title: Esophageal sensitivity to acid in patients with Barrett's esophagus is not related to preserved esophageal mucosal integrity.
abstract: BACKGROUND
  Patients with Barrett's esophagus (BE) usually have severe gastroesophageal reflux. However, they often have surprisingly few reflux symptoms. We hypothesized that BE patients are less sensitive to acid than gastroesophageal reflux disease (GERD) patients without Barrett and that this is due to an unusual preservation of mucosal integrity of the squamous epithelium prohibiting transepithelial acid diffusion.
  
  
  METHODS
  We prospectively analyzed esophageal sensitivity and esophageal mucosal integrity in GERD patients with and without BE and healthy subjects. An acid perfusion test was performed and mucosal integrity was assessed in vivo by electrical tissue impedance spectroscopy and ex vivo by Ussing chamber experiments with biopsy specimens.
  
  
  RESULTS
  Gastroesophageal reflux disease patients with BE were less sensitive to acid than GERD patients without BE, but more sensitive to acid than healthy controls (time to perception Barrett's 14.0 minutes, GERD 4.6 minutes, controls 17.5 minutes). However, extracellular impedance (6.2 and 5.7 vs 8.4×103Ω/m) and transepithelial resistance (94.0 and 89 vs 118 Ω/cm2) was similar in BE and GERD patients and significantly lower than in healthy subjects. Transepithelial fluorescein flux was equally increased in GERD patients with and without BE (1.6 and 1.7×103vs 0.6×103nmol/cm2/h).
  
  
  CONCLUSIONS
  Esophageal hypersensitivity to acid is less pronounced in BE patients than in GERD patients without Barrett. However, mucosal integrity of the squamous epithelium is equally impaired in GERD patients with and without Barrett, indicating that factors other than esophageal mucosal barrier integrity explain the difference in acid sensitivity between those with BE and those without.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P W
authors.identifier: http://orcid.org/0000-0002-0603-934X
authors.initials: PW
authors.lastname: Weijenborg
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: A J P M
authors.initials: AJPM
authors.lastname: Smout
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: K K
authors.initials: KK
authors.lastname: Krishnadath
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J G H M
authors.initials: JGHM
authors.lastname: Bergman
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Verheij
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bredenoord
mesh_terms: D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000503:physiopathology*; D000071041:Esophageal Mucosa / Q000503:physiopathology*; D004947:Esophagus / Q000503:physiopathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
keywords: Barrett; esophagus; mucosal integrity