Total Integrated Acidity Exposure Predicts PPI Response in Nonerosive Reflux Disease

Up to 40% of patients with gastroesophageal reflux disease (GERD) report incomplete or absent symptomatic response to proton pump inhibitor (PPI) therapy. Despite this gap, acid exposure time (AET) remains the reference metric for defining pathologic reflux. AET is a time-based measure that treats all periods of pH <4 as biologically equivalent, even though hydrogen ion concentration rises exponentially as pH falls. These researchers aimed to determine whether total integrated acidity exposure (TIAE) better predicts PPI response than conventional AET in patients with nonerosive or mild reflux disease.

This retrospective analysis prospectively collected impedance-pH data from adults with dominant esophageal GERD symptoms who underwent monitoring while off acid-suppressive therapy, after at least a 7-day washout, and following high-resolution manometry. The researchers excluded patients with esophageal motility disorders, hiatal hernia >2 cm, LA grade B-D erosive esophagitis, or extraesophageal-predominant symptoms.

The authors calculated TIAE by exporting raw pH values at 1-second resolution, converting each to hydrogen ion concentration, and summing this value over time for reflux episodes with pH <4. They then further stratified the pH findings into ranges (≤2, >2 to ≤3, and >3 to ≤4) and compared these data with TIAE for full pH <7.

Among the 174 eligible patients, including 97 PPI responders and 77 nonresponders, responders showed significantly higher TIAE than nonresponders and controls. TIAE outperformed AET for discriminating PPI response (receiver operating characteristic area under the curve, 0.78 vs 0.64) and remained independently associated with response in multivariable analysis (odds ratio, 1.18 per unit increase; 95% confidence interval, 1.07-1.30). In the clinically inconclusive AET range between 4% and 7%, TIAE correctly classified most responders and nonresponders.