Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease
The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.
A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII–pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.
Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = −0.41, p < 0.001), and a weak but significant correlation (r = −0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = −0.637, p < 0.001) and claudin-1 and the baseline impedance (r = −0.648, p < 0.001).
Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.
- Farre R, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011;60(7):885–92. CrossRef
- Kessing BF, et al. Esophageal acid exposure decreases intraluminal baseline impedance levels. Am J Gastroenterol. 2011;106(12):2093–7. CrossRef
- Tobey NA, et al. Dilated intercellular spaces and shunt permeability in nonerosive acid-damaged esophageal epithelium. Am J Gastroenterol. 2004;99(1):13–22. CrossRef
- Farre R, et al. Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces. Gut. 2008;57(10):1366–74. CrossRef
- Farre R, et al. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus. Gut. 2010;59(2):164–9. CrossRef
- Jovov B, et al. Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol. 2011;106(6):1039–47. CrossRef
- Lundin P, et al. Bioimpedance spectroscopy: a new tool to assess early esophageal changes linked to gastroesophageal reflux disease? Dis Esophagus. 2011;24(7):462–9. CrossRef
- Orlando LA, Orlando RC. Dilated intercellular spaces as a marker of GERD. Curr Gastroenterol Rep. 2009;11(3):190–4. CrossRef
- van Malenstein H, Farre R, Sifrim D. Esophageal dilated intercellular spaces (DIS) and nonerosive reflux disease. 2008;103(4):1021–28.
- Farre R, et al. Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces. Gut. 2007;56(9):1191–7. CrossRef
- Colegio OR, et al. Claudins create charge-selective channels in the paracellular pathway between epithelial cells. Am J Physiol Cell Physiol. 2002;283(1):C142–7. CrossRef
- Chen X, et al. Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins. Am J Physiol Gastrointest Liver Physiol. 2011;301(2):G203–9. CrossRef
- Oshima T, et al. Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers. Lab Invest. 2011;92(1):22–31. CrossRef
- Asaoka D, et al. Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis. J Gastroenterol. 2005;40(8):781–90. CrossRef
- Oguro M, et al. Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease. J Gastroenterol. 2011;46(5):629–38. CrossRef
- Jones R, et al. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009;30(10):1030–8. CrossRef
- Vakil N, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–20 (quiz 1943).
- Savarino E, et al. Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease. Gut. 2009;58(9):1185–91. CrossRef
- Savarino E, et al. Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy. Am J Gastroenterol. 2010;105(5):1053–61. CrossRef
- Zerbib F, et al. Normal values and day-to-day variability of 24-h ambulatory oesophageal impedance-pH monitoring in a Belgian-French cohort of healthy subjects. Aliment Pharmacol Ther. 2005;22(10):1011–21. CrossRef
- Cui R, et al. The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower-esophagus of GERD patients. Dis Esophagus. 2011;24(1):1–5. CrossRef
- Ribolsi M, et al. Intercellular space diameters of the oesophageal epithelium in NERD patients: head to head comparison between light and electron microscopy analysis. Dig Liver Dis. 2009;41(1):9–14. CrossRef
- Xavier LL, et al. A simple and fast densitometric method for the analysis of tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and in the ventral tegmental area. Brain Res Brain Res Protoc. 2005;16(1–3):58–64. CrossRef
- Wang CJ, et al. Survivin expression quantified by Image Pro-Plus compared with visual assessment. Appl Immunohistochem Mol Morphol. 2009;17(6):530–5. CrossRef
- Richter JE. Role of the gastric refluxate in gastroesophageal reflux disease: acid, weak acid and bile. Am J Med Sci. 2009;338(2):89–95. CrossRef
- Wang K, et al. Diagnostic values of GerdQ, 24-h ambulatory oesophageal pH and impedance-pH monitoring in Barrett’s esophagus, reflux esophagitis and non-erosive reflux disease. Zhonghua Yi Xue Za Zhi. 2011;91(18):1228–32.
- Lacy BE, Chehade R, Crowell MD. A prospective study to compare a symptom-based reflux disease questionnaire to 48-h wireless ph monitoring for the identification of gastroesophageal reflux (revised 2-26-11). Am J Gastroenterol. 2011;106(9):1604–11. CrossRef
- Calabrese C, et al. Reversibility of GERD ultrastructural alterations and relief of symptoms after omeprazole treatment. Am J Gastroenterol. 2005;100(3):537–42. CrossRef
- Calabrese C, et al. Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux. World J Gastroenterol. 2005;11(12):1876–80.
- Xue Y, Zhou LY, Lin SR. Dilated intercellular spaces in gastroesophageal reflux disease patients and the changes of intercellular spaces after omeprazole treatment. Chin Med J (Engl). 2008;121(14):1297–301.
- Tobey NA, et al. Physicochemical basis for dilated intercellular spaces in non-erosive acid-damaged rabbit esophageal epithelium. Dis Esophagus. 2008;21(8):757–64. CrossRef
- Orlando RC, et al. Esophageal disease: updated information on inflammation. Ann N Y Acad Sci. 2011;1232:369–75. CrossRef
- Krug SM, Fromm M, Gunzel D. Two-path impedance spectroscopy for measuring paracellular and transcellular epithelial resistance. Biophys J. 2009;97(8):2202–11. CrossRef
- Van Itallie C, Rahner C, Anderson JM. Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest. 2001;107(10):1319–27. CrossRef
- Tamura A, et al. Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine. Gastroenterology. 2011;140(3):913–23. CrossRef
- Harnett KM, et al. Viewpoints on acid-induced inflammatory mediators in esophageal mucosa. J Neurogastroenterol Motil. 2010;16(4):374–88. CrossRef
- Souza RF, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009;137(5):1776–84. CrossRef
- Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease
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Journal of Gastroenterology
Volume 48, Issue 5 , pp 601-610
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- Springer Japan
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- Baseline impedance
- Acid reflux
- Intercellular spaces
- Tight junction
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