Pathogenesis of proton-pump inhibitor-refractory non-erosive reflux disease according to multichannel intraluminal impedance-pH monitoring

Background and Aim: Proton-pump inhibitor (PPI) therapy is the first-line treatment for gastroesophageal reflux disease; however, there are some reports of PPI failure in cases of non-erosive reflux disease (NERD). Among the pathogenic factors associated with PPI-refractory NERD, reflux other than acid reflux can not be detected by conventional pH monitoring. The purpose of this study was to clarify the usefulness of multichannel intraluminal impedance-pH (MII-pH) monitoring for PPI-refractory NERD patients and examine the pathogenesis. Methods: We used MII-pH monitoring to examine 29 PPI-refractory NERD patients on PPI treatment. Reflux parameters, symptom index (SI: positive if ≥50%), and proximal migration were analyzed. The acidity of the reflux was divided into acid (nadir pH≤4) and non-acid (nadir pH>4). Subjects were classified into reflux-related disease (abnormal reflux parameters or positive SI) and non-reflux-related disease (normal reflux parameters and negative SI). Results: Of the 29 subjects, 21 were diagnosed with reflux-related disease, including 6 with acid reflux type and 15 with non-acid reflux type, and 8 were diagnosed with non-reflux-related disease. Of the total 1816 liquid reflux episodes, 834 showed proximal migration, which was more common in symptomatic reflux than in asymptomatic reflux. Conclusions: MII-pH monitoring could distinguish reflux-related disease (especially non-acid type) from PPI-refractory NERD. Proximal migration was associated with symptomatic reflux in PPI-refractory NERD patients.