Skip to main content
SpringerLink
Log in

Nonerosive Reflux Disease (NERD)

  • Chapter
  • First Online:
Gastrointestinal Motility Disorders

  • 1319 Accesses

Abstract

Nonerosive reflux disease (NERD) is defined by typical gastroesophageal reflux-related symptoms, lack of endoscopic evidence of esophageal inflammation, and increased esophageal acid exposure. NERD is the most common phenotypic presentation of gastroesophageal reflux disease (GERD), accounting for up to 70% of all patients with heartburn symptoms. NERD also accounts for the majority of the GERD patients who failed proton pump inhibitor (PPI) treatment. There is a very low, if any, rate of progression from NERD to erosive esophagitis and Barrett’s esophagus. After initial normal endoscopic evaluation, pH testing is pivotal to the diagnosis of NERD and to distinguish the disorder from functional heartburn and reflux hypersensitivity. While not yet in clinical practice, mucosal impedance is a diagnostic tool that has been shown to be useful in diagnosing NERD patients including those who are refractory to PPI therapy already during endoscopy. Treatment focuses on acid suppression, but the proportion of NERD patients responding to a standard dose of PPI is significantly lower than what has been documented in patients with erosive esophagitis. Endoscopic therapy and antireflux surgery have been demonstrated to be efficacious in carefully selected NERD patients. Alternative therapeutic strategies consist of transient lower esophageal sphincter relaxation reducers, pain modulators, psychological intervention, acupuncture, and other alternative and complementary medicine approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, Global Consensus G. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–20; quiz 1943.

    Google Scholar 

  2. Fass R, Fennerty MB, Vakil N. Nonerosive reflux disease—current concepts and dilemmas. Am J Gastroenterol. 2001;96:303–14.

    CAS  PubMed  Google Scholar 

  3. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005;54:710–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Locke GR III, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997;112:1448–56.

    Article  PubMed  Google Scholar 

  5. Fock KM, Talley NJ, Fass R, et al. Asia-Pacific consensus on the management of gastroesophageal reflux disease: update. J Gastroenterol Hepatol. 2008;23:8–22.

    Article  PubMed  Google Scholar 

  6. Francis DO, Rymer JA, Slaughter JC, et al. High economic burden of caring for patients with suspected extraesophageal reflux. Am J Gastroenterol. 2013;108:905–11.

    Article  PubMed  Google Scholar 

  7. An evidence-based appraisal of reflux disease management—the Genval Workshop Report. Gut. 1999;44(Suppl 2):S1–16.

    Google Scholar 

  8. Fass R. Proton pump inhibitor failure—what are the therapeutic options? Am J Gastroenterol. 2009;104(Suppl 2):S33–8.

    Article  CAS  PubMed  Google Scholar 

  9. Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut. 2009;58:295–309.

    Article  CAS  PubMed  Google Scholar 

  10. Martinez SD, Malagon IB, Garewal HS, Cui H, Fass R. Non-erosive reflux disease (NERD)—acid reflux and symptom patterns. Aliment Pharmacol Ther. 2003;17:537–45.

    Article  CAS  PubMed  Google Scholar 

  11. Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006;15:237–41.

    PubMed  Google Scholar 

  12. Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F. Functional esophageal disorders. Gastroenterology. 2016;150:1368–79.

    Google Scholar 

  13. Winters C Jr, Spurling TJ, Chobanian SJ, et al. Barrett’s esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology. 1987;92:118–24.

    Article  PubMed  Google Scholar 

  14. Johansson KE, Ask P, Boeryd B, Fransson SG, Tibbling L. Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease. Scand J Gastroenterol. 1986;21:837–47.

    Article  CAS  PubMed  Google Scholar 

  15. Lind T, Havelund T, Carlsson R, et al. Heartburn without oesophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand J Gastroenterol. 1997;32:974–9.

    Article  CAS  PubMed  Google Scholar 

  16. Jones R. Gastro-oesophageal reflux disease in general practice. Scand J Gastroenterol Suppl. 1995;211:35–8.

    Article  CAS  PubMed  Google Scholar 

  17. Robinson M, Earnest D, Rodriguez-Stanley S, et al. Heartburn requiring frequent antacid use may indicate significant illness. Arch Intern Med. 1998;158:2373–6.

    Article  CAS  PubMed  Google Scholar 

  18. Ronkainen J, Aro P, Storskrubb T, et al. High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report. Scand J Gastroenterol. 2005;40:275–85.

    Article  PubMed  Google Scholar 

  19. Zagari RM, Fuccio L, Wallander MA, et al. Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano-Monghidoro study. Gut. 2008;57:1354–9.

    Article  CAS  PubMed  Google Scholar 

  20. El-Serag H. The association between obesity and GERD: a review of the epidemiological evidence. Dig Dis Sci. 2008;53:2307–12.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rosaida MS, Goh KL. Gastro-oesophageal reflux disease, reflux oesophagitis and non-erosive reflux disease in a multiracial Asian population: a prospective, endoscopy based study. Eur J Gastroenterol Hepatol. 2004;16:495–501.

    Article  PubMed  Google Scholar 

  22. Dore MP, Pes GM, Bassotti G, Farina MA, Marras G, Graham DY. Risk factors for erosive and non-erosive gastroesophageal reflux disease and Barrett’s esophagus in Nothern Sardinia. Scand J Gastroenterol. 2016;51:1281–7.

