When patients have persistent reflux symptoms while being treated with proton pump inhibitors (PPI), the key question is whether they have indeed PPI refractory reflux disease or another disorder explaining their symptoms. 24-hr pH-impedance monitoring can be used to either exclude or confirm reflux disease, this can be done while patient either continue or stop their PPIs in advance of the measurement. While there is consensus about what is a normal acid exposure off PPI, described in the Lyon Consensus as below the borderline range of 4-6% of total time, it is not clear when acid exposure is abnormal while being measured on PPI.
The authors of this study analysed pH impedance studies performed while on twice-daily PPI in healthy volunteers (n = 66), as well as in patients with proven gastroesophageal reflux disease (GERD) (n = 85). It showed reflux metrics were similar between PPI responders and nonresponders GERd patients despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (acid exposure time >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, an acid exposure time threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P = .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P = .002); 79% with these metrics improved with invasive GERD management.
These data show that combinations of abnormal pH impedance metrics on PPI are associated with PPI nonresponse in proven GERD patients, however, the predictive values seem to be too low to use in clinical practice. A hard cut-off to distinguish pH-impedance measurement values for patients and controls can therefore not be provided. It therefore seems preferable to measure patients with PPI refractory reflux symptoms after temporal cessation of PPI, as this allows a better distinction what is normal or not.
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