Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease

Abstract

Background and Objective: Weakly acidic reflux reaching to the proximal esophagus is closely related to the perception of gastroesophageal reflux in patients with nonerosive reflux disease despite treatment with a proton pump inhibitor (PPI). However, little is known about the involvement of the patients’ mucosal integrity of the proximal esophagus. Methods: We recruited 15 symptomatic nonerosive gastroesophageal reflux disease (GERD) patients with a positive symptom index despite PPI treatment and 11 healthy asymptomatic volunteers as controls. The biopsy specimens obtained from the proximal and distal esophagus were applied to a mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) against a pH 4 weak acid. The esophageal biopsy samples were subjected to quantitative real-time PCR and immunohistochemical analysis. Results: In the proximal esophagus, the weak acid exposure reduced the TEER in the PPI-refractory patients compared to that in the controls. The frequency of the reflux extending to the proximal esophagus had a significant correlation with the reduction in the proximal esophageal TEER in the patients. The reduced TEER in the proximal esophagus was accompanied by an increase in IL-8 and IL-1β mRNA and a decrease in occludin mRNA levels. The proximal esophageal mucosa in the patients presented infiltration of CD3-positive lymphocytes and an increased expression of solute carrier organic anion transporter family member 2A1 (SLCO2A1), a passage gate of reflux symptom-evoking molecules. Conclusions: The reflux perception is related to an impairment of the proximal esophageal mucosal integrity in patients with nonerosive reflux disease despite PPI.

Efficacy of esophagus protection in complex treatment of erosive gastroesophageal reflux disease: a systematic review and meta-analysis of controlled trials

“…Стоит отметить, что данные о высокой эффективности применения комбинации ИПП и Альфазокса при купировании изжоги неоднократно показаны в исследованиях на популяциях пациентов с НЭРБ [28]. Данный факт, вероятно, свидетельствует о том, что в основе генеза изжоги при НЭРБ и эрозивной форме ГЭРБ могут лежать различные механизмы [29,30].…”

Chitosan Nanoparticles for Gastroesophageal Reflux Disease Treatment

“…Although prucalopride has demonstrated safety regarding cardiac issues, further clinical trials are needed to determine its efficacy in treating GERD [ 65 ]. In some cases, heartburn-like symptoms unrelated to reflux can be caused by psychological stress or esophageal muscle disorders, leading to a diagnosis of functional heartburn instead of GERD, even with negative results on symptom tests and PPI use [ 70 ].…”

The Impact of Duodenal Mucosal Vulnerability in the Development of Epigastric Pain Syndrome in Functional Dyspepsia

“…We used an electrophysiological measurement of TEER to evaluate duodenal mucosal barrier function using a mini-Ussing chamber system (EM-CYSY-2 Ussing Chamber Sytems, Physiologic Instruments, CA, USA) and a 2-channel voltage clamp with a preamplifier system (EVC4000-2, Physiologic Instruments), as previously reported [27]. In brief, duodenal biopsy samples were placed on a tissue mounting slide (Ussing Slider P2308, Physiologic Instruments) that has a 1 mm diameter circular aperture (area = 0.0079 cm 2 ).…”