    Google Scholar 

  23. Quigley EM. Gastro-oesophageal reflux disease-spectrum or continuum? QJM. 1997;90:75–8.

    Article  CAS  PubMed  Google Scholar 

  24. Pace F, Santalucia F, Bianchi PG. Natural history of gastro-oesophageal reflux disease without oesophagitis. Gut. 1991;32:845–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kuster E, Ros E, Toledo-Pimentel V, et al. Predictive factors of the long term outcome in gastro-oesophageal reflux disease: six year follow up of 107 patients. Gut. 1994;35:8–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Isolauri J, Luostarinen M, Isolauri E, Reinikainen P, Viljakka M, Keyrilainen O. Natural course of gastroesophageal reflux disease: 17–22 year follow-up of 60 patients. Am J Gastroenterol. 1997;92:37–41.

    CAS  PubMed  Google Scholar 

  27. McDougall NI, Johnston BT, Collins JS, McFarland RJ, Love AH. Disease progression in gastro-oesophageal reflux disease as determined by repeat oesophageal pH monitoring and endoscopy 3 to 4.5 years after diagnosis. Eur J Gastroenterol Hepatol. 1997;9:1161–7.

    CAS  PubMed  Google Scholar 

  28. Ronkainen J, Talley NJ, Storskrubb T, et al. Erosive esophagitis is a risk factor for Barrett’s esophagus: a community-based endoscopic follow-up study. Am J Gastroenterol. 2011;106:1946–52.

    Article  PubMed  Google Scholar 

  29. Pace F, Bollani S, Molteni P, Bianchi PG. Natural history of gastro-oesophageal reflux disease without oesophagitis (NERD)—a reappraisal 10 years on. Dig Liver Dis. 2004;36:111–5.

    Article  CAS  PubMed  Google Scholar 

  30. Labenz J, Nocon M, Lind T, et al. Prospective follow-up data from the ProGERD study suggest that GERD is not a categorial disease. Am J Gastroenterol. 2006;101:2457–62.

    Article  PubMed  Google Scholar 

  31. Garrido Serrano A, Guerrero Igea FJ, Lepe Jimenez JA, Perianes Hernandez C. Clinical features and endoscopic progression of gastroesophageal reflux disease. Rev Esp Enferm Dig. 2003;95:712–6, 707–11.

    Google Scholar 

  32. Sontag SJ, Sonnenberg A, Schnell TG, Leya J, Metz A. The long-term natural history of gastroesophageal reflux disease. J Clin Gastroenterol. 2006;40:398–404.

    Article  PubMed  Google Scholar 

  33. Bardhan KD, Royston C, Nayyar AK. Reflux rising! An essay on witnessing a disease in evolution. Dig Liver Dis. 2006;38:163–8.

    Article  CAS  PubMed  Google Scholar 

  34. Lee YC, Yen AM, Tai JJ, et al. The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease. Gut. 2009;58:174–81.

    Article  PubMed  Google Scholar 

  35. Erichsen R, Robertson D, Farkas DK, et al. Erosive reflux disease increases risk for esophageal adenocarcinoma, compared with nonerosive reflux. Clin Gastroenterol Hepatol. 2012;10:475–80. e471

    Article  PubMed  Google Scholar 

  36. Hershcovici T, Fass R. Nonerosive reflux disease (NERD) - an update. J Neurogastroenterol Motil. 2010;16:8–21.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ho KY, Kang JY. Reflux esophagitis patients in Singapore have motor and acid exposure abnormalities similar to patients in the Western hemisphere. Am J Gastroenterol. 1999;94:1186–91.

    Article  CAS  PubMed  Google Scholar 

  38. Dickman R, Bautista JM, Wong WM, et al. Comparison of esophageal acid exposure distribution along the esophagus among the different gastroesophageal reflux disease (GERD) groups. Am J Gastroenterol. 2006;101:2463–9.

    Article  PubMed  Google Scholar 

  39. Shapiro M, Green C, Faybush EM, Esquivel RF, Fass R. The extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups. Aliment Pharmacol Ther. 2006;23:321–9.

    Article  CAS  PubMed  Google Scholar 

  40. Sano H, Iwakiri K, Kawami N, Tanaka Y, Sakamoto C. Mechanisms of acid reflux and how refluxed acid extends proximally in patients with non-erosive reflux disease. Digestion. 2014;90:108–15.

    Article  CAS  PubMed  Google Scholar 

  41. Bredenoord AJ, Hemmink GJ, Smout AJ. Relationship between gastro-oesophageal reflux pattern and severity of mucosal damage. Neurogastroenterol Motil. 2009;21:807–12.

    Article  CAS  PubMed  Google Scholar 

  42. Emerenziani S, Sifrim D, Habib FI, et al. Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus. Gut. 2008;57:443–7.

    Article  CAS  PubMed  Google Scholar 

  43. Adachi K, Fujishiro H, Katsube T, et al. Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis. J Gastroenterol Hepatol. 2001;16:1191–6.

    Article  CAS  PubMed  Google Scholar 

  44. Dickman R, Parthasarathy S, Malagon IB, et al. Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro-oesophageal reflux disease groups. Aliment Pharmacol Ther. 2007;26:41–8.

    Article  CAS  PubMed  Google Scholar 

  45. Bredenoord AJ, Weusten BL, Curvers WL, Timmer R, Smout AJ. Determinants of perception of heartburn and regurgitation. Gut. 2006;55:313–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Schey R, Shapiro M, Navarro-Rodriguez T, et al. Comparison of the different characteristics of sensed reflux events among different heartburn groups. J Clin Gastroenterol. 2009;43:699–704.

