Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment

Abstract

Background/aims: Esophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment.

Methods: Ninety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients.

Results: The intercellular spaces were dilated in both EE and NERD patients (P < 0.05). The value 0.73 µm could be used as the cut-off DIS value to distinguish patients from controls (area under the curve [AUC] = 0.849, P < 0.01). One thousand seven hundred sixty-four ohms could be used as the cut-off impedance values to distinguish patients from controls (AUC = 0.794, P < 0.01). The baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time (r = -0.527, P < 0.05). There was a weak correlation between DIS and baseline impedance (r = -0.230, P < 0.05). "Baseline impedance > 1764 Ω" was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P < 0.01).

Conclusions: The DIS and decreased baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment.

Keywords: Impedance; Intercellular spaces; Proton pump inhibitor.

Figure 1

The measurement of dilated intercellular spaces. Ten randomly selected perpendicular trans-sections to adjacent cell membranes were measured on the chosen cell which had clear demarcation with surrounding 5–6 cells. BL, basal length.

Figure 2

The calculation of baseline impedance. The impedance values were assessed on the site above lower esophageal sphincter (LES) 5 cm and in the first stable 60-second times in every hour during the night when the individuals take supine position. Then the average values were taken as the mean nocturnal baseline impedance.

Figure 3

The comparison of intercellular space diameter (ISD) and mean nocturnal baseline impedance among 3 subgroups and controls. The ISD of patients were larger than that of healthy controls, whether with or without esophagitis (P < 0.05). The baseline impedance in erosive esophagitis (EE) and non-erosive reflux disease (NERD) patients was lower than that in patients with hypersensitive esophagus (HE) and healthy controls (P < 0.05).

Figure 4

The receiver operating characteristic (ROC) curve of intercellular space diameter (ISD) and Impedance. AUC, area under the curve.

Figure 5

The baseline impedance correlated to acid exposure time (AET)% and dilated intercellular spaces (DIS) in the patients. The impedance correlated to the AET% negatively (r = −0.527, P < 0.01), and there was also a negative weak linear correlation between baseline impedance and DIS (r = −0.230, P < 0.05).