Nonerosive reflux disease (NERD) is a distinct pattern of gastroesophageal reflux disease (GERD). It is defined as a subcategory of GERD characterized by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions/breaks at conventional endoscopy. In clinical practice, patients with reflux symptoms and negative endoscopic findings are markedly heterogeneous. The potential explanations for the symptom generation in NERD include microscopic inflammation, visceral hypersensitivity (stress and sleep), and sustained esophageal contractions. The use of 24-hour esophageal impedance and pH monitoring gives further insight into reflux characteristics and symptom association relevant to NERD. The treatment choice of NERD still relies on acid-suppression therapy. Initially, patients can be treated by a proton pump inhibitor (PPI; standard dose, once daily) for 2–4 weeks. If initial treatment fails to elicit adequate symptom control, increasing the PPI dose (standard dose PPI twice daily) is recommended. In patients with poor response to appropriate PPI treatment, 24-hour esophageal impedance and pH monitoring is indicated to differentiate acid-reflux-related NERD, weakly acid-reflux-related NERD (hypersensitive esophagus), nonacid-reflux-related NERD, and functional heartburn. The response is less effective in NERD as compared with erosive esophagitis. 1. Definitions of Gastroesophageal Reflux Disease and Nonerosive Reflux Disease Gastroesophageal reflux disease (GERD) has been defined in the Montreal Consensus Report as a chronic condition that develops when the reflux of gastric contents into the esophagus in significant quantities causes troublesome symptoms with or without mucosal erosions and/or relevant complications [1]. The typical symptoms of GERD are recognized as heartburn and/or acid regurgitation. GERD is a common disorder with its prevalence, as defined by at least weekly heartburn and/or acid regurgitation, estimated to range from 10 to 20% in western countries and is less than 5% in Asian countries [2]. However, it has been demonstrated that GERD is emerging as a leading digestive disorder in Asian countries [3] and has an adverse impact on health-related quality of life [4]. It is noteworthy that symptoms and esophageal lesions do not necessarily exist together. A proportion of patients with erosive esophagitis have no symptoms, whereas 50–85% of patients with typical reflux symptoms have no endoscopic evidence of erosive esophagitis [5]. The latter group of GERD patients is considered to have nonerosive reflux disease (NERD)
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