    Article  PubMed  Google Scholar 

  47. Emerenziani S, Ribolsi M, Sifrim D, Blondeau K, Cicala M. Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non-erosive reflux disease. Neurogastroenterol Motil. 2009;21:253–8.

    Article  CAS  PubMed  Google Scholar 

  48. Savarino E, Zentilin P, Tutuian R, et al. The role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy. Am J Gastroenterol. 2008;103:2685–93.

    Article  PubMed  Google Scholar 

  49. Farre R, Fornari F, Blondeau K, et al. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus. Gut. 2010;59:164–9.

    Article  PubMed  Google Scholar 

  50. Caviglia R, Ribolsi M, Maggiano N, et al. Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure. Am J Gastroenterol. 2005;100:543–8.

    Article  PubMed  Google Scholar 

  51. Farre R, Blondeau K, Clement D, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011;60:885–92.

    Article  PubMed  Google Scholar 

  52. Boeckxstaens GE, Smout A. Systematic review: role of acid, weakly acidic and weakly alkaline reflux in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2010;32:334–43.

    Article  CAS  PubMed  Google Scholar 

  53. Emerenziani S, Ribolsi M, Guarino MP, et al. Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients. Neurogastroenterol Motil. 2014;26:108–14.

    Article  CAS  PubMed  Google Scholar 

  54. Weijenborg PW, Bredenoord AJ. How reflux causes symptoms: reflux perception in gastroesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2013;27:353–64.

    Article  PubMed  Google Scholar 

  55. Bravi I, Woodland P, Gill RS, Al-Zinaty M, Bredenoord AJ, Sifrim D. Increased prandial air swallowing and postprandial gas-liquid reflux among patients refractory to proton pump inhibitor therapy. Clin Gastroenterol Hepatol. 2013;​11:784–9.

    Article  PubMed  Google Scholar 

  56. Vaezi MF, Richter JE. Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology. 1996;111:1192–9.

    Article  CAS  PubMed  Google Scholar 

  57. Iwakiri K, Hayashi Y, Kotoyori M, et al. Defective triggering of secondary peristalsis in patients with non-erosive reflux disease. J Gastroenterol Hepatol. 2007;22:2208–11.

    Article  PubMed  Google Scholar 

  58. Kahrilas PJ, Dodds WJ, Hogan WJ, Kern M, Arndorfer RC, Reece A. Esophageal peristaltic dysfunction in peptic esophagitis. Gastroenterology. 1986;91:897–904.

    Article  CAS  PubMed  Google Scholar 

  59. Cameron AJ. Barrett's esophagus: prevalence and size of hiatal hernia. Am J Gastroenterol. 1999;94:2054–9.

    Article  CAS  PubMed  Google Scholar 

  60. Lee SW, Lee TY, Lien HC, Yang SS, Yeh HZ, Chang CS. Characteristics of symptom presentation and risk factors in patients with erosive esophagitis and nonerosive reflux disease. Med Princ Pract. 2014;23:460–4.

    Article  PubMed  Google Scholar 

  61. van Herwaarden MA, Samsom M, Smout AJ. Excess gastroesophageal reflux in patients with hiatus hernia is caused by mechanisms other than transient LES relaxations. Gastroenterology. 2000;119:1439–46.

    Article  PubMed  Google Scholar 

  62. Weusten BL, Akkermans LM, vanBerge-Henegouwen GP, Smout AJ. Symptom perception in gastroesophageal reflux disease is dependent on spatiotemporal reflux characteristics. Gastroenterology. 1995;108:1739–44.

    Article  CAS  PubMed  Google Scholar 

  63. Calabrese C, Bortolotti M, Fabbri A, et al. Reversibility of GERD ultrastructural alterations and relief of symptoms after omeprazole treatment. Am J Gastroenterol. 2005;100:537–42.

    Article  CAS  PubMed  Google Scholar 

  64. Cui R, Zhou L, Lin S, et al. The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower-esophagus of GERD patients. Dis Esophagus. 2011;24:1–5.

    Article  CAS  PubMed  Google Scholar 

  65. Tobey NA, Carson JL, Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of acid reflux—damaged human esophageal epithelium. Gastroenterology. 1996;111:1200–5.

    Article  CAS  PubMed  Google Scholar 

  66. Knowles CH, Aziz Q. Visceral hypersensitivity in non-erosive reflux disease. Gut. 2008;57:674–83.

    Article  CAS  PubMed  Google Scholar 

  67. Miwa H, Minoo T, Hojo M, et al. Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases. Aliment Pharmacol Ther. 2004;20(Suppl 1):112–7.

    Article  PubMed  Google Scholar 

  68. Nagahara A, Miwa H, Minoo T, et al. Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease. J Clin Gastroenterol. 2006;40:891–5.

    Article  CAS  PubMed  Google Scholar 

  69. Reddy H, Staahl C, Arendt-Nielsen L, Gregersen H, Drewes AM, Funch-Jensen P. Sensory and biomechanical properties of the esophagus in non-erosive reflux disease. Scand J Gastroenterol. 2007;42:432–40.

    Article  PubMed  Google Scholar 

  70. Trimble KC, Pryde A, Heading RC. Lowered oesophageal sensory thresholds in patients with symptomatic but not excess gastro-oesophageal reflux: evidence for a spectrum of visceral sensitivity in GORD. Gut. 1995;37:7–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Anand P, Aziz Q, Willert R, van Oudenhove L. Peripheral and central mechanisms of visceral sensitization in man. Neurogastroenterol Motil. 2007;19:29–46.

    Article  CAS  PubMed  Google Scholar 

  72. Fass R, Naliboff BD, Fass SS, et al. The effect of auditory stress on perception of intraesophageal acid in patients with gastroesophageal reflux disease. Gastroenterology. 2008;134:696–705.

    Article  PubMed  Google Scholar 

  73. Bhat YM, Bielefeldt K. Capsaicin receptor (TRPV1) and non-erosive reflux disease. Eur J Gastroenterol Hepatol. 2006;18:263–70.

    Article  CAS  PubMed  Google Scholar 

  74. Sarkar S, Hobson AR, Hughes A, et al. The prostaglandin E2 receptor-1 (EP-1) mediates acid-induced visceral pain hypersensitivity in humans. Gastroenterology. 2003;124:18–25.

    Article  CAS  PubMed  Google Scholar 

  75. Ma J, Altomare A, Rieder F, Behar J, Biancani P, Harnett KM. ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa. Am J Physiol Gastrointest Liver Physiol. 2011;301:G1075–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Venables TL, Newland RD, Patel AC, Hole J, Wilcock C, Turbitt ML. Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice. Scand J Gastroenterol. 1997;32:965–73.

    Article  CAS  PubMed  Google Scholar 

  77. Carlsson R, Dent J, Watts R, et al. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group. Eur J Gastroenterol Hepatol. 1998;10:119–24.

    Article  CAS  PubMed  Google Scholar 

  78. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143:199–211.

    Article  PubMed  Google Scholar 

  79. Savarino E, Zentilin P, Marabotto E, et al. Overweight is a risk factor for both erosive and non-erosive reflux disease. Dig Liver Dis. 2011;43:940–5.

    Article  PubMed  Google Scholar 

  80. Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut. 2000;47:861–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Richter JE, Bradley LC. Psychophysiological interactions in esophageal diseases. Semin Gastrointest Dis. 1996;7:169–84.

    CAS  PubMed  Google Scholar 

  82. Nielzen S, Pettersson KI, Regnell G, Svensson R. The role of psychiatric factors in symptoms of hiatus hernia or gastric reflux. Acta Psychiatr Scand. 1986;73:214–20.

    Article  CAS  PubMed  Google Scholar 

  83. Lee YC, Wang HP, Chiu HM, et al. Comparative analysis between psychological and endoscopic profiles in patients with gastroesophageal reflux disease: a prospective study based on screening endoscopy. J Gastroenterol Hepatol. 2006;21:798–804.

    Article  PubMed  Google Scholar 

  84. Wu JC, Cheung CM, Wong VW, Sung JJ. Distinct clinical characteristics between patients with nonerosive reflux disease and those with reflux esophagitis. Clin Gastroenterol Hepatol. 2007;5:690–5.

    Article  PubMed  Google Scholar 

  85. Chen CL, Hsu PI. Current advances in the diagnosis and treatment of nonerosive reflux disease. Gastroenterol Res Pract. 2013;2013:653989.

    PubMed  PubMed Central  Google Scholar 

  86. Kahrilas PJ, Miner P, Johanson J, Mao L, Jokubaitis L, Sloan S. Efficacy of rabeprazole in the treatment of symptomatic gastroesophageal reflux disease. Dig Dis Sci. 2005;50:2009–18.

    Article  CAS  PubMed  Google Scholar 

  87. Zimmerman J, Hershcovici T. Bowel symptoms in nonerosive gastroesophageal reflux disease: nature, prevalence, and relation to acid reflux. J Clin Gastroenterol. 2008;42:261–5.

    PubMed  Google Scholar 

  88. Kusano M, Hosaka H, Kawamura O, et al. More severe upper gastrointestinal symptoms associated with non-erosive reflux disease than with erosive gastroesophageal reflux disease during maintenance proton pump inhibitor therapy. J Gastroenterol. 2015;50:298–304.

    Article  CAS  PubMed  Google Scholar 

  89. Hershcovici T, Zimmerman J. Functional heartburn vs. non-erosive reflux disease: similarities and differences. Aliment Pharmacol Ther. 2008;27:1103–9.

    Article  CAS  PubMed  Google Scholar 

  90. Mody R, Bolge SC, Kannan H, Fass R. Effects of gastroesophageal reflux disease on sleep and outcomes. Clin Gastroenterol Hepatol. 2009;7:953–9.

    Article  PubMed  Google Scholar 

  91. Kusano M, Kouzu T, Kawano T, Ohara S. Nationwide epidemiological study on gastroesophageal reflux disease and sleep disorders in the Japanese population. J Gastroenterol. 2008;43:833–41.

    Article  PubMed  Google Scholar 

  92. Yi CH, Hu CT, Chen CL. Sleep dysfunction in patients with GERD: erosive versus nonerosive reflux disease. Am J Med Sci. 2007;334:168–70.

    Article  PubMed  Google Scholar 

  93. You CR, Oh JH, Seo M, et al. Association between non-erosive reflux disease and high risk of obstructive sleep apnea in Korean population. J Neurogastroenterol Motil. 2014;20:197–204.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med. 2004;140:518–27.

    Article  CAS  PubMed  Google Scholar 

  95. Johnston BT, Troshinsky MB, Castell JA, Castell DO. Comparison of barium radiology with esophageal pH monitoring in the diagnosis of gastroesophageal reflux disease. Am J Gastroenterol. 1996;91:1181–5.

    CAS  PubMed  Google Scholar 

  96. Richter JE, Castell DO. Gastroesophageal reflux. Pathogenesis, diagnosis, and therapy. Ann Intern Med. 1982;97:93–103.

