Skip to main content
SpringerLink
Log in

Functional heartburn, nonerosive reflux disease, and reflux esophagitis are all distinct conditions—A debate: Pro

  • Published:
Current GERD Reports

Abstract

Gastroesophageal reflux disease (GERD) traditionally has been approached as a spectrum-continuum, in which patients may progress over time and develop more severe esophageal mucosal involvement. The spectrum-continuum conceptual model has profoundly affected research priorities, proposed diagnostic algorithms, and therapeutic strategies. Natural-course studies in GERD are almost always retrospective and commonly have many shortcomings: index endoscopy results are taken at face value; antireflux treatment is consumed until index endoscopy, during the followup phase, or both; pathophysiologic, anatomic, and genetic factors are overlooked; and confirmation of the durability of the new esophageal mucosal finding is lacking. Functional heartburn is common and is likely to affect a large subset of patients presenting with heartburn. Evidence to support the progression of functional heartburn to nonerosive reflux disease (NERD), erosive esophagitis, or Barrett’s esophagus is very scarce. The natural-course studies with the largest population or the longest duration report that only 10% of patients progress from NERD to erosive esophagitis. The other patients remain within their respective phenotypic presentations of GERD.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Spechler S, Goyal R: Barrett’s esophagus. N Engl J Med 1986, 315:362–371.

    Article  PubMed  CAS  Google Scholar 

  2. Labenz J, Jaspersen D, Kulig M, et al.: Risk factors for erosive esophagitis: a multivariate analysis based on the ProGERD study initiative. Am J Gastroenterol 2004, 99:1652–1656.

    Article  PubMed  Google Scholar 

  3. Fass R, Ofman J: Gastroesophageal reflux disease—should we adopt a new conceptual framework? Am J Gastroenterol 2002, 97:1901–1909.

    PubMed  Google Scholar 

  4. Fass R: Gastroesophageal reflux disease revisited. Gastroenterol Clin North Am 2002, 31:S1–S10.

    Article  PubMed  Google Scholar 

  5. Fass R: Distinct phenotypic presentations of gastroesophageal reflux disease: a new view of the natural history. Dig Dis 2004, 22:100–107.

    Article  PubMed  Google Scholar 

  6. Pace F, Bianchi Porro G: Gastroesophageal reflux disease: a typical spectrum disease (a new conceptual framework is not needed). Am J Gastroenterol 2004, 99:946–949.

    Article  PubMed  CAS  Google Scholar 

  7. Quigley E: Non-erosive reflux disease: a part of the spectrum of gastro-oesophageal reflux disease, a component of functional dyspepsia, or both? Eur J Gastroenterol Hepatol 2001, 13(Suppl 1):S13–S18.

    PubMed  Google Scholar 

  8. Agrawal A, Castell D: GERD is chronic but not progressive [editorial]. J Clin Gastroenterol 2006, 40:374–375.

    Article  PubMed  Google Scholar 

  9. Kaltenbach T, Crockett S, Gerson L: Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med 2006, 166:965–971.

    Article  PubMed  Google Scholar 

  10. Hanna S, Rastogi A, Weston A, et al.: Detection of Barrett’s esophagus after endoscopic healing of crosive esophagitis. Am J Gastroenterol 2006, 101:1416–1420.

    Article  PubMed  Google Scholar 

  11. Pace F, Bollani S, Molteni P, Bianchi Porro G: Natural history of gastro-oesophageal reflux disease without oesophagitis (NERD)—a reappraisal 10 years on. Dig Liver Dis 2004, 36:111–115.

    Article  PubMed  CAS  Google Scholar 

  12. Pace F, Pallotta S, Molteni P, et al.: Natural history of NERD in 3 Italian tertiary referral centres after 5 years of follow-up [abstract]. Gut 2006, 55(Suppl 5):A62.

    Google Scholar 

  13. Shapiro M, Green C, Faybush E, et al.: The extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups. Aliment Pharmacol Ther 2006, 23:321–329.

    Article  PubMed  CAS  Google Scholar 

  14. Fass R: Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol 2007, 41:131–137.

    Article  PubMed  Google Scholar 

  15. Klinkenberg-Knol E, Castell D: Clinical spectrum and diagnosis of gastroesophageal reflux disease. In The Esophagus, edn 2. Edited by Castell D, Richter J. Philadelphia: Lippincott Williams & Wilkins; 1999:435–442.

    Google Scholar 

  16. Lind T, Havelund T, Carlsson R, et al.: Heartburn without oesophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand J Gastroenterol 1997, 32:974–979.

