Abstract
Heartburn is the most specific symptom of gastroesophageal reflux disease (GERD). In clinical practice, heartburn relief by a proton pump inhibitor (PPI) trial does suffice to confirm GERD. However, an objective diagnosis of GERD is required before anti-reflux endoscopic or surgical interventions, independently from PPI response. Thus, since normal findings at upper endoscopy are detected in the majority of patients with heartburn, reflux monitoring is often required. When traditional catheter-based or wireless pH tests are used, reflux episodes are conventionally identified by pH drops below 4.0 units. Combined impedance-pH monitoring has the advantage to provide a comprehensive assessment of both physical and chemical properties of refluxate and the distinction between acid and weakly acidic refluxes, both proven to cause heartburn. Unfortunately, the conventional impedance-pH parameters, namely acid exposure time and number of reflux events, are characterized by suboptimal diagnostic sensitivity, and the reliability of symptom–reflux association indexes remains questionable. Therefore, novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), have recently been proposed in order to achieve a better diagnostic yield. In fact, they proved to be highly accurate in distinguishing reflux-related from reflux-unrelated heartburn, off- as well as on-PPI therapy. Currently, manual review of impedance-pH tracings is needed because of the modest accuracy of available software tools for automated analysis. PSPW index and MNBI are highly applicable and reproducible, and their calculation requires a few additional minutes during the manual review of impedance-pH tracings. So far, we believe that PSPW index and MNBI are ready for prime time and should become part of the standard analysis of impedance-pH tracings for GERD diagnosis in patients with endoscopy-negative heartburn.
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Abbreviations
- AUC:
-
Area under the curve
- AET:
-
Acid exposure time
- ERD:
-
Erosive reflux disease
- FH:
-
Functional heartburn
- GERD:
-
Gastroesophageal reflux disease
- HE:
-
Hypersensitive esophagus
- MNBI:
-
Mean nocturnal baseline impedance
- NERD:
-
Non-erosive reflux disease
- PSPW:
-
Post-reflux swallow-induced peristaltic wave
- ROC:
-
Receiver operating characteristic
- SAP:
-
Symptom association probability
- SI:
-
Symptom index
References
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, and the Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–1920.
Kahrilas P, Shaheen N, Vaezi M. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology. 2008;135:1392–1413.
Katz P, Gerson L, Vela M. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308–328.
Savarino E, Zentilin P, Savarino V. NERD: an umbrella term including heterogeneous subpopulations. Nat Rev Gastroenterol Hepatol. 2013;10:371–380.
Galmiche JP, Clouse RE, Balint A, et al. Functional esophageal disorders. Gastroenterology. 2006;130:1459–1465.
Savarino E, De Bortoli N, Bellini M, et al. Practice guidelines on the use of esophageal manometry—a GISMAD-SIGE-AIGO medical position statement. Dig Liver Dis. 2016;48:1124–1135.
Kahrilas PJ, Quigley EMM. Clinical esophageal pH recording: a technical review for practice guideline development. Gastroenterology. 1996;110:1982–1996.
Hila A, Agrawal A, Castell DO. Combined multichannel intraluminal impedance and pH esophageal testing compared to pH alone for diagnosing both acid and weakly acidic gastroesophageal reflux. Clin Gastroenterol Hepatol. 2007;5:172–177.
Roberts NB. Review article: human pepsins—their multiplicity, function and role in reflux disease. Aliment Pharmacol Ther. 2006;24:2–9.
Pearson JP, Parikh S. Review article: nature and properties of gastro-oesophageal and extra-oesophageal refluxate. Aliment Pharmacol Ther. 2011;33:2–7.
Orlando RC. Review article: oesophageal tissue damage and protection. Aliment Pharmacol Ther. 2011;33:8–12.
Frazzoni M, Savarino E, Manno M, et al. Reflux patterns in patients with short segment Barrett’s oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy. Aliment Pharmacol Ther. 2009;30:508–515.
Frazzoni M, Conigliaro R, Melotti G. Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor-resistant reflux oesophagitis. Aliment Pharmacol Ther. 2011;33:601–606.
Hirano I, Richter JE and the Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines—esophageal reflux testing. Am J Gastroenterol. 2007; 102:668–685.
Gasiorowska A, Navarro-Rodriguez T, Wendel C, et al. Comparison of the degree of duodenogastroesophageal reflux and acid reflux between patients who failed to respond and those who were successfully treated with a proton pump inhibitor once daily. Am J Gastroenterol. 2009;104:2005–2013.
Tutuian R, Castell DO. Review article: complete gastro-oesophageal reflux monitoring—combined pH and impedance. Aliment Pharmacol Ther. 2006;24:27–37.
Pace F, Sangaletti O, Pallotta S, et al. Biliary reflux and non-acid reflux are two distinct phenomena: a comparison between 24-hour multichannel intraesophageal impedance and bilirubin monitoring. Scand J Gastroenterol. 2007;42:1031–1039.
Bredenoord AJ. Impedance-pH monitoring: new standard for measuring gastro-oesophageal reflux. Neurogastroenterol Motil. 2008;20:434–439.
Zerbib F, Roman S, Ropert A, et al. Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol. 2006;101:1956–1963.
Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut. 2006;55:1398–1402.
Sharma N, Agrawal A, Freeman J, Vela M, Castell DO. An analysis of persistent symptoms in acid-suppressed patients undergoing impedance-pH monitoring. Clin Gastroenterol Hepatol. 2008;6:521–524.
Savarino E, Zentilin P, Tutuian R, et al. Role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy. Am J Gastroenterol. 2008;103:2685–2693.
Savarino E, Marabotto E, Zentilin P, et al. The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease. Dig Liver Dis. 2011;43:542–547.
Slaughter JC, Goutte M, Rymer JA, et al. Caution about overinterpretation of symptom indexes in reflux monitoring for refractory gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2011;9:868–874.
Pritchett JM, Aslam M, Slaughter JC, Ness RM, Garrett CG, Vaezi MF. Efficacy of esophageal impedance/pH monitoring in patients with refractory gastroesophageal reflux disease, on and off therapy. Clin Gastroenterol Hepatol. 2009;7:743–748.
Frazzoni M, Conigliaro R, Mirante VG, Melotti G. The added value of quantitative analysis of on-therapy impedance-pH parameters in distinguishing refractory non-erosive reflux disease from functional heartburn. Neurogastroenterol Motil. 2012;24:141-e87.
Frazzoni M, Conigliaro R, Melotti G. Reflux parameters as modified by laparoscopic fundoplication in 40 patients with heartburn/regurgitation persisting despite PPI therapy. A study using impedance-pH monitoring. Dig Dis Sci. 2011;56:1099–1106.
Frazzoni M, Conigliaro R, Manta R, Melotti G. Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD. Aliment Pharmacol Ther. 2011;34:67–75.
Frazzoni M, Piccoli M, Conigliaro R, Manta R, Frazzoni L, Melotti G. Refractory gastroesophageal reflux disease as diagnosed by impedance-pH monitoring can be cured by laparoscopic fundoplication. Surg Endosc. 2013;27:2940–2946.
Helm J, Dodds W, Pelc L, Palmer DW, Hogan WJ, Teeter BC. Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med. 1984;310:284–288.
Shafik A, El-Sibai O, Shafik AA, Mostafa R. Effect of topical esophageal acidification on salivary secretion: identification of the mechanism of action. J Gastroenterol Hepatol. 2005;20:1935–1939.
Conchillo J, Smout A. Review article: intra-oesophageal impedance monitoring for the assessment of bolus transit and gastro-oesophageal reflux. Aliment Pharmacol Ther. 2009;29:3–14.
Gyawali CP. Redeeming clinical value of esophageal pH impedance monitoring. Clin Gastroenterol Hepatol. 2016;14:47–49.
Woodley FW, Fernandez F, Mousa H. Diurnal variation in the chemical clearance of acid gastroesophageal reflux in infants. Clin Gastroenterol Hepatol. 2007;5:37–43.
Frazzoni M, Manta R, Mirante VG, Conigliaro R, Frazzoni L, Melotti G. Esophageal chemical clearance is impaired in gastro-esophageal reflux disease—a 24 h impedance-pH monitoring assessment. Neurogastroenterol Motil. 2013;25:399-e295.
Bredenoord AJ, Weusten BLAM, Timmer R, Smout AJPM. Reproducibility of multichannel intraluminal electrical impedance monitoring of gastroesophageal reflux. Am J Gastroenterol. 2005;100:265–269.