    Article  CAS  PubMed  Google Scholar 

  97. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45:172–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Arora AS. Management strategies for dysphagia with a normal-appearing esophagus. Clin Gastroenterol Hepatol. 2005;3:299–302.

    Article  PubMed  Google Scholar 

  99. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342–63.

    Article  CAS  PubMed  Google Scholar 

  100. Hershcovici T, Fass R. Step-by-step management of refractory gastresophageal reflux disease. Dis Esophagus. 2013;26:27–36.

    Article  CAS  PubMed  Google Scholar 

  101. Fiocca R, Mastracci L, Engstrom C, et al. Long-term outcome of microscopic esophagitis in chronic GERD patients treated with esomeprazole or laparoscopic antireflux surgery in the LOTUS trial. Am J Gastroenterol. 2010;105:1015–23.

    Article  CAS  PubMed  Google Scholar 

  102. Kandulski A, Jechorek D, Caro C, et al. Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn. Aliment Pharmacol Ther. 2013;38:643–51.

    Article  CAS  PubMed  Google Scholar 

  103. Kiesslich R, Kanzler S, Vieth M, et al. Minimal change esophagitis: prospective comparison of endoscopic and histological markers between patients with non-erosive reflux disease and normal controls using magnifying endoscopy. Dig Dis. 2004;22:221–7.

    Article  CAS  PubMed  Google Scholar 

  104. Kiesslich R, Fritsch J, Holtmann M, et al. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology. 2003;124:880–8.

    Article  PubMed  Google Scholar 

  105. Yoshikawa I, Yamasaki M, Yamasaki T, Kume K, Otsuki M. Lugol chromoendoscopy as a diagnostic tool in so-called endoscopy-negative GERD. Gastrointest Endosc. 2005;62:698–703; quiz 752, 754.

    Google Scholar 

  106. Gabbard SL, Fass R, Maradey-Romero C, Gingold Belfer R, Dickman R. Identifying minimal changes in nonerosive reflux disease: is the pay worth the labor? J Clin Gastroenterol. 2016;50:11–6.

    Article  PubMed  Google Scholar 

  107. Sharma P, Wani S, Bansal A, et al. A feasibility trial of narrow band imaging endoscopy in patients with gastroesophageal reflux disease. Gastroenterology. 2007;133:454–64; quiz 674.

    Google Scholar 

  108. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308–28; quiz 329.

    Google Scholar 

  109. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology. 2008;135:1383–91, 1391, e1381–5.

    Google Scholar 

  110. Kandulski A, Weigt J, Caro C, Jechorek D, Wex T, Malfertheiner P. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn. Clin Gastroenterol Hepatol. 2015;13:1075–81.

    Article  PubMed  Google Scholar 

  111. Saritas Yuksel E, Higginbotham T, Slaughter JC, et al. Use of direct, endoscopic-guided measurements of mucosal impedance in diagnosis of gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2012;10:1110–6.

    Article  PubMed  Google Scholar 

  112. Ates F, Yuksel ES, Higginbotham T, et al. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology. 2015;148:334–43.

    Article  PubMed  Google Scholar 

  113. van Pinxteren B, Numans ME, Bonis PA, Lau J. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2006;19:CD002095.

    Google Scholar 

  114. Bate CM, Griffin SM, Keeling PW, et al. Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis. Aliment Pharmacol Ther. 1996;10:547–55.

    Article  CAS  PubMed  Google Scholar 

  115. Miner P Jr, Orr W, Filippone J, Jokubaitis L, Sloan S. Rabeprazole in nonerosive gastroesophageal reflux disease: a randomized placebo-controlled trial. Am J Gastroenterol. 2002;97:1332–9.

    Article  CAS  PubMed  Google Scholar 

  116. Calabrese C, Liguori G, Gabusi V, et al. Ninety-six-hour wireless oesophageal pH monitoring following proton pump inhibitor administration in NERD patients. Aliment Pharmacol Ther. 2008;28:250–5.

    Article  CAS  PubMed  Google Scholar 

  117. Katz PO, Castell DO, Levine D. Esomeprazole resolves chronic heartburn in patients without erosive oesophagitis. Aliment Pharmacol Ther. 2003;18:875–82.

    Article  CAS  PubMed  Google Scholar 

  118. Fass R, Chey WD, Zakko SF, et al. Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2009;29:1261–72.

    Article  CAS  PubMed  Google Scholar 

  119. Wu MS, Tan SC, Xiong T. Indirect comparison of randomised controlled trials: comparative efficacy of dexlansoprazole vs. esomeprazole in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2013;38:190–201.

    Article  CAS  PubMed  Google Scholar 

  120. Hershcovici T, Fass R. An algorithm for diagnosis and treatment of refractory GERD. Best Pract Res Clin Gastroenterol. 2010;24:923–36.

    Article  PubMed  Google Scholar 

  121. Wiklund I, Bardhan KD, Muller-Lissner S, et al. Quality of life during acute and intermittent treatment of gastro-oesophageal reflux disease with omeprazole compared with ranitidine. Results from a multicentre clinical trial. The European Study Group. Ital J Gastroenterol Hepatol. 1998;​30:19–27.

    CAS  PubMed  Google Scholar 

  122. Gerson LB, Robbins AS, Garber A, Hornberger J, Triadafilopoulos G. A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease. Am J Gastroenterol. 2000;95:395–407.

