The mucosal integrity in phenotypes of gastroesophageal reflux disease and functional heartburn

Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) ( P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) ( P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm−2·h−1) than in the proximal segment (368 nmol·cm−2·h−1) ( P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.

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Gastroesophageal reflux disease-related and functional heartburn

Current Opinion in Gastroenterology ◽

10.1097/mog.0000000000000282 ◽

2016 ◽

Vol 32 (4) ◽

pp. 344-352 ◽

Cited By ~ 5

Author(s):

Hiroto Miwa ◽

Takashi Kondo ◽

Tadayuki Oshima

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Functional Heartburn

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965 Differentiation of Gastroesophageal Reflux Disease (GERD) and Functional Heartburn (FH) by Histopathological Changes in Patients With Refractory Heartburn

Gastroenterology ◽

10.1016/s0016-5085(12)60631-3 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-167 ◽

Cited By ~ 2

Author(s):

Arne Kandulski ◽

Doerthe Kuester ◽

Carlos Caro ◽

Jochen Weigt ◽

Thomas Wex ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Histopathological Changes ◽

Functional Heartburn

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00345.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. G323-G329 ◽

Cited By ~ 46

Author(s):

Pim W. Weijenborg ◽

André J. P. M. Smout ◽

Caroline Verseijden ◽

Henk A. van Veen ◽

Joanne Verheij ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Tight Junction ◽

Reflux Disease ◽

Tight Junction Proteins ◽

Acid Sensitivity ◽

Nonerosive Reflux Disease ◽

Mucosal Integrity ◽

Control Subjects ◽

Junction Proteins

Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin.

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