Frazzoni M, Bertani H, Manta R, et al. Impairment of chemical clearance is relevant to the pathogenesis of refractory reflux oesophagitis. Dig Liver Dis. 2014;46:596–612.
Frazzoni M, Bertani H, Conigliaro R, Frazzoni L, Losi L, Melotti G. Neoplastic progression in short-segment Barrett’s oesophagus is associated with impairment of chemical clearance, but not inadequate acid suppression by proton pump inhibitor therapy. Aliment Pharmacol Ther. 2014;40:835–842.
Kessing BF, Bredenoord AJ, Weijenborg PW, Hemmink GJ, Loots CM, Smout AJ. Esophageal acid exposure decreases intraluminal baseline impedance. Am J Gastroenterol. 2011;106:2093–2097.
Farrè R, Blondeau K, Clement D, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011;60:885–892.
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.
De Bortoli N, Martinucci I, Savarino E, et al. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn. Clin Gastroenterol Hepatol. 2015;13:1082–1088.
Frazzoni M, Savarino E, De Bortoli N, et al. Analyses of the post-reflux swallow-induced peristaltic wave index and nocturnal baseline impedance parameters increase the diagnostic yield of patients with reflux disease. Clin Gastroenterol Hepatol. 2016;14:40–46.
Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F. Functional esophageal disorders. Gastroenterology. 2016;150:1368–1379.
Dent J, Vakil N, Jones R, et al. Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the diamond study. Gut. 2010;59:714–721.
Vela MF, Craft BM, Sharma N, Freeman J, Hazen-Martin D. Refractory heartburn: comparison of intercellular space diameter in documented GERD vs. functional heartburn. Am J Gastroenterol. 2011;106:844–850.
Savarino E, Zentilin P, Mastracci L, et al. Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol. 2013;48:473–482.
Frazzoni M, de Bortoli N, Frazzoni L, et al. Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn. J Gastroenterol. 2017;52:444–451.
Patel A, Wang D, Salnani N, Sayuk GS, Gyawali CP. Distal mean nocturnal baseline impedance on pH-impedance monitoring predicts reflux burden and symptomatic outcome in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2016;44:890–898.
Frazzoni M, De Bortoli N, Frazzoni L, et al. The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring. Neurogastroenterol Motil. 2017;29:e12947.
Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut. 2012;61:1340–1354.
Zerbib F, Sifrim D, Tutuian R, Attwood S, Lundell L. Modern medical and surgical management of difficult-to-treat GORD. United Eur Gastroenterol J. 2013;1:21–31.
Savarino V, Dulbecco P, Savarino E. Are proton pump inhibitors really so dangerous? Dig Liver Dis. 2016;48:851–859.
Ravi K, Katzka DA. Esophageal impedance monitoring: clinical pearls and pitfalls. Am J Gastroenterol. 2016;111:1245–1256.
Zhong C, Duan L, Wang K, et al. Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease. J Gastroenterol. 2013;48:601–610.
Kandulski A, Weigt J, Caro C, et al. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn. Clin Gastroenterol Hepatol. 2015;13:1075–1081.
Cho YK, Lee JS, Lee TH, et al. The relationship of the post-reflux swallow-induced peristaltic wave index and esophageal baseline impedance with gastroesophageal reflux disease symptoms. J Neurogastroenterol Motil. 2017;23:237–244.
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.
Ravi K, DeVault KR, Murray JA, Bouras EP, Francis D. Inter-observer agreement for multichannel intraluminal impedance-pH testing. Dis Esophagus. 2010;23:540–544.
Hemmink GJ, Bredenoord AJ, Aanen MC, Weusten BL, Timmer R, Smout AJ. Computer analysis of 24-h esophageal impedance signals. Scand J Gastroenterol. 2011;46:271–276.
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MF wrote the manuscript. N de B, LF, ST, VS, ES critically revised the manuscript.
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Frazzoni, M., de Bortoli, N., Frazzoni, L. et al. Impedance-pH Monitoring for Diagnosis of Reflux Disease: New Perspectives. Dig Dis Sci 62, 1881–1889 (2017). https://doi.org/10.1007/s10620-017-4625-8
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DOI: https://doi.org/10.1007/s10620-017-4625-8