    Article  CAS  PubMed  Google Scholar 

  123. Juul-Hansen P, Rydning A. On-demand requirements of patients with endoscopy-negative gastro-oesophageal reflux disease: H2-blocker vs. proton pump inhibitor. Aliment Pharmacol Ther. 2009;29:207–12.

    Article  CAS  PubMed  Google Scholar 

  124. Bytzer P, Blum A, De Herdt D, Dubois D, Trial I. Six-month trial of on-demand rabeprazole 10 mg maintains symptom relief in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2004;20:181–8.

    Article  CAS  PubMed  Google Scholar 

  125. Bytzer P, Blum AL. Personal view: rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2004;20:389–98.

    Article  CAS  PubMed  Google Scholar 

  126. Kobeissy AA, Hashash JG, Jamali FR, et al. A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients with non-erosive reflux disease. World J Gastroenterol. 2012;18:2390–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Nagahara A, Hojo M, Asaoka D, Sasaki H, Watanabe S. A randomized prospective study comparing the efficacy of on-demand therapy versus continuous therapy for 6 months for long-term maintenance with omeprazole 20 mg in patients with gastroesophageal reflux disease in Japan. Scand J Gastroenterol. 2014;49:409–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Shi Y, Tan N, Zhang N, et al. Predictors of proton pump inhibitor failure in non-erosive reflux disease: a study with impedance-pH monitoring and high-resolution manometry. Neurogastroenterol Motil. 2016;28:674–9.

    Article  CAS  PubMed  Google Scholar 

  129. Dean BB, Gano AD Jr, Knight K, Ofman JJ, Fass R. Effectiveness of proton pump inhibitors in nonerosive reflux disease. Clin Gastroenterol Hepatol. 2004;2:656–64.

    Article  CAS  PubMed  Google Scholar 

  130. Richter JE, Campbell DR, Kahrilas PJ, Huang B, Fludas C. Lansoprazole compared with ranitidine for the treatment of nonerosive gastroesophageal reflux disease. Arch Intern Med. 2000;160:1803–9.

    Article  CAS  PubMed  Google Scholar 

  131. Fass R, Shapiro M, Dekel R, Sewell J. Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease—where next? Aliment Pharmacol Ther. 2005;22:79–94.

    Article  CAS  PubMed  Google Scholar 

  132. Van Soest EM, Siersema PD, Dieleman JP, Sturkenboom MC, Kuipers EJ. Persistence and adherence to proton pump inhibitors in daily clinical practice. Aliment Pharmacol Ther. 2006;24:377–85.

    Article  PubMed  CAS  Google Scholar 

  133. Gunaratnam NT, Jessup TP, Inadomi J, Lascewski DP. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006;23:1473–7.

    Article  CAS  PubMed  Google Scholar 

  134. Modlin IM, Hunt RH, Malfertheiner P, et al. Diagnosis and management of non-erosive reflux disease—the Vevey NERD Consensus Group. Digestion. 2009;80:74–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med. 2006;166:965–71.

    Article  PubMed  Google Scholar 

  136. Zhang Q, Lehmann A, Rigda R, Dent J, Holloway RH. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut. 2002;50:19–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Lidums I, Lehmann A, Checklin H, Dent J, Holloway RH. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology. 2000;118:7–13.

    Article  CAS  PubMed  Google Scholar 

  138. Manabe N, Haruma K, Ito M, et al. Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial. Dis Esophagus. 2012;25:373–80.

    Article  CAS  PubMed  Google Scholar 

  139. Chiu CT, Hsu CM, Wang CC, et al. Randomised clinical trial: sodium alginate oral suspension is non-inferior to omeprazole in the treatment of patients with non-erosive gastroesophageal disease. Aliment Pharmacol Ther. 2013;38:1054–64.

    Article  CAS  PubMed  Google Scholar 

  140. Ueda F, Watanabe M, Hirata Y, Kyoi T, Kimura K. Changes in cyclic AMP content of rat gastric mucosa induced by ulcerogenic stimuli—in relation to the antiulcer activity of irsogladine maleate. Jpn J Pharmacol. 1991;55:493–9.

    Article  CAS  PubMed  Google Scholar 

  141. Suzuki T, Matsushima M, Masui A, et al. Irsogladine maleate and rabeprazole in non-erosive reflux disease: a double-blind, placebo-controlled study. World J Gastroenterol. 2015;21:5023–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Tominaga K, Iwakiri R, Fujimoto K, et al. Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan. J Gastroenterol. 2012;47:284–92.

    Article  CAS  PubMed  Google Scholar 

  143. Campos GM, Peters JH, DeMeester TR, et al. Multivariate analysis of factors predicting outcome after laparoscopic Nissen fundoplication. J Gastrointest Surg. 1999;3:292–300.

    Article  CAS  PubMed  Google Scholar 

  144. Broeders JA, Draaisma WA, Bredenoord AJ, Smout AJ, Broeders IA, Gooszen HG. Long-term outcome of Nissen fundoplication in non-erosive and erosive gastro-oesophageal reflux disease. Br J Surg. 2010;97:845–52.

    Article  CAS  PubMed  Google Scholar 

  145. Lord RV, DeMeester SR, Peters JH, et al. Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease. J Gastrointest Surg. 2009;13:602–10.

    Article  PubMed  Google Scholar 

  146. Omura N, Kashiwagi H, Yano F, et al. Therapeutic effects of laparoscopic fundoplication for nonerosive gastroesophageal reflux disease. Surg Today. 2006;36:954–60.