    Article  PubMed  CAS  Google Scholar 

  17. Fass R, Fennerty M, Vakil N: Nonerosive reflux disease—current concepts and dilemmas. Am J Gastroenterol 2001, 96:303–314.

    PubMed  CAS  Google Scholar 

  18. Schenk B, Kuipers E, Klinkenberg-Knol E: Omeprazole as a diagnostic tool in gastroesophageal reflux disease. Am J Gastroenterol 1997, 92:1997–2000.

    PubMed  CAS  Google Scholar 

  19. Johnsson F, Weywadt L, Solhaug J, et al.: One-week omeprazole treatment in the diagnosis of gastro-oesophageal reflux disease. Scand J Gastroenterol 1998, 33:15–20.

    Article  PubMed  CAS  Google Scholar 

  20. Fass R, Ofman J, Gralnek I, et al.: Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease. Arch Intern Med 1999, 159:2161–2168.

    Article  PubMed  CAS  Google Scholar 

  21. Fass R, Tougas G: Functional heartburn: the stimulus, the pain, and the brain. Gut 2002, 51:885–892.

    Article  PubMed  CAS  Google Scholar 

  22. Hobson A, Matthews P, Furlong P, Aziz Q: The role of esophageal afferent pathway sensitivity in non-erosive reflux disease [abstract]. Gastroenterology 2004, 126:128.

    Google Scholar 

  23. Young M, Li ZS, Xu XR, et al.: Characterization of cortical potentials evoked by esophageal balloon distention and acid perfusion in patients with functional heartburn. Neurogastroenterol Motil 2006, 18:292–299.

    Article  Google Scholar 

  24. Rodriguez-Stanley S, Robinson M, Earnest D, et al.: Esophageal hypersensitivity may be a major cause of heartburn. Am J Gastroenterol 1999, 94:628–631.

    Article  PubMed  CAS  Google Scholar 

  25. Shapiro M, Green C, Bautista J, et al.: Functional heartburn patients demonstrate traits of functional bowel disorder but lack a uniform increase of chemoreceptor sensitivity to acid. Am J Gastroenterol 2006, 101:1084–1091.

    Article  PubMed  Google Scholar 

  26. Frazzoni M, De Micheli E, Zentilin P, Savarino V: Pathophysiological characteristics of patients with non-erosive reflux disease differ from those of patients with functional heartburn. Aliment Pharmacol Ther 2004, 20:81–88.

    Article  PubMed  CAS  Google Scholar 

  27. Martinez SD, Malagon IB, Garewal HS, et al.: Non-erosive reflux disease (NERD)—acid reflux and symptom patterns. Aliment Pharmacol Ther 2003, 17:537–545.

    Article  PubMed  CAS  Google Scholar 

  28. Cicala M, Emerenziani S, Caviglia R, et al.: Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2003, 18:605–613.

    Article  PubMed  CAS  Google Scholar 

  29. Prakash C, Clouse R: Value of extended recording time with wireless pH monitoring in evaluating gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2005, 3:329–334.

    Article  PubMed  Google Scholar 

  30. Lee YC, Wang HP, Chiu HM, et al.: Patients with functional heartburn are more likely to report retrosternal discomfort during wireless pH monitoring. Gastrointest Endosc 2005, 62:834–841.

    Article  PubMed  Google Scholar 

  31. 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, 100:543–548.

    Article  PubMed  Google Scholar 

  32. Schindlbeck N, Wiebecke B, Klauser A, et al.: Diagnostic value of histology in non-erosive gastrooesophageal reflux disease. Gut 1996, 39:151–154.

    Article  PubMed  CAS  Google Scholar 

  33. Pace F, Santalucia F, Bianchi Porro G: Natural history of gastro-oesophageal reflux disease without oesophagitis. Gut 1991, 32:845–848.

    Article  PubMed  CAS  Google Scholar 

  34. 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  PubMed  CAS  Google Scholar 

  35. Isolauri J, Luostarinen M, Isolauri E, et al.: Natural course of gastroesophageal reflux disease: 17–22 year follow-up of 60 patients. Am J Gastroenterol 1997, 92:37–41.

    PubMed  CAS  Google Scholar 

  36. McDougall N, Johnston B, Kee F, et al.: Natural history of reflux oesophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life. Gut 1996, 38:481–486.

    Article  PubMed  CAS  Google Scholar 

  37. McDougall N, Johnston B, Collins J, et al.: 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, 9:1161–1167.

    PubMed  CAS  Google Scholar 

  38. Manabe N, Yoshihara M, Sasaki A, et al.: Clinical characteristics and natural history of patients with low-grade reflux esophagitis. J Gastroenterol Hepatol 2002, 17:949–954.

