Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH-impedance studies performed on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from ‘on PPI’ pH-impedance studies predicting need for escalation of therapy.
De-identified pH-impedance studies performed on BID PPI (Diversatek, Boulder, CO) in healthy volunteers (n=66, median 37.5 yr, 43.9% female), and patients with proven GERD (European heartburn-predominant cohort: n=43, median age 57.0 yr, 55.8% female; North American regurgitation-predominant cohort: n=42, median age 41.6 yr, 42.9% female) were analyzed. Median values and interquartile ranges (IQR) for pH-impedance metrics in healthy volunteers were compared to proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response.
Both conventional and novel reflux metrics were similar between PPI responders and non-responders (p≥0.1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET>4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, 57.1% and 82.4% of whom reported non-response; 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted non-response (sensitivity 0.62, specificity 0.51, p=0.22), while 40 reflux episodes had better performance characteristics (sensitivity 0.80, specificity 0.51, p=0.002); 79% with these metrics improved with invasive GERD management.
Combinations of abnormal ‘on PPI’ pH-impedance metrics are associated with PPI non-response in proven GERD patients, and can be targeted for treatment escalation including surgery, particularly in regurgitation predominant GERD.

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