Original ContributionsArea under pH 4: a more sensitive parameter for the quantitative analysis of esophageal acid exposure in adults

OBJECTIVE: Traditional quantitative analysis of 24-h esophageal pH monitoring data does not include the pH of reflux episodes. Area under pH 4 (AU4) is a recently introduced parameter that describes the acid exposure rate through both duration and depth of pH falls. METHODS: In Study A, we enrolled 20 healthy controls and 42 patients (18 without esophagitis, 24 with Savary I–III esophagitis) in a study evaluating reference values for 24-h reflux time at pH <4 (RT) and 24-h AU4 by means of receiver operating characteristic (ROC) discriminant analysis. For Study B, we next prospectively applied the resulting cutoffs to 16 healthy controls and to 110 gastroesophageal reflux (GERD) patients (55 with esophagitis) to adjust sensitivity, specificity, and predictive values of both RT and AU4. RESULTS: In Study A, the best cutoff values were 5.1% for RT (Area Index ± SE, 0.899 ± 0.038; 95% confidence interval [C.I.], 0.796 ± 0.961) and 36.1 pH × min for AU4 (Area Index ± SE, 0.935 ± 0.03; 95% C.I., 0.842 ± 0.981); AU4 gave the best performance (p = 0.038 vs RT) in discriminating controls and GERD patients. In Study B, RT was abnormal in three controls and 79 patients; AU4 identified all the controls and patients with abnormal RT and also 10/31 patients (32.3%) with so-called “normal” acid exposure (according to RT). In the whole GERD group of patients, AU4 and RT specificity was 81.2%, whereas sensitivity was 71.8% for RT and 80.9% for AU4 (χ2, 61.831; DF, 1; p < 0.005); PPV/NPV were 96.3%/29.5% for RT, and 96.7%/38.2% for AU4. CONCLUSIONS: AU4 appears to be a simple and sensitive quantitative parameter to measure the esophageal acid exposure in adults submitted to 24-h pH monitoring, and it could be an useful clinical aid in evaluating normal RT tests where, from a clinical point of view, a reflux disease is highly likely.