Concurrent Celiac Disease and Eosinophilic Esophagitis in a Pediatric Cohort: More Than a Coincidence.

Celiac disease (CeD) and eosinophilic esophagitis (EoE) are immune-mediated disorders that can occur in the same patient. A retrospective study at a tertiary care hospital was conducted to determine the prevalence of EoE in a pediatric population with CeD and to compare characteristics of patients with both diseases to patients with CeD-only. Among the 148 patients with CeD identified in the study, 11 patients had both CeD and EoE (7.4%). Patients with both CeD and EoE had a higher absolute eosinophil count (per µL) at diagnosis compared to patients with CeD-only (454.1 ± 122.7 vs 231.9 ± 19.4, P = .003). In conclusion, there was a higher proportion of EoE in patients with CeD than would be expected in the general population, suggesting a potential pathophysiological overlap between the 2 diseases. An elevated peripheral absolute eosinophil count may help predict which patients with CeD may additionally have EoE.

Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study.

BACKGROUND: Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD. METHODS: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort. Children (aged 0-18 years) with IBD who had commenced vedolizumab were followed up at baseline and at 2, 6, and 14 weeks. Children were managed according to local prescribing practices without standardisation of dosing or criteria for escalation, but the study protocol suggested dosing of 177 mg/m2 body surface area (up to 300 mg maximum). The primary outcome was steroid-free and exclusive enteral nutrition-free remission at 14 weeks, analysed according to the intention-to-treat principle. Serum samples were taken for analysis of drug concentration and faecal calprotectin at baseline, and at 2, 6, and 14 weeks. Adverse events were recorded in real time and classified as severe or non-severe and related or unrelated to vedolizumab. This study is registered with ClinicalTrials.gov, NCT02862132. FINDINGS: Between May 19, 2016, and April 1, 2022, 142 children (76 [54%] girls and 66 [46%] boys; mean age 13·6 years [SD 3·6]) were enrolled. 65 (46%) children had Crohn's disease, 68 (48%) had ulcerative colitis, and nine (6%) had unclassified IBD (those with unclassified IBD were analysed with the ulcerative colitis group). 32 (42% [95% CI 30-54]) of 77 children with ulcerative colitis and 21 (32% [23-45]) of 65 children with Crohn's disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks. Median drug concentrations at week 14 were higher in children with ulcerative colitis than in those with Crohn's disease (11·5 µg/mL [IQR 5·5-18·1] vs 5·9 µg/mL [3·0-12·7]; p=0·006). In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 µg/mL at week 14 (area under the curve 0·69 [95% CI 0·41-0·98]), corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg. 32 (23%) of 142 children reported at least one adverse event, the most common were headache (five [4%]), myalgia (four [3%]), and fever (three [2%]). None of the adverse events were classified as severe, and only two (1%) patients discontinued treatment due to adverse events. INTERPRETATION: Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis. Vedolizumab should be considered in children when other approved drug interventions for IBD are unsuccessful. In children who weigh less than 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/m2) or weight (10 mg/kg). FUNDING: The European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.

Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach.

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.

Effect of a gluten-free diet on albuminuria in children with newly diagnosed celiac disease.

BACKGROUND AND OBJECTIVES: Altered gastrointestinal permeability in celiac disease (CD) is mediated by zonulin. The receptor for zonulin is expressed on podocytes. Therefore, we tested the effect of a gluten-free diet (GFD) on albuminuria in pediatric patients with newly diagnosed CD. METHODS: We performed a cohort study comparing urinary albumin (µg):creatinine (mg) ratio (ACR) in CD patients vs controls and in response to a GFD. RESULTS: Children with CD (n=46) had higher ACR compared to controls (n=21), 20.2±5.6 versus 8.4±1.1 µg/mg, P=0.16 and exceeded 30 µg/mg (microalbuminuria cut-off) in 7/46 cases. 17 patients had a follow-up assessment (interval 6.1±0.7 months) on a GFD. Baseline ACR was 20.7±5.2 that fell to 10.4±1.5 µg/mg, P=0.035. CONCLUSION: Children and adolescents with newly diagnosed CD have low-grade albuminuria that is numerically higher than controls and that declined after implementation of a GFD. CD may be associated with reversible defects in the glomerular barrier.

Integrating Suicide Risk Screening into Pediatric Ambulatory Subspecialty Care.

