Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2015; 21(47): 13352-13359
Published online Dec 21, 2015. doi: 10.3748/wjg.v21.i47.13352
Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients
Kenichiro Nakagawa, Tomoyuki Koike, Katsunori Iijima, Masahiro Saito, Hiroki Kikuchi, Waku Hatta, Nobuyuki Ara, Kaname Uno, Naoki Asano, Tooru Shimosegawa
Kenichiro Nakagawa, Tomoyuki Koike, Katsunori Iijima, Masahiro Saito, Hiroki Kikuchi, Waku Hatta, Nobuyuki Ara, Kaname Uno, Naoki Asano, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai Miyagi 980-8574, Japan
Author contributions: Nakagawa K and Koike T performed the literature search and wrote the manuscript; Koike T and Iijima K participated in drafting the paper and performing critical revision for important intellectual content; Nakagawa K, Koike T and Iijima K performed the statistical analysis; Iijima K, Saito M, Kikuchi H, Hatta W, Ara N, Uno K, Asano N and Shimosegawa T interpreted the data; Shimosegawa T approved the final draft submitted.
Institutional review board statement: This study was approved by the Tohoku University Hospital Ethics Committee.
Informed consent statement: Informed consent was obtained from all subjects.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author at tkoike@rd5.so-net.ne.jp.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tomoyuki Koike, MD, PhD, Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi Aoba-ku, Sendai Miyagi 980-8574, Japan. tkoike@rd5.so-net.ne.jp
Telephone: +81-22-7177171 Fax: +81-22-7177177
Received: February 23, 2015
Peer-review started: February 24, 2015
First decision: March 26, 2015
Revised: April 13, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: December 21, 2015
Processing time: 295 Days and 5.4 Hours
Abstract

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients.

METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.

RESULTS: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS).

CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Keywords: Proton pump inhibitor; Symptomatic reflux episodes; Proximal reflux; Non-erosive reflux disease; Impedance-pH monitoring

Core tip: Thirty-five non-erosive reflux disease patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily, were included. In 14 (40%) symptom index (SI)-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (46.7%) than in distal ones (5.7%) (P < 0.001). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor of reflux perception in SI-positive patients on proton pump inhibitor (PPI).