The Role of Nonacid Reflux in NERD
The Role of Nonacid Reflux in NERD
Introduction: 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.
Aim: 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 ≥ 50%), and symptom association probability (SAP; positive if ≥ 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%).
Conclusion: 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.
Gastroesophageal reflux disease (GERD) is one of the most common chronic gastrointestinal diseases in western countries. For many years, GERD was diagnosed by the presence of esophageal erosions. Recent studies documented that up to 70% of reflux patients have typical reflux symptoms (i.e., heartburn and/or regurgitation) in the absence of endoscopically visible esophageal mucosal injuries, making nonerosive reflux disease (NERD) the more common form of reflux disease. According to Fass et al., when including esophageal symptom association into the definition, NERD patients can be further subclassified into three distinct groups: (a) patients with an abnormal acid exposure time (AET), (b) patients with normal AET and positive symptom association ("sensitive esophagus"), and (c) patients with typical reflux symptoms, normal endoscopy, normal distal esophageal acid exposure, and negative symptom association ("functional heartburn"). This subclassification is clinically important as patients of the first group respond better to acid-suppressive therapy, while those with functional heartburn have a poorer response to acid-suppressive therapy and are more likely to have an accompanying psychopathology. While there are no precise data on the prevalence of these subforms of NERD, the estimates suggest that approximately 40% of patients with reflux symptoms and normal endoscopy have functional heartburn.
Recognizing that stimuli other than acid can evoke typical reflux symptoms, limiting reflux testing to ambulatory pH monitoring may lead to an overestimation of patients with functional heartburn. In recent years, new technologies have evolved complementing esophageal pH monitoring and allowing detection of gastroesophageal reflux independent of the acid content. In particular, the combination of conventional pH monitoring with esophageal intraluminal electrical impedance monitoring offers the opportunity to detect gastroesophageal reflux episodes based on the changes in electrical conductivity within the esophagus, allowing a more comprehensive characterization of reflux episodes based on physical (i.e., liquid, gas, or mixed) and chemical (i.e., acid and nonacid) properties of the refluxate. So far, the utility of combined impedance-pH monitoring to characterize gastroesophageal reflux episodes in NERD patients has been underinvestigated.
The aim of the present study was to assess the prevalence of acid and nonacid reflux episodes and their association with typical symptoms in NERD patients. An additional aim was to evaluate the impact of identifying reflux episodes missed by conventional pH monitoring (i.e., nonacid reflux episodes) on diagnosing patients with functional heartburn from the rest of the NERD population.
Introduction: 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.
Aim: 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 ≥ 50%), and symptom association probability (SAP; positive if ≥ 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%).
Conclusion: 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.
Gastroesophageal reflux disease (GERD) is one of the most common chronic gastrointestinal diseases in western countries. For many years, GERD was diagnosed by the presence of esophageal erosions. Recent studies documented that up to 70% of reflux patients have typical reflux symptoms (i.e., heartburn and/or regurgitation) in the absence of endoscopically visible esophageal mucosal injuries, making nonerosive reflux disease (NERD) the more common form of reflux disease. According to Fass et al., when including esophageal symptom association into the definition, NERD patients can be further subclassified into three distinct groups: (a) patients with an abnormal acid exposure time (AET), (b) patients with normal AET and positive symptom association ("sensitive esophagus"), and (c) patients with typical reflux symptoms, normal endoscopy, normal distal esophageal acid exposure, and negative symptom association ("functional heartburn"). This subclassification is clinically important as patients of the first group respond better to acid-suppressive therapy, while those with functional heartburn have a poorer response to acid-suppressive therapy and are more likely to have an accompanying psychopathology. While there are no precise data on the prevalence of these subforms of NERD, the estimates suggest that approximately 40% of patients with reflux symptoms and normal endoscopy have functional heartburn.
Recognizing that stimuli other than acid can evoke typical reflux symptoms, limiting reflux testing to ambulatory pH monitoring may lead to an overestimation of patients with functional heartburn. In recent years, new technologies have evolved complementing esophageal pH monitoring and allowing detection of gastroesophageal reflux independent of the acid content. In particular, the combination of conventional pH monitoring with esophageal intraluminal electrical impedance monitoring offers the opportunity to detect gastroesophageal reflux episodes based on the changes in electrical conductivity within the esophagus, allowing a more comprehensive characterization of reflux episodes based on physical (i.e., liquid, gas, or mixed) and chemical (i.e., acid and nonacid) properties of the refluxate. So far, the utility of combined impedance-pH monitoring to characterize gastroesophageal reflux episodes in NERD patients has been underinvestigated.
The aim of the present study was to assess the prevalence of acid and nonacid reflux episodes and their association with typical symptoms in NERD patients. An additional aim was to evaluate the impact of identifying reflux episodes missed by conventional pH monitoring (i.e., nonacid reflux episodes) on diagnosing patients with functional heartburn from the rest of the NERD population.
