Journal of Gastroenterology

, Volume 50, Issue 7, pp 735–743 | Cite as

Correlation between hypersensitivity induced by esophageal acid infusion and the baseline impedance level in patients with suspected gastroesophageal reflux

  • A. Young Seo
  • Cheol Min ShinEmail author
  • Nayoung Kim
  • Hyuk Yoon
  • Young Soo Park
  • Dong Ho Lee
Original Article—Alimentary Tract



To evaluate the relevance between the pH parameters and baseline impedance level or esophageal hypomotility in patients with suspected gastroesophageal reflux.


The recordings of 51 patients with heartburn, acid regurgitation, globus or noncardiac chest pain were analyzed. Evaluation included a 24-h multichannel intraluminal impedance-pH test while on off-proton pump inhibitor therapy over 1 week, high-resolution manometry and Bernstein test. Mean baseline impedance level at the most distal portion of the impedance channel was assessed manually. Esophageal hypomotility was evaluated using transitional zone defect (TZD) and distal break (DB) length measurement.


In the study subjects (n = 51), 6 had a DeMeester score of more than 14.7 and 14 had a positive symptom index. The Bernstein test was positive in ten patients. The baseline impedance level was inversely correlated with the acid exposure time % (r = −0.660, P < 0.001). Also, all reflux and weakly acid reflux time % measured by impedance monitoring showed a weak correlation with TZD + DB length (r = 0.327 and 0.324, P = 0.019 and 0.020, respectively). Although a positive Bernstein test has no relevance for the acid exposure time or acid-related symptoms as represented by the DeMeester score or symptom index, the baseline impedance level was significantly lower in patients with a positive Bernstein test than in those with a negative one (2,628.4 ± 862.7 vs. 1,752.2 ± 611.1 Ω, P = 0.004).


A lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.


Acid infusion test Impedance test Gastroesophageal reflux disease 



The authors are indebted to J. Patrick Barron, Professor Emeritus, Tokyo Medical University, and Adjunct Professor, Seoul National University Bundang Hospital, for his pro bono editing of this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2014_1013_MOESM1_ESM.tif (10.9 mb)
Figure S1. Measurement of the transition zone defect (TZD) and distal break (DB)length. TZD was measured as the length (y axis) in centimeters of the break between the skeletal and smooth muscle contraction segments in the 20-mmHg isobaric contour. DB was measured as the length in centimeters of a visible break at the distal pressure troughs in the 20-mmHg isobaric contour. (TIFF 11157 kb)
535_2014_1013_MOESM2_ESM.tif (7.2 mb)
Figure S2. Diagnosis of hiatal hernia using endoscopy or high-resolution manometry.Endoscopically, the gastroesophageal junction (EGJ) at 2 cm or more above the diaphragmatic pinchcock is considered as the presence of hiatal hernia (C). In high-resolution manometry, the two main EGJ components are a lower esophageal sphincter (LES) and crural diaphragm (CD). Type I: CD and LES are completely superimposed (D). Type II: minimal separation between CD and LES during inspiration (E). The nadir between two peaks remains above the gastric baseline pressure. Type III: wide separation between CD and LES (>2 cm, F) (TIFF 7403 kb)
535_2014_1013_MOESM3_ESM.tif (107 kb)
Figure S3. Time period selection for measurement of esophageal impedance baseline levels. Mean impedance value of the 12 selected periods was considered baseline impedance. (TIFF 108 kb)


