The Role of Gastroesophageal Reflux in Relation to Symptom Onset in Patients with Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease Accompanied by an Underlying Esophageal Motor Disorder

Abstract

Background: The symptom improvement rate is low with proton pump inhibitors (PPIs) in nonerosive reflux disease (NERD). The underlying pathogenic mechanism is complex. Esophageal motility disorders (EMDs) are thought to be a factor, but their prevalence, type, symptoms and the role played by gastroesophageal reflux (GER) in symptom onset have not been fully investigated. Aim: To investigate the role of GER in symptom onset in PPI-refractory NERD patients with EMDs. Methods: This study comprised 76 patients withPPI-refractory NERD. Manometry was performed during PPI treatment and patients were divided into an EMD group and normal motility (non-EMD) group. Then, multichannel intraluminal impedance-pH monitoring was performed and medical interviews were conducted. Results: Nineteen patients (25%) had an EMD. Data were compared between 17 patients, excluding 2 with achalasia and 57 non-EMD patients. No significant differences were observed between groups in 24-hour intraesophageal pH <4 holding time (HT), mean number of GER episodes or mean number of proximal reflux episodes. The reflux-related symptom index (≥50%) showed a relationship between reflux and symptoms in 70.5% of EMD patients and 75% of non-EMD patients. In the EMD group, the score for FSSG (Frequency Scale for the Symptoms of GERD) question (Q)10 was significantly correlated with the number of GER episodes (r = 0.58, p = 0.02) and the number of proximal reflux episodes (r = 0.63, p = 0.02). In addition, the score for Q9 tended to be correlated with the number of GER episodes (r = 0.44, p = 0.06). Conclusion: Our results suggest that some PPI-refractory NERD patients have EMDs, and that GER plays a role in symptom onset.

Exploratory Research on Latent Esophageal Motility Disorders in Dysphagia Patients

“…Similar to the results reported by Izawa et al [7] who performed a procedure of HRM on patients with PPI-resistant NERD, this study had an incidence of esophageal motility disorder, with the difference not exceeding 25%. One possible reason is that Izawa et al [7] used the method of Castell and Castell [9] to evaluate esophageal motility function [8], but this may be an insufficient explanation.…”

“…One possible reason is that Izawa et al [7] used the method of Castell and Castell [9] to evaluate esophageal motility function [8], but this may be an insufficient explanation. Another difference between the studies is the chief complaint of patients: Izawa et al [7] used heartburn, which is the first item in the FSSG, whereas we used dysphagia, which is the ninth item in the FSSG. …”

The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

“…In a study of 76 patients with PPI refractory non-esophageal reflux disease, manometry was performed during PPI treatment, identifying 25% with an underlying esophageal motility disorder (Izawa et al ). 49 No significant differences were noted between the groups with esophageal motility disorder and non-esophageal motility disorder in their 24-h intraesophageal pH holding time, mean number of GER episodes, or mean number of proximal reflux episodes, suggesting that some PPI refractory NERD patients have underlying esophageal motility disorders. Conventional or high-resolution manometry should be performed in order to rule out severe motor disorders including EoE as mentioned above, achalasia, scleroderma, and other connective tissue diseases.…”

Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial

“…That is to say, results of the evaluation of the esophageal peristaltic motor function of patients with NERD implied that swallowed food may easily stagnate in the esophagus of patients with PPI-refractory NERD. Likewise, Izawa et al 20 reported that esophageal motility disorders, such as ineffective esophagus motility, nonspecific esophageal motility disorders, and hypertensive LES, were found in 25% of patients with PPI-refractory NERD.…”