Juice Test for Identification of Nonerosive Reflux Disease in Heartburn Patients.

BACKGROUND/AIMS: Evaluation of esophageal clearance by orange juice swallowing could be useful to identify different categories of gastroesophageal reflux disease. We determined whether a juice test at the beginning of esophageal pH monitoring can identify nonerosive reflux disease (NERD) among heartburn patients. METHODS: Multiple swallows of orange juice (pH 3) were performed at the beginning of esophageal pH monitoring in 71 heartburn patients off acid-suppressive therapy. The area between pH drop below 5 and recovery to 5 was calculated from pH tracings and named Delta5 (mmol∙L⁻¹âˆ™sec). Fifteen healthy subjects served to determine Delta5 cutoff (95th percentile). Patients were classified as NERD, non-NERD (a mix of reflux hypersensitivity, functional heartburn, and undetermined), and erosive disease depending on acid exposure, reflux symptom analysis, and upper endoscopy. RESULTS: Delta5 cutoff in healthy subjects was 251 mmol·L⁻¹âˆ™sec. Among 71 patients, 23 had NERD, 26 had non-NERD, and 22 had erosive disease. Compared to non-NERD, Delta5 was higher in both NERD (median [interquartile range]: 316 [213-472] vs 165 [105-225]; P ＜ 0.01) and erosive disease (310 [169-625] vs 165 [105-225]; P ＜ 0.01). An elevated Delta5 (＞ 251 mmol∙L⁻¹âˆ™sec) showed sensitivity of 74% and specificity of 81% for identification of NERD. Positive and negative likelihood ratios were 3.84 and 0.32 respectively, whereas test accuracy was 78%. CONCLUSIONS: A juice test with calculation of Delta5 helps in the identification of true NERD among heartburn patients with endoscopy-negative reflux disease. In these patients, an elevated Delta5 could make prolonged reflux testing unnecessary.

The Prevalence of Rome IV Nonerosive Esophageal Phenotypes in Children.

OBJECTIVES: To assess the prevalence of Rome IV nonerosive esophageal phenotypes in children using multichannel intraluminal impedance testing and to describe the rates of proton pump inhibitor (PPI) responsiveness and the frequency of microscopic esophagitis in these patients. STUDY DESIGN: We conducted a retrospective review of all children ≥5 years of age who underwent esophagogastroduodenoscopy and multichannel intraluminal impedance testing off PPI therapy for evaluation of typical gastroesophageal reflux symptoms. Only children with symptoms during the multichannel intraluminal impedance testing were included. Children were categorized into the following nonerosive esophageal phenotypes using Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and functional heartburn. Rates of esophagitis and responsiveness to acid suppression therapy were assessed. RESULTS: Forty-five children were included: 27% were categorized as having nonerosive reflux disease, 29% with reflux hypersensitivity (27% acid and 2% nonacid), and 44% with functional heartburn. Older children reported significantly more heartburn (P < .001) than younger children, whereas younger children were more likely to report nonspecific pain (P = .047). There were no differences between groups in other reflux symptoms, rates of responsiveness to PPIs, or the presence of microscopic esophagitis on biopsy. CONCLUSIONS: Functional heartburn is the most common Rome IV nonerosive esophageal phenotype in children. Neither microscopic esophagitis nor PPI responsiveness can predict phenotype in pediatric patients.

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity.

Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD.NEW & NOTEWORTHY In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder.