Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis

Background/AimsEsophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment. MethodsNinety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (nonerosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twicedaily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients. ResultsThe intercellular spaces were dilated in both EE and NERD patients (P < 0.05). The value 0.73 mm could be used as the cut-off DIS value to distinguish patients from controls (area under the curve [AUC] = 0.849, P < 0.01). One thousand seven hundred sixty-four ohms could be used as the cut-off impedance values to distinguish patients from controls (AUC = 0.794, P < 0.01). The baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time (r = -0.527, P < 0.05). There was a weak correlation between DIS and baseline impedance (r = -0.230, P < 0.05). "Baseline impedance > 1764 Ω" was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P < 0.01). ConclusionsThe DIS and decreased baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.

Section: Intercellular Space Measurement Under Transmission Electron mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment

Xie

Sifrim

et al. 2018

“…21 Sensory neurons in the esophageal epithelium reside within the intercellular spaces; thus, an increase in paracellular permeability can potentially explain the presence of heartburn symptoms during esophageal acid exposure in patients with NERD. 21 Weijenborg et al 22 also demonstrated that compared with healthy volunteers, patients with GERD are more sensitive to acid. This occurrence is related to the damage to esophageal mucosal integrity.…”

Section: Discussionmentioning

confidence: 98%

Relationship Between Salivary Pepsin Concentration and Esophageal Mucosal Integrity in Patients With Gastroesophageal Reflux Disease

Sifrim

Xie

et al. 2017

Background/AimsIncreased salivary pepsin could indicate an increase in gastro-esophageal reflux, however, previous studies failed to demonstrate a correlation between salivary pepsin concentrations and 24-hour esophageal acid exposure. This study aims to detect the salivary pepsin and to evaluate the relationship between salivary pepsin concentrations and intercellular spaces (IS) in different gastroesophageal reflux disease phenotypes in patients. MethodsA total of 45 patients and 11 healthy volunteers were included in this study. All subjects underwent upper gastrointestinal endoscopy, 24-hour ambulatory multichannel impedance-pH (MII-pH) monitoring, and salivary sampling at 3-time points during the 24-hour MII-pH monitoring. IS were measured by transmission electron microscopy, and salivary pepsin concentrations were determined by enzyme-linked immunosorbent assay. ResultsThe IS measurements were greater in the esophagitis (EE), non-erosive reflux disease (NERD), and hypersensitive esophagus (HO) groups than in the functional heartburn (FH) and healthy volunteer groups, and significant differences were indicated. Patients with NERD and HO had higher average pepsin concentrations compared with FH patients. A weak correlation was determined between IS and salivary pepsin among patients with NERD (r = 0.669, P = 0.035). ConclusionsWe confirmed the presence of a higher level of salivary pepsin in patients with NERD than in patients with FH. Salivary pepsin concentrations correlated with severity of mucosal integrity impairment in the NERD group. We suggest that in patients with NERD, low levels of salivary pepsin can help identify patients with FH, in addition the higher the pepsin concentration, the more likely the severity of dilated IS.

“…We believe that the lower baseline impedance indicates impaired mucosal integrity, which would allow faster ion (ie, acid) transfer across the cell membrane to reach acid receptors. 68 The resulting acid hypersensitivity could possibly explain the increased swallowing rate and faster acid clearance in patients with BE. The paradoxical findings of concurrent longer ambulatory acid exposure time in patients with BE despite shorter acid clearance time during the random acid clearance test need an explanation.…”

Section: Discussionmentioning

confidence: 99%

Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett‘s Esophagus Than in Healthy Controls

Lottrup

Krarup

Gregersen

et al. 2016

Background/AimsImpaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett's esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett's esophagus to that in healthy controls. MethodsA total of 26 patients with histology-confirmed Barrett's esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. ResultsCompared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pHmeasurement and acid clearance test were not correlated (all P > 0.3). ConclusionsMore frequent swallowing and thus faster acid clearance in Barrett's esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes.