, the severity of cardiorespiratory symptoms may threaten the neonate's life and therefore, in some occasions, invasive treatments must be considered to protect life. The BSI provides a good prediction of a combination of positive SI, SSI and SAP, which may improve clinical decisions. However, further clinical studies are required to prove the BSI as an optimal predictor of clinical outcomes.

Despite the frequency with which antireflux procedures are performed, decisions about gastroesophageal reflux disease treatment remain challenging. Several factors contribute to the difficulties in managing gastroesophageal reflux. First, the distinction between physiologic and pathologic gastroesophageal reflux (gastroesophageal reflux disease-GERD) is not always clear. Second, measures of the extent of gastroesophageal reflux often poorly correlate to symptoms or other complications attributed to reflux in infants and children. A third challenge is that the outcome of antireflux procedures, predominately fundoplications, are relatively poorly characterized. All of these factors contribute to difficulty in knowing when to recommend antireflux surgery. One of the manifestations of the uncertainties surrounding GERD is the high degree of variability in the utilization of pediatric antireflux procedures throughout the United States. Pediatric surgeons are frequently consulted for GERD and fundoplication, uncertainties notwithstanding. Although retrospective series and anecdotal observations support fundoplication in some patients, there are many important questions for which sufficient high-quality data to provide a clear answer is lacking. In spite of this, surgeons need to provide guidance to patients and families while awaiting the development of improved evidence to aid in these recommendations. The purpose of this article is to define what is known and what is uncertain, with an emphasis on the most recent evidence.

Gastroesophageal reflux is common but remains a controversial disease to diagnose and treat and little is known about the role of reflux testing in predicting clinical outcomes, particularly in children at risk for extraesophageal reflux complications. The aim of this study was to determine if rates of hospitalization were affected by reflux burden even after adjusting for aspiration risk.

We prospectively recruited, between 2009 and 2014, a cohort of pediatric patients with suspected extraesophageal reflux disease who were referred for reflux testing and underwent both multichannel intraluminal impedance with pH (pH-MII) and modified barium swallow studies. A subset of patients also underwent bronchoalveolar lavage with pepsin analysis. We determined their rates of hospitalization for a minimum of 1 year following pH-MII testing.

We prospectively enrolled 116 pediatric patients who presented for care at Boston Children's Hospital and underwent both pH-MII and modified barium swallow studies. There was no statistically significant relationship between reflux burden measured by pH-MII or bronchoalveolar pepsin and total number of admissions or number of admission nights even after adjusting for aspiration status (P > 0.2). There were no statistically significant relationships between reflux burden by any method and the number or nights of urgent pulmonary admissions before or after adjusting for aspiration risk (P > 0.08).

Even in aspirating children, reflux burden did not increase the risk of hospitalization. Based on these results, routine reflux testing cannot be recommended even in aspirating children, because the results do not impact clinically significant outcomes.

Heartburn is among the most common gastrointestinal symptoms presenting to both generalist physicians and gastroenterologists. Heartburn that does not respond to traditional acid suppression is a diagnostic and therapeutic dilemma. In the era of high utilization of proton pump inhibitors, a substantial proportion of patients presenting to the gastroenterologist with chronic symptoms of heartburn do not have a reflux-mediated disease. Subjects without objective evidence of reflux as a cause of their symptoms have "functional heartburn". The diagnostic role of endoscopy, reflux and motility testing in functional heartburn (FH) patients is discussed. Lifestyle modifications, pharmacological interventions, and alternative therapies for FH are also presented. Recognition of patients with FH allows earlier assignment of these patients to different treatment algorithms, which may allow greater likelihood of success of treatment, diminished resource utilization and improved quality of life. Further data on this large and understudied group of patients is necessary to allow improvement in treatment algorithms and a more evidence-based approach to care of these patients.

One of the primary indications for reflux testing with multichannel intraluminal impedance with pH (pH-MII) is to correlate reflux events with symptoms such as cough. Adult and pediatric studies have shown, using cough as a model, that patient report of symptoms is inaccurate. Unfortunately, intraesophageal pressure recording (IEPR) to record coughs is more invasive which limits its utility in children. The primary aim of this study was to validate the use of acoustic cough recording (ACR) during pH-MII testing.

We recruited children undergoing pH-MII testing for the evaluation of cough. We simultaneously placed IEPR and pH-MII catheters and an ACR device in each patient. Each 24 h ACR, pH-MII, and IEPR tracing was scored by blinded investigators. Sensitivities for each method of symptom recording were calculated.

A total of 2698 coughs were detected; 1140 were patient reported PR, 2425 were IEPR detected, and 2400 were ACR detected. The sensitivity of PR relative to ACR was 45.9% and the sensitivity of IEPR relative to ACR was 93.6%. There was strong inter-rater reliability (κ = 0.78) for the identification of cough by ACR.

Acoustic recording is a non-invasive, sensitive method of recording cough during pH-MII testing that is well suited for the pediatric population.