Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease M. CICALA*, S. EMERENZIANI*, R. CAVIGLIA*, M. P. L. GUARINO*, P. VAVASSORI  , M. RIBOLSI*, S. CAROTTI*, T. PETITTI à & F. PALLONE   *Department of Digestive Disease, University Campus Bio Medico, Rome, Italy;  Department of Internal Medicine, University Tor Vergata, Rome, Italy; àDepartment of Epidemiology, University Campus Bio Medico, Rome, Italy Accepted for publication 25 June 2003 SUMMARY Background: The majority of patients with gastro- oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non-erosive gastro-oesophageal reflux disease are less responsive than patients with oesopha- gitis to acid-suppressive therapy. Aim: To assess the role of acid reflux in gastro- oesophageal reflux disease symptoms. Methods: The spatio-temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non-erosive gastro-oesophageal reflux disease and 20 patients with erosive oesopha- gitis. Results: Compared with healthy controls, all patients showed a higher intra-oesophageal proximal spread of acid, which was prominent in patients with non-erosive gastro-oesophageal reflux disease (> 50% of events lasting for 1–2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confid- ence interval, 4.6–12.5), being maximal in patients with non-erosive gastro-oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2–22.3). Conclusions: Patients with non-erosive gastro-oeso- phageal reflux disease are characterized by a signifi- cantly higher proportion of proximal acid refluxes and a higher sensitivity to short-lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non-erosive gastro- oesophageal reflux disease presenting with a normal pH-metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid-suppressive treatment. INTRODUCTION Pathophysiological studies have provided substantial data on the mechanisms responsible for the oesophageal reflux of gastric contents in both physiological and pathological conditions. 1–5 The presence of gastro- oesophageal reflux disease (GERD) is currently defined on the basis of typical symptoms and/or their impact on the health-related quality of life. 6 However, the main determinants of GERD symptoms still remain to be fully elucidated. Studies using intraluminal impedance mon- itoring in combination with pH and bile monitoring have confirmed that, of the gastric contents, acid reflux plays a major role in eliciting symptoms and, at the same time, is related to disease complications. 7–9 Patients with GERD not exhibiting oesophageal mucosal injury at endoscopy, namely patients with non-erosive gastro-oesophageal reflux disease (NERD), account for Correspondence to: Dr M. Cicala, Department of Digestive Disease, Uni- versity Campus Bio Medico, Rome, Italy. E-mail: m.cicala@unicampus.it Aliment Pharmacol Ther 2003; 18: 605–613. doi: 10.1046/j.1365-2036.2003.01702.x Ó 2003 Blackwell Publishing Ltd 605