  1. 1.
    Levin MDTR, Schmittdiel MAJA, Kunz MPPK, Henning MSJM, Henke CJ, Colby CJ, et al. Costs of acid-related disorders to a health maintenance organization. Am J Med. 1997;103(6):520–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Farré R, Fornari F, Blondeau K, Vieth M, De Vos R, Bisschops R, et al. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus. Gut. 2010;59(2):164–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Barlow WJ, Orlando RC. The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis. Gastroenterology. 2005;128(3):771–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Tobey NA, Carson JL, Alkiek RA, Orlando R. Dilated intercellular spaces: a morphological feature of acid reflux–damaged human esophageal epithelium. Gastroenterology. 1996;111(5):1200–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Caviglia R, Ribolsi M, Maggiano N, Gabbrielli AM, Emerenziani S, Guarino MPL, et al. Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure. Am J Gastroenterol. 2005;100(3):543–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Bredenoord AJ, Tutuian R, Smout AJ, Castell DO. Technology review: esophageal impedance monitoring. Am J Gastroenterol. 2007;102(1):187–94.PubMedCrossRefGoogle Scholar
  7. 7.
    Farré R, Blondeau K, Clement D, Vicario M, Cardozo L, Vieth M, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011;60(7):885–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Kessing BF, Bredenoord AJ, Weijenborg PW, Hemmink GJ, Loots CM, Smout A. Esophageal acid exposure decreases intraluminal baseline impedance levels. Am J Gastroenterol. 2011;106(12):2093–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Clouse RE, Prakash C. Topographic esophageal manometry: an emerging clinical and investigative approach. Dig Dis. 2000;18(2):64–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Ghosh S, Pandolfino J, Kwiatek M, Kahrilas P. Oesophageal peristaltic transition zone defects: real but few and far between. Neurogastroenterol Motil. 2008;20(12):1283–90.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Pohl D, Ribolsi M, Savarino E, Frühauf H, Fried M, Castell DO, et al. Characteristics of the esophageal low-pressure zone in healthy volunteers and patients with esophageal symptoms: assessment by high-resolution manometry. Am J Gastroenterol. 2008;103(10):2544–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Kumar N, Porter RF, Chanin JM, Gyawali CP. Analysis of intersegmental trough and proximal latency of smooth muscle contraction using high-resolution esophageal manometry. J Clin Gastroenterol. 2012;46(5):375–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Han MS, Lee H, Jo JH, Cho IR, Park JC, Shin SK, et al. Transition zone defect associated with the response to proton pump inhibitor treatment in patients with globus sensation. J Gastroenterol Hepatol. 2013;28(6):954–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Roman S, Lin Z, Kwiatek MA, Pandolfino JE, Kahrilas PJ. Weak peristalsis in esophageal pressure topography: classification and association with dysphagia. Am J Gastroenterol. 2010;106(2):349–56.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Pandolfino JE, Roman S. High-resolution manometry: an atlas of esophageal motility disorders and findings of GERD using esophageal pressure topography. Thorac Surg Clin. 2011;21(4):465–75.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Ho KY, Cheung TK, Wong BC. Gastroesophageal reflux disease in Asian countries: disorder of nature or nurture? J Gastroenterol Hepatol. 2006;21(9):1362–5.PubMedGoogle Scholar
  17. 17.
    Miwa H, Minoo T, Hojo M, Yaginuma R, Nagahara A, Kawabe M, et al. Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases. Aliment Pharmacol Ther. 2004;20(s1):112–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Lundell L, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45(2):172–80.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Bogte A, Bredenoord A, Oors J, Siersema P, Smout A. Normal values for esophageal high-resolution manometry. Neurogastroenterol Motil. 2013;25(9):762-e579.PubMedCrossRefGoogle Scholar
  20. 20.
    Bredenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout A. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography1. Neurogastroenterol Motil. 2012;24(s1):57–65.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Pandolfino JE, Kim H, Ghosh SK, Clarke JO, Zhang Q, Kahrilas PJ. High-resolution manometry of the EGJ: an analysis of crural diaphragm function in GERD. Am J Gastroenterol. 2007;102(5):1056–63.PubMedCrossRefGoogle Scholar
  22. 22.
    Zentilin P, Iiritano E, Dulbecco P, Bilardi C, Savarino E, De Conca S, et al. Normal values of 24-h ambulatory intraluminal impedance combined with pH-metry in subjects eating a Mediterranean diet. Dig Liv Dis. 2006;38(4):226–32.CrossRefGoogle Scholar
  23. 23.
    Wiener G, Richter J, Copper J, Wu W, Castell D. The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring. Am J Gastroenterol. 1988;83(4):358–61.PubMedGoogle Scholar
  24. 24.
    Jamieson JR, Stein HJ, DeMeester TR, Bonavina L, Schwizer W, Hinder RA, et al. Ambulatory 24-h esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility. Am J Gastroenterol. 1992;87:1102.PubMedGoogle Scholar
  25. 25.
    Vaezi MF, Richter JE. Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology. 1996;111(5):1192–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Farre R, van Malenstein H, De Vos R, Geboes K, Depoortere I, Berghe PV, et al. Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces. Gut. 2008;57(10):1366–74.PubMedCrossRefGoogle Scholar
  27. 27.
    Borrelli O, Salvatore S, Mancini V, Ribolsi M, Gentile M, Bizzarri B, et al. Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease. Neurogastroenterol Motil. 2012;24(9):828-e394.PubMedCrossRefGoogle Scholar
  28. 28.
    Bulsiewicz WJ, Kahrilas PJ, Kwiatek MA, Ghosh SK, Meek A, Pandolfino JE. Esophageal pressure topography criteria indicative of incomplete bolus clearance: a study using high-resolution impedance manometry. Am J Gastroenterol. 2009;104(11):2721–8.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Woodland P, Al-Zinaty M, Yazaki E, Sifrim D. In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease. Gut. 2013;62(9):1256–61.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • A. Young Seo
    • 1
    • 2
  • Cheol Min Shin
    • 1
    Email author
  • Nayoung Kim
    • 1
  • Hyuk Yoon
    • 1
  • Young Soo Park
    • 1
  • Dong Ho Lee
    • 1
  1. 1.Department of Internal MedicineSeoul National University Bundang HospitalSeongnamSouth Korea
  2. 2.Health Promotion Center, Samsung Changwon HospitalSungkyunkwan University School of MedicineChangwonKorea

Personalised recommendations