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Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring
  1. I Mainie1,
  2. R Tutuian2,
  3. S Shay2,
  4. M Vela1,
  5. X Zhang3,
  6. D Sifrim3,
  7. D O Castell1
  1. 1Division of Gastroenterology and Hepatology, Medical University South Carolina, Charleston, South Carolina, USA
  2. 2Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3Centre of Gastroenterological Research, Catholic University of Leuven, Belgium
  1. Correspondence to:
    Dr I Mainie
    Medical University South Carolina, 96 Jonathan Lucas St, 210 Clinical Science Building, PO Box 250327 Charleston. SC 29425, USA; mainie{at}


Background and aims: Empiric proton pump inhibitor (PPI) trials have become increasingly popular leading to gastroenterologists frequently evaluating gastro-oesophageal reflux disease (GORD) patients only after they have “failed” PPI therapy. Combined multichannel intraluminal impedance and pH (MII-pH) monitoring has the ability to detect gastro-oesophageal reflux (GOR) episodes independent of their pH and evaluate the relationship between symptoms and all types of GOR. Using this technique, we aimed to characterise the frequency of acid and non-acid reflux (NAR) and their relationship to typical and atypical GOR symptoms in patients on PPI therapy.

Methods: Patients with persistent GORD symptoms referred to three centres underwent 24 hour combined MII-pH monitoring while taking PPIs at least twice daily. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15, and 17 cm above the lower oesophageal sphincter (LOS) and classified into acid or non-acid based on pH data from 5 cm above the LOS. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes.

Results: A total of 168 patients (103 (61%) females and 65 (39%) males; mean age 53 (range 18–85) years) underwent combined MII-pH monitoring while taking PPIs at least twice daily. One hundred and forty four (86%) patients recorded symptoms during the study day and 24 (15%) patients had no symptoms during testing. Sixty nine (48%) symptomatic patients had a positive SI for at least one symptom (16 (11%) with acid reflux and 53 (37%) with NAR) and 75 (52%) had a negative SI. A total of 171 (57%) typical GORD symptoms were recorded, 19 (11%) had a positive SI for acid reflux, 52 (31%) for NAR, and 100 (58%) had a negative SI. One hundred and thirty one (43%) atypical symptoms were recorded, four (3%) had a positive SI for acid reflux, 25 (19%) had a positive SI for NAR, and 102 (78%) had a negative SI.

Conclusion: Combined MII-pH identifies the relation of reflux of all types to persistent symptoms and the importance of NAR in patients taking PPIs.

  • MII-pH, multichannel intraluminal impedance and pH
  • LOS, lower oesophageal sphincter
  • TLOSR, transient lower oesophageal sphincter relaxation
  • GOR, gastro-oesophageal reflux
  • GORD, gastro-oesophageal reflux disease
  • PPI, proton pump inhibitor
  • SI, symptom index
  • SAP, symptom association probability
  • NAR, non-acid reflux
  • multichannel intraluminal impedance and pH
  • gastro-oesophageal reflux disease
  • non-acid reflux

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