    Article  PubMed  Google Scholar 

  147. Bonavina L, Saino GI, Bona D, et al. Magnetic augmentation of the lower esophageal sphincter: results of a feasibility clinical trial. J Gastrointest Surg. 2008;12:2133–40.

    Article  PubMed  Google Scholar 

  148. Fass R. Alternative therapeutic approaches to chronic proton pump inhibitor treatment. Clin Gastroenterol Hepatol. 2012;10:338–45; quiz e339–40.

    Google Scholar 

  149. Lipham JC, DeMeester TR, Ganz RA, et al. The LINX(R) reflux management system: confirmed safety and efficacy now at 4 years. Surg Endosc. 2012;26:2944–9.

    Article  PubMed  Google Scholar 

  150. Sheu EG, Nau P, Nath B, Kuo B, Rattner DW. A comparative trial of laparoscopic magnetic sphincter augmentation and Nissen fundoplication. Surg Endosc. 2015;29:505–9.

    Article  PubMed  Google Scholar 

  151. Warren HF, Reynolds JL, Lipham JC, et al. Multi-institutional outcomes using magnetic sphincter augmentation versus Nissen fundoplication for chronic gastroesophageal reflux disease. Surg Endosc. 2016;30:3289–96.

    Article  PubMed  Google Scholar 

  152. Leeds S, Reavis K. Endolumenal therapies for gastroesophageal reflux disease. Gastrointest Endosc Clin N Am. 2013;23:41–51.

    Article  PubMed  Google Scholar 

  153. Arts J, Sifrim D, Rutgeerts P, Lerut A, Janssens J, Tack J. Influence of radiofrequency energy delivery at the gastroesophageal junction (the Stretta procedure) on symptoms, acid exposure, and esophageal sensitivity to acid perfusion in gastroesophagal reflux disease. Dig Dis Sci. 2007;52:2170–7.

    Article  CAS  PubMed  Google Scholar 

  154. Noar MD, Lotfi-Emran S. Sustained improvement in symptoms of GERD and antisecretory drug use: 4-year follow-up of the Stretta procedure. Gastrointest Endosc. 2007;65:367–72.

    Article  PubMed  Google Scholar 

  155. Noar M, Squires P, Noar E, Lee M. Long-term maintenance effect of radiofrequency energy delivery for refractory GERD: a decade later. Surg Endosc. 2014;28:2323–33.

    Article  PubMed  Google Scholar 

  156. Franciosa M, Mashimo H. Stretta radiofrequency treatment for GERD: a safe and effective modality. Am J Gastroenterol. 2013;108:1654–5.

    Article  CAS  PubMed  Google Scholar 

  157. Cadiere GB, Rajan A, Rqibate M, et al. Endoluminal fundoplication (ELF)—evolution of EsophyX, a new surgical device for transoral surgery. Minim Invasive Ther Allied Technol. 2006;15:348–55.

    Article  CAS  PubMed  Google Scholar 

  158. Cadiere GB, Rajan A, Germay O, Himpens J. Endoluminal fundoplication by a transoral device for the treatment of GERD: a feasibility study. Surg Endosc. 2008;22:333–42.

    Article  CAS  PubMed  Google Scholar 

  159. Bell RC, Freeman KD. Clinical and pH-metric outcomes of transoral esophagogastric fundoplication for the treatment of gastroesophageal reflux disease. Surg Endosc. 2011;25:1975–84.

    Article  PubMed  Google Scholar 

  160. Cadiere GB, Buset M, Muls V, et al. Antireflux transoral incisionless fundoplication using EsophyX: 12-month results of a prospective multicenter study. World J Surg. 2008;32:1676–88.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Hoppo T, Immanuel A, Schuchert M, et al. Transoral incisionless fundoplication 2.0 procedure using EsophyX for gastroesophageal reflux disease. J Gastrointest Surg. 2010;14:1895–901.

    Article  PubMed  Google Scholar 

  162. Testoni PA, Testoni S, Mazzoleni G, Vailati C, Passaretti S. Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study. Surg Endosc. 2015;29:​2770–80.

    Article  PubMed  Google Scholar 

  163. Wendling MR, Melvin WS, Perry KA. Impact of transoral incisionless fundoplication (TIF) on subjective and objective GERD indices: a systematic review of the published literature. Surg Endosc. 2013;27:3754–61.

    Article  PubMed  Google Scholar 

  164. Hunter JG, Kahrilas PJ, Bell RC, et al. Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial. Gastroenterology. 2015;148:324–33. e325

    Article  CAS  PubMed  Google Scholar 

  165. Trad KS, Barnes WE, Simoni G, et al. Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO Randomized Clinical Trial. Surg Innov. 2015;22:26–40.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Topuz U, Umutoglu T, Bakan M, Ozturk E. Anesthetic management of the SRS Endoscopic Stapling System for gastro-esophageal reflux disease. World J Gastroenterol. 2013;19:319–20.

    Article  PubMed  PubMed Central  Google Scholar 

  167. Danalioglu A, Cipe G, Toydemir T, et al. Endoscopic stapling in comparison to laparoscopic fundoplication for the treatment of gastroesophageal reflux disease. Dig Endosc. 2014;26:37–42.

    Article  PubMed  Google Scholar 

  168. Inoue H, Ito H, Ikeda H, et al. Anti-reflux mucosectomy for gastroesophageal reflux disease in the absence of hiatus hernia: a pilot study. Ann Gastroenterol. 2014;27:346–51.

    PubMed  PubMed Central  Google Scholar 

  169. Doraiswamy PM, Varia I, Hellegers C, et al. A randomized controlled trial of paroxetine for noncardiac chest pain. Psychopharmacol Bull. 2006;39:15–24.

