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World J Gastroenterol. 2015 Apr 28;21(16):5009-16. doi: 10.3748/wjg.v21.i16.5009.

Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

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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.



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


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.


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.


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.


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

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