BACKGROUND: Suicide risk screening is recommended in pediatric care. To date, no previous studies illustrate the implementation of suicide risk screening in pediatric subspecialty care, even though chronic medical conditions are associated with a higher risk of suicide. METHODS: A large multidivision pediatric ambulatory clinic implemented annual suicide risk screening. Patients ages 9-21 years participated in suicide risk screening using the Ask Suicide-Screening Questions during the project. A multidisciplinary team employed quality improvement methods and survey-research design methods to evaluate the feasibility and acceptability of the screening process for patients, families, and medical providers. RESULTS: During the quality improvement project period, 1,934 patients were offered screening; 1,301 (67.3%) patients completed screening; 82 patients (6.3% of 1,301 patients) screened positive. The monthly compliance rate held steady at 86% following several Plan-Do-Study-Act cycles of improvement. The survey results demonstrate that providers rated the suicide risk screening process positively; however, a subset of providers indicated that the screening process was out of their scope of practice or impeded their workflow. CONCLUSIONS: Suicide risk screening is feasible in pediatric specialty care and can identify at-risk patients. Continued efforts are needed to standardize suicide risk screening practices. Future directions include identifying factors associated with suicide risk in patients in pediatric subspecialty care settings.

Persistent organic pollutant exposure and celiac disease: A pilot study.

Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.

Airway and esophageal eosinophils in children with severe uncontrolled asthma.

AIM: Children with severe uncontrolled asthma (SUA) have a high burden of symptoms and increased frequency of asthma exacerbations. Reflux esophagitis and eosinophilic esophagitis are important co-morbid factors for SUA. Both are associated with the presence of eosinophils in esophageal mucosa. We hypothesized that esophageal eosinophils are frequently present and correlate with the presence of airway eosinophils in children with SUA. METHOD: We performed a retrospective analysis of a prospective database of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy [EsB]) at our Aerodigestive Center for evaluation of SUA. Children with known cystic fibrosis, primary ciliary dyskinesia, and aspiration-related lung disease were excluded. RESULT: Twenty-four children (21 males) ages 2-16 years were studied. Elevated BAL eosinophils were found in 10 (42%) patients, endobronchial eosinophils in 16 (67%); 7 (29%) had endobronchial eosinophils without elevated BAL eosinophils. Esophageal eosinophils were found in 11 (46%) patients. There was a correlation between the amount of eosinophils in BAL and EBB (R = 0.43, P = 0.05) airway eosinophils, defined as elevated BAL and/or EBB eosinophils, correlated with esophageal eosinophils (R = 0.41, P = 0.047). CONCLUSION: We concluded that airway and esophageal eosinophils are frequently present in children with SUA.

Aerodigestive dysbiosis in children with chronic cough.

In pediatric patients with chronic cough, respiratory culture techniques commonly yield negative results. Studies using culture-independent methods have found a high relative abundance of oral microbes in the lower airways, suggesting that the topographical continuity, and dynamics of the intraluminal contents of the aerodigestive system likely influence the lower airway microbiota. We hypothesize that in subjects with chronic cough, clinical diagnosis will correlate with distinct microbial signatures detected using culture-independent methods. STUDY DESIGN AND METHODS: We enrolled 36 pediatric subjects with chronic cough in a cross-sectional study. Subjects were categorized into four clinical groups: asthma, bacterial bronchitis, neurologically impaired-orally fed, and neurologically impaired enterally fed. Samples from the aerodigestive tract were obtained through bronchoscopy and upper endoscopy. 16S rRNA gene sequencing compared the microbiota from bronchoalveolar lavage (BAL), tracheal, supraglottic, esophageal, gastric, and duodenal samples. RESULTS: We observed that the lower airway microbiota of asthma subjects had higher α diversity as compared with the other groups. ß diversity analysis of BAL samples revealed significant differences between the groups. Among the taxonomic differences found, most differentially enriched taxa were upper airway organisms such as Rothia, Gemellaceae (u.g. or uncharacterized genus), and Granulicatella in asthma, Prevotella in bacterial bronchitis, and Veillonella in neurologically impaired orally fed subjects. Greater dissimilarity between the upper airway and lower airway microbiota was associated with increased neutrophilic airway inflammation. CONCLUSIONS: Distinct dysbiotic signatures can be identified in the lower airway microbiota of pediatric subjects with chronic cough that relates to the degree and type of inflammation.

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.

BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.

Using the Objective Structured Clinical Examination to Assess ACGME Competencies in Pediatric Gastroenterology Fellows.

