Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis

Abstract

Objectives: Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux (GER). It has been suggested that increased GER is due to low basal lower esophageal sphincter (LES) pressure and a high number of transient LES relaxations (TLESRs). The aim of our study was to reassess the mechanisms of GER in adult CF patients using state of the art upper-gastrointestinal physiology techniques: high-resolution manometry impedance (HRM-MII).

Methods: We studied 12 CF patients (age 32 range (19-58), 5 males/7 females) and 11 age-matched healthy volunteers (age 27 range (20-36), 4 males /7 females). HRM-MII was performed in a semi-recumbent position for 30 min during fasting and for 2 h after a standard meal (1,000 kcal). We measured total reflux and proximal extent of reflux with impedance; basal LES pressure, TLESRs, and gastroesophageal pressure gradient (GEPG) with HRM.

Results: Basal LES pressure was lower in CF patients compared with healthy controls, both in the pre- and postprandial period (preprandial 13 (7-22) vs. 24 (13-26) mm Hg, P = 0.04; postprandial 10 (8-14) vs. 18 (10-31) mm Hg, P = 0.01) and TLESRs were the main mechanism for reflux both in CF and in controls. We could not find a difference in the number of TLESRs in CF patients compared with healthy (14 (10-20) vs. 13 (10-24), P = not significant). However, reflux during TLESRs was more frequent in CF compared with healthy volunteers (80 (70-95) vs. 42 (20-78) %, P = 0.0058). GEPG during TLESRs was significantly higher in CF than in controls during inspiration (13.5 (9.5-15.8) vs. 7 (4-9.9) mm Hg, P = 0.004). This difference was due to a lower inspiratory intra-thoracic pressure in CF patients (-8.2 (-10.2-(-4.6) vs. -0.08 (-5.7-2.7) mm Hg, P = 0.002). Compared with controls, CF patients had significantly higher number of reflux episodes (13 (6-20) vs. 7 (3-9), P = 0.014) and CF patients also showed a higher proportion of reflux episodes with a high proximal extent compared with healthy volunteers (49 (22-50) vs. 0 (0-17) %, P = 0.0028).

Conclusions: CF patients have increased GER with a high proximal extent. Although we could not find a higher number of TLESRs in CF, there is a higher proportion of TLESRs associated with reflux. Unlike non-CF GER disease patients (with increased intra-abdominal pressure), reflux during TLESRs in CF is probably due to an increased GEPG mainly generated by a greater inspiratory negative intra-thoracic pressure.