Tu1883 Esophageal Epithelial-Derived IL-33 Acts As an Exaggerator of Inflammation in the Pathogenesis of GERD

Abstract

BACKGROUND: Intraluminal impedance baseline (IB) levels are determined by the conductivity of the esophageal wall and have been shown to be decreased in gastro-esophageal reflux disease (GERD) patients. It has been proposed that IB values may be used as a marker of reflux-induced changes in esophageal mucosal integrity (Farre et al. 2011), although there is no complete agreement on the most appropriate time period to assess IB (upright or recumbent). Altered esophageal mucosal integrity has been proposed as one of the pathological mechanisms associated with persisting symptom perception in GERD patients. Nevertheless, possible alterations in mucosal integrity in refractory GERD patients have not been assessed. The aims of the present study were: 1) to test whether IB measurements differ between the upright and recumbent period in healthy volunteers (HV) and refractory GERD patients on PPI and 2) to evaluate whether mucosal integrity is impaired in refractory GERD patients. METHOD: Ambulatory 24-h pH-impedance tracings from 16 refractory GERD patients (46±4 years, 7 male) as well as 20 HV (49±3 years, 11 male) both on proton pump inhibitor (PPI) therapy (40 mg) were retrospectively analyzed. Mean IB levels in the distal at 3 and 5 cm and in the proximal esophagus at 15 cm were assessed in two stable periods of 30 seconds in a time window of 30 minutes (excluding swallows and reflux events), both in the upright and recumbent positions. Values were expressed as mean±SEM. RESULTS: Both in HV and refractory GERD patients on PPI therapy, mean baseline values at 3 and 5 cm were comparable in upright and recumbent position. Moreover, at 15 cm, IB values were significantly lower in the recumbent period only in HV. In the upright position, IB at 3, 5 and 15 cm was significantly lower in GERD patients compared to HV on PPI. In contrast, in the recumbent position there were no significant differences in IB values between GERD patients and HV. Nevertheless, there was a tendency for IB to be lower in patients both at 3 (p=0.06) as well as at 15 cm (p=0.06). CONCLUSIONS: Refractory GERD patients on PPI have an impaired mucosal integrity in the distal and proximal esophagus. IB measurements in the upright period seem superior to evaluate alterations in mucosal integrity in GERD patients and to distinguish them from health.