Tu1874 A Low Mucosal Integrity in a Subgroup of Healthy Subjects Increases With Proton Pump Inhibitor Treatment

Abstract

Background: Esophageal epithelial integrity is considered an important factor in the prevention of tissue damage by gastric refluxate.We hypothesized that in patients with gastroesophageal reflux disease (GERD) the esophageal epithelial barrier function is impaired and less resistant in response to acid exposure. We therefore investigated esophageal epithelial integrity in GERD patients and in healthy controls both in the basal state and in response to acid exposure Methods: 14 patients with chronic GERD (8 with erosive esophagitis, 6 with non-erosive reflux disease) and 10 healthy controls (HC) were enrolled. Before endoscopy, GERD patients discontinued PPI therapy for 7 days. Six esophageal biopsies frommacroscopically normal mucosa were obtained approximately 5 cm above the gastroesophageal junction and directly transferred to a mini-Ussing chamber system. After an equilibration period, baseline TEER was assessed. Half of the biopsies were then exposed at their luminal side to an acidic solution (pH1) for 30 minutes. During exposure and after removal of the acidic solution, changes in TEER were analyzed relative to baseline TEER. Permeation to the paracellular permeation marker fluorescein (375 DA 1 mg/ml) was assessed in all biopsies (previous acid-exposed and non-exposed) for 120 minutes. Only subjects with at least two adequate biopsies (one for acid exposure, one as a control) were included. Results: Esophageal epithelium of GERD patients showed lower baseline TEER (127.7±13.3 Ω vs. 174.3±17.6 Ω, p=0.04) and a trend toward higher transmucosal permeation of fluorescein in the nonexposed biopsies when compared to healthy controls (serosal concentration (pmol/ml) after 120 min: 48.2 (7.6-66.7) vs. 6.8 (3.6-20.2), p=0.09 and AUC: 79.8 (12.9-135.6) vs. 9.0 (5.5-31.3), p=0.07). Acid exposure provoked a fall in TEER that was equal for the biopsies of GERD patients and healthy controls (-52.1±2.5% vs. -50.0±4.4% of baseline TEER). After removal of the acidic solution, TEER recovered also to a similar extent in GERD patients and healthy controls (89.6±3.8% vs. 93.8±3.0% of baseline TEER). However, maximum TEER was reached earlier in biopsies of GERD patients (54±9 min vs. 83±6 min (HC), p= 0.02) and at the end of the experiment, TEER relative to baseline was lower in biopsies of GERD patients (73.7±5.8% vs. 89.7±3.3% (HC) of baseline TEER, p<0.05). Conclusion: The esophageal epithelial barrier function of GERD patients is impaired, reflected by lower baseline transepithelial electrical resistance and a trend toward higher fluorescein permeation, and seems to be less resistant in response to acid exposure ex-vivo.