title: The role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To evaluate the diagnostic utility of impedance-pH monitoring in NERD patients.
  
  
  METHODS
  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 pH < 4), number of acid and nonacid reflux episodes, 2-min window symptom index (SI; positive if > or = 50%), and symptom association probability (SAP; positive if > or = 95%) were calculated.
  
  
  RESULTS
  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], P < 0.05; acid: 29 [14-43] vs 17 [8.5-31.0], P < 0.05; and nonacid: 20 [15-27] vs 18 [13.5-26.0], P = NS). Sixty-three (42%) patients had abnormal % time pH < 4. Among 87 patients with normal % time pH < 4., 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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Di.M.I. Cattedra di Gastroenterologia, Università di Genova, Genova, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Savarino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zentilin
authors.forename: Radu
authors.initials: R
authors.lastname: Tutuian
authors.forename: Daniel
authors.initials: D
authors.lastname: Pohl
authors.forename: Domenico D
authors.initials: DD
authors.lastname: Casa
authors.forename: Marzio
authors.initials: M
authors.lastname: Frazzoni
authors.forename: Renzo
authors.initials: R
authors.lastname: Cestari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Savarino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016145:Endoscopy, Digestive System; D050782:Esophageal pH Monitoring; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult