Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 5009-5016
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.5009
Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients
Yasuhiro Tamura, Yasushi Funaki, Shinya Izawa, Akihito Iida, Yoshiharu Yamaguchi, Kazunori Adachi, Naotaka Ogasawara, Makoto Sasaki, Hiroshi Kaneko, Kunio Kasugai
Yasuhiro Tamura, Yasushi Funaki, Shinya Izawa, Akihito Iida, Yoshiharu Yamaguchi, Kazunori Adachi, Naotaka Ogasawara, Makoto Sasaki, Kunio Kasugai, Department of Gastroenterology, Division of Internal Medicine, Aichi Medical University School of Medicine, Aichi 480-1195, Japan
Yasushi Funaki, Department of Clinical Laboratory, Aichi Medical University School of Medicine, Aichi 480-1195, Japan
Hiroshi Kaneko, Department of Internal Medicine, Hoshigaoka Maternity Hospital, Aichi 480-1195, Japan
Author contributions: Tamura Y, Izawa S, Funaki Y and Kasugai K designed the research; Tamura Y, Yamaguchi Y, Adachi K and Iida A performed the experiments; Kaneko H and Sasaki M analyzed the data; and Ogasawara N, Tamura Y and Kasugai K wrote the paper.
Ethics approval: The study was reviewed and approved by the Aichi Medical University School of Medicine.
Clinical trial registration: This study is not registered at Uniform Resource Locator of World Wide Web.
Informed consent: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest: Kunio Kasugai received research grants from the Research Organization for Daiich Sankyo Co., Ltd., Astra Zeneca Co., Ltd., and Takeda Pharmaceutical CO., Ltd. The other authors have no conflicts of interest to declare.
Data sharing: No additional data is available.
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: Yasushi Funaki, MD, Department of Gastroenterology, Division of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan. momomaru@aichi-med-u.ac.jp
Telephone: +81-561-623311 Fax: +81-561-621508
Received: October 2, 2014
Peer-review started: October 3, 2014
First decision: November 14, 2014
Revised: November 21, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 28, 2015
Processing time: 207 Days and 0 Hours
Abstract

AIM: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients.

METHODS: A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria.

RESULTS: Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences.

CONCLUSION: Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.

Keywords: Functional heartburn; Endoscopy-negative reflux disease; Proton pump inhibitor-resistant; Rome III criteria; 24-h multichannel intraluminal impedance-pH testing

Core tip: The Rome III criteria define functional heartburn (FH) by normal esophageal acid exposure time, with no relationship between symptoms and reflux, and no response to proton pump inhibitor (PPI) treatment. However, in Japanese clinical practice, PPI-refractory non-erosive reflux disease is often treated as FH, thought the pathophysiology of these diseases is not clear. In this study, we found no differences in the clinical characteristics of FH and PPI-refractory endoscopy-negative reflux disease, and recommend using manometry and 24-h multichannel intraluminal impedance-pH testing to differentiate between these two conditions.