BACKGROUND: The Accreditation Council for Graduate Medical Education has described 6 core competencies with which trainees should demonstrate proficiency. Using the Objective Structured Clinical Examination (OSCE), we aimed to assess 4 of these competencies among Pediatric Gastrointestinal (GI) fellows (PGs). METHODS: Eight first-year PGs from 6 medical centers in the New York area participated in a 4-station OSCE with trained standardized patient (SP) actors. The cases included an emergency department (ED) consult, or "ED Consult" for lower gastrointestinal bleeding; "Breaking Bad News" focusing on CF nutritional complications; "Second Opinion" for abdominal pain; "Transition of Care" for inflammatory bowel disease. At each station, attending faculty observed the encounters behind a 1-way mirror. SPs and faculties provided immediate feedback to the examined fellows. Previously validated OSCE checklists were used to assess performance. On completion, fellows attended debriefing sessions and completed surveys about the educational value. RESULTS: Median overall milestone competency scores were 6.9 (PC1), 4.8 (PC2), 5.9 (MK1), 5.7 (MK2), 6.4 (ICS1), 6.9 (Prof1), and 6.7 (Prof3). Overall, fellows score highest (7/9) on the inflammatory bowel disease "Transition of Care" case, found the "Breaking Bad News" Cystic Fibrosis OSCE to be the most challenging, and were most comfortable with the "ED Consult" OSCE, as a commonly encountered scenario. Overall, the fellows rated the educational value of the program highly. CONCLUSIONS: To our knowledge, although the OSCE has been validated in other medical fields, this is the first OSCE program developed for PGs fellows. These OSCEs have included Accreditation Council for Graduate Medical Education competencies, serving to assess fellows' skills in these areas while exposing them to challenging medical and psychosocial cases that they may not frequently encounter.

The impact of immune dysregulation on the development of autoimmune gastrointestinal and liver disease.

The intestinal epithelium plays an active immunologic role in preventing the uptake of foreign antigens. Additionally, the intestinal mucosa is an active site for immune suppression through the development of oral tolerance. Dysfunction of any aspect of the intestinal barrier, such as impairment of intestinal tight junctions, immunologic dysregulation or decreased oral tolerance will lead to overstimulation of the immune system upon exposure to foreign antigens and subsequent unregulated chronic intestinal inflammation. This persistent inflammatory activity may potentially predispose the patient to the development of intestinal autoimmune disease. An active immune response possibly directed against intestinal flora has been postulated to be the underlying etiology for inflammatory bowel disease. Failure of oral tolerance is thought predispose a patient to celiac disease and possibly eosinophilic esophagitis. Additionally, an active immunologic response to absorbed antigen may be the underlying etiology for the development of autoimmune liver disease.

Autoimmune hepatitis: a classic autoimmune liver disease.

AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.

Inflammatory bowel disease: the classic gastrointestinal autoimmune disease.

Inflammatory bowel disease (IBD) is an idiopathic disease thought to be caused by a dysregulated immune response to host intestinal microflora. The role of genetic factors is indicated by familial clustering of cases and higher incidence in monozygotic twins. An interaction between genetic and environmental factors is thought to play a role in the pathogenesis of these disorders. Changes in diet, antibiotic use and intestinal colonization have likely contributed to increased prevalence of inflammatory bowel disease in the past century. Environmental factors or infections are thought to alter the barrier function of the epithelium, leading to loss of immune tolerance to intestinal antigens. This loss of tolerance activates dendritic cells, triggering their transport to mesenteric lymph nodes, where they promote differentiation of naïve T cells to TH-1, TH-2, TH-17 cells or T regulatory cells. Production of proinflammatory cytokines and chemokines then follows. Circulating effector and regulatory cells enter the intestine through a highly selective mechanism that involves interaction with the vascular endothelium, diapedesis through the vessel wall and migration to the lamina propria. There are several genes implicated in IBD. Mutations in certain genes can cause defective down regulation of the innate immune response, ineffective clearance of intracellular bacteria and proliferation of both luminal and mucosal-adherent commensal bacteria. IBD is a chronic relapsing inflammatory condition that is immune mediated. Results from research in animal models, human genetics, basic science and clinical trials provide evidence that it is heterogeneous, characterized by various genetic abnormalities, leading to a dysregulated and overly aggressive T cell response to commensal enteric bacteria. Different genetic abnormalities can be characterized as causing defects in mucosal barrier function, immunoregulation or bacterial clearance. Advances in our understanding of the interplay between components of innate and adaptive immune response will be central to future progress.

Eosinophilic esophagitis: an autoimmune esophageal disorder.

Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal inflammatory disease associated with esophageal dysfunction resulting from severe inflammation. The incidence and prevalence of EoE have been increasing in the past decade; however, the reason for this increase is unclear. There is a chronic inflammatory infiltrate that is present in EoE which promotes inflammation, symptoms, and dysfunction. In addition to eosinophils, interleukin (IL)-5 expressing T cells, B cells, eotaxin-3, IL-13, and IgE-bearing mast cells are present in EoE and are thought to contribute to the disease process. Eosinophils are pro-inflammatory and modulate multiple aspects of the immune response. Eosinophils produce a wide range of inflammatory cytokines, chemokines, granulocyte-monocyte colony-stimulating factors, and tumor necrosis factors. Once activated, eosinophils release granule components, which are toxic to a variety of tissues. Transforming growth factor ß1 is a pro-fibrotic molecule produced by epithelial and inflammatory cells, is overexpressed in EoE, and plays a role in esophageal remodeling. Fibrous remodeling in EoE could be associated with symptoms of dysphagia and may explain and predict future esophageal strictures and dysmotility. EoE is a complex disease involving multiple activation pathways, a large number of cells, and various inflammatory molecules. It, along with other atopic disease, is becoming increasingly prevalent and has an important genetic load and may represent as an immunological tolerance disorder of the GI tract.

Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.

Simultaneous development of ulcerative colitis in the colon and sigmoid neovagina.

Vaginoplasty using sigmoid colon is a common technique for creation of a neovagina. However, special consideration must be given to potential long term consequences of using a colonic conduit for vaginal replacement. We report on the youngest described case in which a patient developed ulcerative colitis refractory to medical therapy with simultaneous involvement of a sigmoid neovagina requiring total proctocolectomy and neovaginectomy. A 17 year old XY female with a history of gonadal dysgenesis and sigmoid graft vaginoplasty presented with a history of bloody, mucoid vaginal discharge, abdominal pain, bloody diarrhea and weight loss. Colonic and neovaginal biopsies demonstrated active colitis with diffuse ulcerations, consistent with ulcerative colitis. Despite aggressive immunosuppressive treatment she had persistent neovaginal and colonic bleeding requiring multiple transfusions, subtotal colectomy and ultimately completion proctectomy and neovaginectomy. It is imperative to recognize that colectomy alone may be an inadequate surgical intervention in patients with ulcerative colitis and a colonic neovaginal graft and that a concomitant neovaginectomy may be integral in providing appropriate treatment.

Conservative long-term treatment of children with eosinophilic esophagitis.

BACKGROUND: Current treatments of eosinophilic esophagitis (EoE), including restrictive diets or glucocorticoids, provide only transient improvement. Proton pump inhibitor (PPI) use in EoE does not lead to histologic improvement; however, the long-term use of PPI on symptoms and prevention of complications has not been evaluated. OBJECTIVE: To evaluate the use of PPI as maintenance therapy in children with EoE. METHODS: Eosinophilic esophagitis was diagnosed based on initial endoscopic biopsies and persistent eosinophilic inflammation despite PPI therapy. Inclusion criteria included diagnosis of EoE and PPI use as primary maintenance treatment. Patients were excluded if they were treated with dietary or glucocorticoid therapy. Histologic evidence of inflammation as well as degree of subepithelial fibrosis at presentation was compared with most recent biopsies while receiving PPI therapy. RESULTS: Thirty-eight patients (30 males and 8 females; average age 6.7 ± 5.4 years) fulfilled inclusion criteria. Duration of follow-up was 3.0 ± 2.4 years. At presentation, vomiting was significantly more frequent in the younger patients, whereas dysphagia occurred more frequently in the older patients. At follow-up, 26 patients were asymptomatic, and the remaining 12 patients' symptoms were significantly improved. No complications of stricture or food impaction were seen. Significant eosinophilic inflammation persisted in 28 patients. No difference in degree of subepithelial fibrosis at diagnosis compared with most recent biopsies. The z-scores of the treated EoE patients significantly improved. CONCLUSION: Patients with EoE treated with PPIs show an improvement in symptoms and z-scores despite persistent eosinophilic inflammation. PPI treatment may be useful maintenance therapy in children with EoE.

Impedance and extraesophageal manifestations of reflux in pediatrics.

OBJECTIVES/HYPOTHESIS: Extraesophageal manifestations of gastroesophageal reflux (GER) include such signs and symptoms as cough, asthma, respiratory symptoms, hoarseness, and laryngoscopic findings. We reviewed the role of MII-pH monitoring in the evaluation of these findings in children to determine whether there is an association with pathological acid or nonacid reflux. STUDY DESIGN: Retrospective chart review. METHODS: We retrospectively reviewed charts from patients who underwent MII-pH. Inclusion criteria were ages 0 to 21 years with extraesophageal signs or symptom. Data were analyzed using dedicated software and manually reviewed. Reflux composite score was calculated based on DeMeester criteria. Impedance scores were calculated based on adult criteria. Symptom indexes were calculated. RESULTS: A total of 119 MII-pH studies were performed. Of those, 63 studies met inclusion criteria. There were 39 males and 24 females with mean age 7.32 ± 4.1 years. The most common indication was cough. Six children had pathological GER based on DeMeester score. Using impedance criteria, only 10 of 63 patients had an abnormal evaluation (mean reflux episodes 107). Seven patients (15.2%) were found to have an association between symptom and reflux event. CONCLUSIONS: No association was demonstrated between the extraesophageal signs and symptoms and pathological GER based on DeMeester score or the number of reflux events based on impedance testing.