The role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy

Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. While the role of acid reflux has been established, the relevance of nonacid reflux in generating symptoms in NERD is unknown.To evaluate the diagnostic utility of impedance-pH monitoring in NERD patients.Patients with typical reflux symptoms (heartburn and/or regurgitation) and normal endoscopy (NERD) underwent a combined impedance-pH monitoring off proton pump inhibitor (PPI) therapy. Previously investigated 48 healthy volunteers served as controls. Distal esophageal acid exposure (% time pH4), number of acid and nonacid reflux episodes, 2-min window symptom index (SI; positive ifor = 50%), and symptom association probability (SAP; positive ifor = 95%) were calculated.Between June 2004 and June 2007, 150 NERD patients (82 women, mean age 48 yr, range 18-78 yr) reported symptoms during the impedance-pH monitoring. NERD patients had more reflux episodes (median [25th-75th percentile]) compared with healthy volunteers (total: 46 [26-65] vs 32 [18-43], P0.05; acid: 29 [14-43] vs 17 [8.5-31.0], P0.05; and nonacid: 20 [15-27] vs 18 [13.5-26.0], P = NS). Sixty-three (42%) patients had abnormal % time pH4. Among 87 patients with normal % time pH4., 22 (15%) had a positive SAP for acid, 19 (12%) for nonacid reflux, and 7 (5%) for both. Classifying patients with symptomatic nonacid reflux as having a hypersensitive esophagus reduced the number of patients with functional heartburn from 65 (43%) to 39 (26%).Monitoring for nonacid reflux in NERD patients reduces the proportion of patients classified as having "functional heartburn." Studies assessing the clinical implications of these findings are warranted.