Pathogenesis Of Non-erosive Reflux Disease Research Articles

Study on syndrome rules of stagnated heat in liver and stomach of non-erosive reflux disease based on microecology of tongue coating.

At present, the pathogenesis of non-erosive reflux disease (NERD) is still unclear, and proton pump inhibitors are the main treatment drug. However, the effect is limited. Traditional Chinese medicine treatment of NERD has advantages. Stagnated heat in liver and stomach syndrome is the most important traditional Chinese medicine syndrome type of this disease. Tongue diagnosis is an important basis for the diagnosis of stagnated heat in liver and stomach syndrome. The microecology of tongue coating suggests the occurrence and development of disease. The purpose of this study aims to clarify the regular changes of tongue coating microecology in stagnated heat in liver and stomach syndrome of NERD. This is a cross-sectional clinical trial. This study is divided into NERD stagnated heat in liver and stomach syndrome group, qi stagnation, and phlegm obstruction syndrome control group and normal control group, with 20 cases in each group. Tongue coating samples will be collected from 3 groups, and 16SrRNA gene sequencing technology will be used to detect the genome of tongue coating flora in patients with NERD with stagnated heat in liver and stomach syndrome, control group with qi stagnation and phlegm obstruction syndrome and normal control group. The main outcome measures are the distribution, diversity, and richness of the tongue flora in patients and healthy controls. The results of this study will clarify the internal relationship between NERD stagnated heat in liver and stomach syndrome and the microecological changes in tongue coating.

Oesophagus: Symptom perception in patients with NERD: do nerves matter?

Various mechanisms eliciting symptoms in GERD and its most common phenotypic presentation, nonerosive reflux disease (NERD), have been suspected and investigated. One study now suggests that superficial nerves in the oesophageal epithelium might have a key role in the pathogenesis of NERD and could represent a potential target for topical therapies.

High Expression of Calcitonin Gene-Related Peptide and Substance P in Esophageal Mucosa of Patients with Non-Erosive Reflux Disease

Visceral hypersensitivity is an important etiology of non-erosive reflux disease (NERD). Calcitonin gene-related peptide (CGRP) and substance P (SP) are involved in the sensitization of afferent neuronal pathways. The objectives of this study were to evaluate visceral hypersensitivity in NERD patients, investigate the association between visceral hypersensitivity and mucosal expression of SP and CGRP, and assess their involvement in the pathogenesis of NERD. Twenty-six NERD patients and 12 healthy volunteers were recruited. Intraesophageal balloon distention was performed, and initial perception threshold (IPT) and threshold of discomfort (ToD) were determined. Immunohistochemical staining was used to measure the optical density (OD) of CGRP and SP-reactive levels in esophageal mucosa, and the numbers of CGRP and SP-reactive neural fibers. IPT and ToD were 9.6±4.8 and 12.3±3.2ml, respectively, in NERD patients, significantly lower than for controls (13.2±7.5 and 21.6±5.7ml, P<0.05 and P<0.01, respectively). Mean OD values for CGRP and SP staining were significantly higher in NERD than for controls (both P<0.05) and, in NERD, were negatively correlated with IPT and ToD (all P<0.01). Numbers of CGRP and SP-reactive neural fibers in esophageal submucosa of NERD patients were significantly increased (both P<0.05). Expression of esophageal epithelial CGRP and SP is increased, and correlates negatively with perception thresholds in NERD. These findings may aid understanding of peripheral visceral hypersensitivity and the development of new therapeutic approaches for management of NERD.

Alterations of Mast Cells in the Esophageal Mucosa of the Patients With Non-Erosive Reflux Disease.

BackgroundMast cells (MCs) are widely distributed in the gastrointestinal tract, which could be involved in visceral hypersensitivity and gut dysmotility. Whether esophageal MCs play a role in non-erosive reflux disease (NERD) has yet to be determined. The aim of this study was to characterize esophageal MCs distribution, degranulation, and ultrastructure.MethodsThe esophageal mucosa at 5 cm above the end of esophagus was obtained from 26 NERD and 14 healthy volunteers (control) by gastroscopy. Immunohistochemistry was performed and average MC counts per high-power field (HPF) and the percentage of degranulated MCs were obtained. The ultrastructure of MCs was observed by transmission electron microscope (TEM).ResultsMore MCs were observed in NERD (7.23 ± 2.41 cells/HPF) as compared with controls (3.79 ± 1.67 cells/HPF) (P < 0.01) and the percentage of degranulated MCs in NERD was also significantly higher than controls (26.85 ± 8.79% vs 11.5 ± 4.18%, P < 0.01). Under TEM, more Golgi apparatus, mitochondria and endoplasmic reticulum were found in MCs in patients with NERD. Special secreting particles were also found in cytoplasm, more vacuoles were left after MCs degranulation in patients with NERD.ConclusionsOur results indicate that increased numbers of MCs and MCs activation may be involved in the pathogenesis of NERD.