    Article  PubMed  Google Scholar 

  39. Labenz J, Nocon M, Lind T, et al.: Prospective follow-up data from the ProGERD study suggest that GERD is not a categorical disease. Am J Gastroenterol 2006, 101:2457–2462.

    PubMed  Google Scholar 

  40. Willich S, Nocon M, Kulig M, et al.: Cost-of-disease analysis in patients with gastro-oesophageal reflux disease and Barrett’s mucosa. Aliment Pharmacol Ther 2006, 23:371–376.

    Article  PubMed  CAS  Google Scholar 

  41. Garrido Serrano A, Guerrero Igea FJ, Lepe Jiménez JA, Perianes Hernández C: Clinical features and endoscopic progression of gastroesophageal reflux disease. Rev Esp Enferm Dig 2003, 95:712–716.

    PubMed  CAS  Google Scholar 

  42. Sontag S, Sonnenberg A, Schnell T, et al.: The long-term natural history of gastroesophageal reflux disease. J Clin Gastroenterol 2006, 40:398–404.

    Article  PubMed  Google Scholar 

  43. Bardhan KD, Royston C, Nayyar AK: Reflux rising! An essay on witnessing a disease in evolution. Dig Liver Dis 2006, 38:163–168

    Article  PubMed  CAS  Google Scholar 

  44. Cameron A, Lagergren J, Henriksson C, et al.: Gastroesophageal reflux disease in monozygotic and dizygotic twins. Gastroenterology 2002, 122:55–59.

    Article  PubMed  Google Scholar 

  45. Romero Y, Cameron A, Locke G, 3rd, et al.: Familial aggregation of gastroesophageal reflux in patients with Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology 1997, 113:1449–1456.

    Article  PubMed  CAS  Google Scholar 

  46. Quigley E: Factors that influence therapeutic outcomes in symptomatic gastroesophageal reflux disease. Am J Gastroenterol 2003, 98(3 Suppl):S24–S30.

    Article  PubMed  Google Scholar 

  47. Castell D, Kahrilas P, Richter J, et al.: Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol 2002, 97:575–583.

    Article  PubMed  CAS  Google Scholar 

  48. Hetzel D, Dent J, Reed W, et al.: Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology 1988, 95:903–912.

    PubMed  CAS  Google Scholar 

  49. Sifrim D, Holloway R, Silny J, et al.: Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings. Gastroenterology 2001, 120:1588–1598.

    Article  PubMed  CAS  Google Scholar 

  50. Fass R, Naliboff B, Higa L, et al.: Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. Gastroenterology 1988, 115:1363–1373.

    Article  Google Scholar 

  51. Vela M, Camacho-Lobato L, Srinivasan R, et al.: Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole. Gastroenterology 2001, 120:1599–1606.

    Article  PubMed  CAS  Google Scholar 

  52. Wiklund I, Bardhan K, Muller-Lissner S, et al.: Quality of life during acute and intermittent treatment of gastrooesophageal 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.

    PubMed  CAS  Google Scholar 

  53. Stalhammer N, Carlsson J, Peacock R, et al.: Cost effectiveness of omeprazole and ranitidine in intermittent treatment of symptomatic gastro-oesophageal reflux disease. Pharmacoeconomics 1999, 16:483–497.

    Article  Google Scholar 

  54. Gerson L, Robbins A, Garbert A, et al.: A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease. Gastroenterology 2000, 95:395–407.

    Article  CAS  Google Scholar 

  55. Galmiche JP, Barthelemy P, Hamelin B: Treating the symptoms of gastro-oesophageal reflux disease: a double-blind comparison of omeprazole and cisapride. Aliment Pharmacol Ther 1997, 11:765–773.

    Article  PubMed  CAS  Google Scholar 

  56. Dean B, Gano A, Jr, Knight K, et al.: Effectiveness of proton pump inhibitors in nonerosive reflux disease. Clin Gastroenterol Hepatol 2004, 2:656–664.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. GI Section (1-111G-1), The Neuro-Enteric Clinical Research Group, Southern Arizona VA Health Care System, 3601 South 6th Avenue, Tucson, AZ, 85723-0001, USA

    Ronnie Fass

Authors
  1. Tomás Navarro-Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronnie Fass
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronnie Fass.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navarro-Rodriguez, T., Fass, R. Functional heartburn, nonerosive reflux disease, and reflux esophagitis are all distinct conditions—A debate: Pro. Curr GERD Rep 1, 259–266 (2007). https://doi.org/10.1007/s12171-007-0026-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12171-007-0026-9

Keywords

Search

Navigation