GERD consensus: The 15 year flight from Porto to Lyon

In November of 2002, 11 esophageal physiologists gathered in Porto to consolidate knowledge surrounding a new technology: intraluminal impedance monitoring. After decades of dependence on pH testing to define reflux, experts were wrestling with a growing body of evidence showing that not all reflux episodes, or symptoms, were associated with low pH.1,2 The resulting consensus laid out arguments for the use of acidic, weakly acidic, non-acidic, bilirubin-containing and mixed reflux as part of what was expected to become the new standard for esophageal physiologic testing, pH-impedance monitoring.3 Additionally, new advances in bilirubin monitoring had laid the groundwork for analysis of refluxate for bile. Presumed to play a role in mucosal injury and subsequent histopathology, bile also served as a marker for reflux of duodenal content into the esophagus.

Enthusiasm for the technology centered around impedance monitoring’s sensitivity — felt likely greater than 90% — in detecting flow and directionality of esophageal contents, independent of composition. By relying on the physical property that electrical flow is facilitated when fluid bridges two electrodes and hindered when air is present, impedance can provide extremely detailed information about intraluminal content.4 This was particularly compelling as a potential route for deciphering whether sensation correlated with reflux events not previously detectable.

By the time the field landed in Lyon in 2017, however, much had changed. Wireless pH monitoring had been introduced; it provided a simple endoscopic mechanism for streamlined work-up as well as an avenue for prolonged testing to overcome day-to-day variation in reflux patterns. Further, traditional manometry had fully given way to its higher resolution counterpart, which had already extended its reach beyond motility disorders into the evaluation of gastroesophageal reflux disease (GERD).5 Concurrently, an unforeseen conclusion was increasingly drawn: non-acidic reflux episodes alone did not predict response to GERD therapy, but pH drops did.6-8 This realization led to the Lyon consensus recommendation that testing be performed off proton pump inhibitor (PPI) for unproven GERD to better detect esophageal acid. Even in borderline cases, pH monitoring provided concrete data whereas impedance studies relied on the more subjective reflux-symptom association parameters. Therefore, impedance testing alone, on therapy, was considered insufficient to make a diagnosis of reflux disease. This was reflected in the Lyon document which favored acid exposure time (AET), given reproducibility, prediction of outcome and the potential for prolonged testing.9,10 These issues, coupled with the increasing ease of pH testing, brought impedance utility into question.

However, just as the pendulum swung away it has begun to swing back. On the back of recommendations from an international working group,11 impedance testing is now deemed necessary in those with persisting symptoms in the setting of previously confirmed GERD, in deciphering whether reflux associates with continuing symptoms while on acid suppressive therapy. The Lyon document thus incorporated prior GERD evidence into decision-making and choice of test, while also making room for utilization of novel impedance metrics, such as mean nocturnal baseline impedance (MNBI) and post reflux swallow induced peristaltic wave (PSPW), which had shown potential in predicting outcomes and so were also being used to differentiate indeterminate patients.12 Esophageal motor physiology and pathophysiology using HRM were also given a place in the adjudication of inconclusive reflux monitoring results.

Wireless pH monitoring had been introduced; it provided a simple endoscopic mechanism for streamlined work-up as well as an avenue for prolonged testing to overcome day-to-day variation in reflux patterns.

As the GERD community starts its ascent from Lyon, much is on the horizon. A novel approach to evaluating baseline impedance at endoscopy using a balloon mounted impedance electrode array can discriminate between reflux-induced changes in esophageal mucosal integrity, more severe inflammatory changes of eosinophilic esophagitis and normal mucosa. Evaluation of esophageal distensibility and contractility using the functional lumen imaging probe (FLIP), an offshoot of impedance based physics, can diagnose obstructive motility disorders masquerading as GERD during the same index endoscopy.

Now, as was the case in 2002, the proper approach must be realized on a case-by-case basis. A multi-pronged approach to investigation using old and new tools, while taking clinical presentation and management goals into consideration is preferable to the older ‘one size fits all’ approach. This allows for identification of any coexisting mechanical etiologies, diagnosis of motility diseases that could be confused for reflux, impaired contractility that could indicate difficulty clearing refluxate and correlation of symptoms with both physiological and pathological esophageal events.

Today’s esophageal physiologist has not just the benefit of knowledge provided by the Porto Consensus but also a plethora of additional testing modalities to delineate symptom etiology, as we learned in Lyon. The future of refractory symptom evaluation is likely to invoke the wisdom of the past: each patient must be considered as an individual and we must tailor our approach accordingly.

Dr. Rogers has no conflicts to disclose.

Dr. Gyawali consults and is on the speakers’ bureau for Medtronic and Diversatek. He also consults for Ironwood and Iso-thrive.
Dr. Gyawali is a member of the AGA Clinical Practice Updates Committee.

References

1. Wyman J.B., Dent J., Holloway R.H. Changes in oesophageal pH associated with gastro-oesophageal reflux. Are traditional criteria sensitive for detection of reflux? Scand J Gastroenterol. 1993;28:827-832.
2. Breumelhof R., Nadorp J.H., Akkermans LM, et al. Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain. Gastroenterol. 1990;99:1257-1264.
3. Sifrim D., Castell D., Dent J., et al. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004;53:1024-1031.
4. Sifrim D., Silny J., Holloway R.H., et al. Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance. Gut. 1999;44:47-54.
5. Gyawali C.P., Roman S., Bredenoord A.J., et al. Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group. Neurogastroenterol Motil. 2017;29.
6. Patel A., Sayuk G.S., Gyawali C.P. Prevalence, characteristics, and treatment outcomes of reflux hypersensitivity detected on pH-impedance monitoring. Neurogastroenterol Motil. 2016;28:1382-1390.
7. Roman S., Bruley des Varannes S., Pouderoux P., et al. Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic analysis for gastro-oesophageal reflux assessment. Neurogastroenterol Motil. 2006;18:978-986.
8. Bell R., Lipham J., Louie B., et al. Laparoscopic magnetic sphincter augmentation versus double-dose proton pump inhibitors for management of moderate-to-severe regurgitation in GERD: a randomized controlled trial. Gastrointest Endosc. 2019;89:14-22 e1.
9. Sweis R., Fox M., Anggiansah A., et al. Prolonged, wireless pH-studies have a high diagnostic yield in patients with reflux symptoms and negative 24-h catheter-based pH-studies. Neurogastroenterol Motil. 2011;23:419-426.
10. Prakash C., Clouse R.E. Value of extended recording time with wireless pH monitoring in evaluating gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2005;3:329-334.
11. Roman S., Gyawali C.P., Savarino E., et al. Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group. Neurogastroenterol Motil. 2017;29:1-15.
12. Martinucci I., de Bortoli N., Savarino E., et al. Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn. Neurogastroenterol Motil. 2014;26:546-555.

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