34 Reflux Esophagitis May Result Primarily from An Immune-Mediated Injury Rather Than from a Caustic, Chemical Injury

Esophageal mucosa dilated intercellular spaces (DIS) is involved in the pathogenesis of nonerosive reflux disease (NERD). Patients with NERD have DIS not only in the reflux-exposed distal esophagus but also in the less exposed proximal esophagus. Luminal acid is very important for development of DIS. However, we recently found that In Vitro exposure of rabbit esophageal mucosa to weakly acidic solutions may also induce DIS. It is known that patients with NERD or GERD “on” PPI may still have esophageal exposure to weakly acidic reflux. We assessed, in healthy human subjects, the effect of esophageal acid and weakly acidic perfusions. Our aim was to study changes in mucosal intercellular spaces (ICS) both in the distal “exposed” and in the proximal “non-exposed” esophagus. Methods: 14 healthy volunteers (7 males, 23±1y) underwent upper GI endoscopy with esophageal biopsies at 3 and 13 cm proximal to the esophago-gastric junction (EGJ). Thereafter, subjects received esophageal perfusions with 3 different solutions in random order (separated 3 weeks). Perfusions (2 ml/min) were performed in sitting position, at 5 cm above the EGJ during 30 min. We used: 1) saline (pH 5.5, weakly acidic), 2) saline at pH 2 plus 0.5 mg/mL pepsin (acidic solution) and 3) acid solution plus 2 mM of glycocholic acid (acidic solution +GC). pH was continuously measured at the biopsy sites (3 and 13 cm above ECJ). Biopsies were taken 10 min after end of perfusion. Electron microscopy was used to measure esophageal mucosa ICS. Results: Endoscopy showed no macroscopic erosions after perfusions. pH measurements confirmed distal esophageal mucosa acidification and no changes in nonexposed proximal esophagus in 10 subjects (4 excluded). As expected, distal esophageal perfusion with acid solutions (with pepsin and/or bile acids) provoked DIS. Interestingly; perfusion with saline solution (pH 5.5) provoked DIS. Not only perfusions provoked DIS in the “exposed” distal area. They also induced DIS in the “non-exposed” proximal esophagus (table).Conclusions: The human esophagus is very sensitive to a 30min continuous exposure to acidic and weakly acidic material. Reflux events (acid or weakly acidic), particularly during supine periods, may provoke similar exposure and induce distal and proximal DIS. The mechanism underlying proximal spread of DIS to non-exposed areas requires further investigation.

The modified glucose clearance test: a novel non‐invasive method for differentiating non‐erosive reflux disease and erosive oesophagitis

Impaired salivary secretion has been reported to cause abnormal acid clearance from the oesophagus in gastro-oesophageal reflux disease (GERD). However, few studies have explained the differences between non-erosive reflux disease (NERD) and erosive oesophagitis (EO) with respect to salivary secretion. Aim To elucidate these differences, we measured salivary secretion by using the modified glucose clearance test (mGCT). All subjects completed endoscopic examinations, the frequency scale for the symptoms of GERD questionnaire and the mGCT comprising a resting GCT (measured as RGC time) and a chewing-stimulated GCT (SGC time). Resting glucose clearance time was 18.5 min in control group and significantly longer in NERD and EO groups (28.5 and 39.0 min respectively). SGC time was 6.1 min in control group and 7.2 min in NERD group and significantly longer in EO group (10.2 min) than in the control and NERD groups. In the EO group, both resting and stimulated salivary secretions were less than in control group. However, in the NERD group, resting salivary secretion was decreased, but stimulated salivary secretion was similar to that of the control group. Therefore, these results may help in explaining the differences in the pathogenesis of NERD and EO.