    PubMed  Google Scholar 

  170. Lee H, Kim JH, Min BH, et al. Efficacy of venlafaxine for symptomatic relief in young adult patients with functional chest pain: a randomized, double-blind, placebo-controlled, crossover trial. Am J Gastroenterol. 2010;105:1504–12.

    Article  CAS  PubMed  Google Scholar 

  171. Park SW, Lee H, Lee HJ, et al. Low-dose amitriptyline combined with proton pump inhibitor for functional chest pain. World J Gastroenterol. 2013;19:4958–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Mizyed I, Fass SS, Fass R. Review article: gastro-oesophageal reflux disease and psychological comorbidity. Aliment Pharmacol Ther. 2009;29:351–8.

    Article  CAS  PubMed  Google Scholar 

  173. Rubenstein JH, Nojkov B, Korsnes S, et al. Oesophageal hypersensitivity is associated with features of psychiatric disorders and the irritable bowel syndrome. Aliment Pharmacol Ther. 2007;26:443–52.

    Article  CAS  PubMed  Google Scholar 

  174. Nojkov B, Rubenstein JH, Adlis SA, et al. The influence of co-morbid IBS and psychological distress on outcomes and quality of life following PPI therapy in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2008;​27:473–82.

    Article  CAS  PubMed  Google Scholar 

  175. Kessing BF, Bredenoord AJ, Saleh CM, Smout AJ. Effects of anxiety and depression in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2015;13:1089–95. e1081

    Article  PubMed  Google Scholar 

  176. Kamolz T, Granderath FA, Bammer T, Pasiut M, Pointner R. Psychological intervention influences the outcome of laparoscopic antireflux surgery in patients with stress-related symptoms of gastroesophageal reflux disease. Scand J Gastroenterol. 2001;36:800–5.

    Article  CAS  PubMed  Google Scholar 

  177. Gordon A, Gordon E, Berelowitz M, Bremner CH, Bremner CG. Biofeedback improvement of lower esophageal sphincter pressures and reflux symptoms. J Clin Gastroenterol. 1983;5:235–7.

    Article  CAS  PubMed  Google Scholar 

  178. Shay SS, Johnson LF, Wong RK, et al. Rumination, heartburn, and daytime gastroesophageal reflux. A case study with mechanisms defined and successfully treated with biofeedback therapy. J Clin Gastroenterol. 1986;8:115–26.

    Article  CAS  PubMed  Google Scholar 

  179. Klein KB, Spiegel D. Modulation of gastric acid secretion by hypnosis. Gastroenterology. 1989;​96:1383–7.

    Article  CAS  PubMed  Google Scholar 

  180. Stacher G, Berner P, Naske R, et al. Effect of hypnotic suggestion of relaxation on basal and betazole-stimulated gastric acid secretion. Gastroenterology. 1975;68:656–61.

    CAS  PubMed  Google Scholar 

  181. Colgan SM, Faragher EB, Whorwell PJ. Controlled trial of hypnotherapy in relapse prevention of duodenal ulceration. Lancet. 1988;1:1299–300.

    Article  CAS  PubMed  Google Scholar 

  182. Riehl ME, Keefer L. Hypnotherapy for esophageal disorders. Am J Clin Hypn. 2015;58:22–33.

    Article  PubMed  PubMed Central  Google Scholar 

  183. McDonald-Haile J, Bradley LA, Bailey MA, Schan CA, Richter JE. Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux disease. Gastroenterology. 1994;107:61–9.

    Article  CAS  PubMed  Google Scholar 

  184. Diehl DL. Acupuncture for gastrointestinal and hepatobiliary disorders. J Altern Complement Med. 1999;5:27–45.

    Article  CAS  PubMed  Google Scholar 

  185. Samuels N. Acupuncture for nausea: how does it work? Harefuah. 2003;142:297–300, 316.

    Google Scholar 

  186. Dickman R, Schiff E, Holland A, et al. Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn. Aliment Pharmacol Ther. 2007;26:1333–44.

    Article  CAS  PubMed  Google Scholar 

  187. Zhang CX, Qin YM, Guo BR. Clinical study on the treatment of gastroesophageal reflux by acupuncture. Chin J Integr Med. 2010;16:298–303.

    Article  PubMed  Google Scholar 

  188. Zhang C, Guo L, Guo X, Guo X, Li G. Clinical curative effect of electroacupuncture combined with zhizhukuanzhong capsules for treating gastroesophageal reflux disease. J Tradit Chin Med. 2012;32:364–71.

    Article  PubMed  Google Scholar 

  189. Soffer E, Rodriguez L, Rodriguez P, Gomez B, Neto MG, Crowell MD. Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors. World J Gastrointest Pharmacol Ther. 2016;7:145–55.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Cleveland, OH, USA

    Jason Abdallah M.D.

  2. Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Ronnie Fass M.D.

Authors
  1. Jason Abdallah M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronnie Fass M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronnie Fass M.D. .

Editor information

Editors and Affiliations

  1. Institute of Gastroenterology, Sheba medical Center, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel

    Eytan Bardan

  2. Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Reza Shaker

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Abdallah, J., Fass, R. (2018). Nonerosive Reflux Disease (NERD). In: Bardan, E., Shaker, R. (eds) Gastrointestinal Motility Disorders . Springer, Cham. https://doi.org/10.1007/978-3-319-59352-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-59352-4_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-59350-0

  • Online ISBN: 978-3-319-59352-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation