Predictors of proton pump inhibitor failure in non-erosive reflux disease: A study with impedance-pH monitoring and high-resolution manometry

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Approximately one-third of gastroesophageal reflux disease (GERD) patients have symptoms resistant to proton pump inhibitor (PPI). We used the high-resolution manometry (HRM) and multichannel intraluminal impedance-pH (MII-pH) monitoring to investigate potential predictors of PPI failure in non-erosive reflux disease (NERD) patients.


One hundred and seventeen NERD patients were included, within which there were 44 PPI failure patients. The symptomatic questionnaire GerdQ, HRM and 24-hour MII-pH monitoring were performed before PPI therapy. PPI failure was defined as persistent reflux symptoms for more than 1 day during the last week on esomeprazole (20 mg twice daily) for continuous 4 weeks. The predictors for PPI failure were investigated by multivariable logistic regression analysis.

Key Results

Proton pump inhibitor failure patients had lower body mass index (BMI) and more concomitant functional dyspepsia (FD) symptoms. PPI failure patients had a higher percentage of type I esophagogastric junction (EGJ) morphology (p = 0.005), increased EGJ augmentation (p = 0.000), higher prevalence of esophageal motility disorders (p = 0.005) and a higher ratio of negative symptom index (SI, p = 0.000). Multivariable regression analysis showed that concomitance of FD symptoms, EGJ augmentation and negative SI were independent risk factors for PPI failure in NERD.

Conclusions & Inferences

Approximately half of PPI failure patients were found to have esophageal motility disorders in HRM. The independent risk factors for PPI failure in NERD were concomitant FD symptoms, increased EGJ augmentation and negative SI.

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