1. Determinants of gastro-oesophageal reflux perception in patients with persistent symptoms despite proton pump inhibitors F Zerbib, A Duriez, S Roman, M Capdepont, F Mion R3 임효석 Gut 2008;57:156–160

2. Background Approximately 30-40% of patients have persistent symptoms of gastro-oesophageal reflux despite proton pump inhibitor (PPI) therapy. Acid component of the refluxate : : a major role in the pathophysiology of gastro-oesophageal reflux disease (GORD) Ambulatory pH monitoring : temporal relationship between symptoms and reflux episodes.

3. Aim To assess the factors associated with the perception of gastro- oesophageal reflux episodes detected by means of ambulatory 24 h oesophageal pH–impedance monitoring. (On PPI)

4. Methods Patients 59 patients : : pH–impedance study because of persistent typical GORD (Regurgitation, heartburn) symptoms despite adequate PPI therapy. 39 patients were excluded : : negative symptom–reflux association (n=35) no symptom occurrence during the 24 h recording (n=4) 20 patients (14 women, mean age 44.6 years, range 18–77) with typical GORD symptoms were finally included in the study.

5. 20 patients previously documented GORD by 1 ) endoscopy and/or pH study 2 ) persistent symptoms on PPI prescribed empirically for at least 2 weeks before the pH–impedance study. PPI prescribed (double dose) : twice-daily omeprazole 20 mg, lansoprazole 30 mg, rabeprazole 20 mg, pantoprazole 40 mg or esomeprazole 40 mg.

6. Study protocol - outpatients - outpatients - record pH at 5 cm and impedance at 3, 5, 7, 9, 15 and 17 cm - record pH at 5 cm and impedance at 3, 5, 7, 9, 15 and 17 cm proximal to the LOS. proximal to the LOS. Definitions of reflux episodes - Liquid reflux : retrograde 50% drop in impedance - Gas reflux : a rapid (3 kΩ/s) increase in impedance.5000 Ω occurring simultaneously at least in two oesophageal measuring segments,

7. GI Motility online (May 2006) | doi:10.1038/gimo31 Combined multichannel intraluminal impedance and pH catheter.

8. pHmetry (1) Acid reflux: oesophageal pH <4 (2) Weakly acidic reflux : oesophageal pH between 4 and 7 (3) Weakly alkaline reflux : reflux episodes during which nadir oesophageal pH does not drop below 7. Gastro-oesophageal reflux variables - upright and supine & symptomatic or not - composition (liquid or mixed liquid–gas) - chemical composition (acid, weakly acidic or weakly alkaline) - proximal reflux (reflux reaching the 15 cm impedance site) - median reflux bolus clearance time (determined 5 cm above the LOS) - bolus burden (cumulative oesophageal exposure to the bolus 1 h before the onset of the reflux episode) - number of preceding (1 h) acid and weakly acidic reflux episodes - acid clearance time, acid burden, nadir pH

9. Results Among the 20 patients included in this study, 6 reported regurgitation, 2 reported heartburn and 12 reported both symptoms. Endoscopy was normal in 14 patients, 2 - hiatal hernia without oesophagitis 1 - 1 - low grade oesophagitis 3 - short segment Barrett’s oesophagus

10. Table 1. Characteristics of symptomatic and asymptomatic reflux episodes in 20 patients with persisting symptoms on proton pump inhibitors High proximal extent : reflux reaching the 15 cm impedance site above the LOS (312)(961)

11. Figure 1. Rates of symptomatic and asymptomatic reflux events with high proximal extent in 20 patients with persisting symptoms on twice daily PPIs. Each white circle represents the percentage of reflux events with high proximal extent in an individual patient. The filled circles and associated lines are the median values for each group.

12. Table 2. Characteristics of 312 symptomatic reflux episodes in the supine and upright position in 20 patients with persisting symptoms on proton pump inhibitors

13. Table 3. Characteristics of reflux episodes associated with heartburn and regurgitation

14. Discussion Weakly acidic reflux episodes play a major role in eliciting symptoms in 30–40% of patients on PPI therapy.  double-dose PPIs High High proximal extent of the refluxate was the only factor associated with symptom perception. In patients off therapy, Bredenoord et al reported that not only higher proximal extent but also a larger pH drop, lower nadir pH and longer volume and acid clearance were associated with reflux perception.

15. In this study, the role of chemical composition of the refluxate may not be so relevant in patients with adequate acid-suppressive therapy. Reflux episodes eliciting heartburn were more frequently pure liquid and acidic, had a lower nadir pH and were more frequently associated with preceding acid reflux episodes.   the perception of heartburn is more sensitive to the chemical composition of the refluxate than regurgitation.

16. Conclusion The major role of proximal spread of reflux episodes as a determinant of perception in patients on PPI therapy. Compared with regurgitation, the chemical composition of the refluxate appears to be involved in the perception of heartburn. In patients with ‘‘refractory GORD’’, second intention antireflux therapies (eg, surgery, endoscopic procedures or drugs) should aim at not only reducing the number of reflux episodes but also limiting their proximal extent within the oesophagus.