Skip to main content

Advertisement

Log in

Extra-Esophageal Manifestations of Gerd: Who Responds to GERD Therapy?

  • Esophagus (L Gerson, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Gastroesophageal reflux disease (GERD) is a common disease that is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms. In addition to the esophageal manifestations of heartburn and regurgitation, the role of GERD in causing extra-esophageal symptoms, such as laryngitis, asthma, cough, chest pain, and dental erosions, is increasingly recognized with renewed interest. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPI) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. In those who are unresponsive to such therapy, other diagnostic testing such as impedance/pH monitoring may be reasonable in order to exclude continued acid or weakly acid reflux. Recent data suggest that patients with extra-esophageal symptoms who have concomitant typical symptoms, moderate-sized hiatal hernia and moderate reflux on pH testing may respond better to acid suppressive therapy. This group only accounts for 20−30 % of patients commonly referred for suspected GERD. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal signs and symptoms and continued PPI therapy in this group is not recommended.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Spechler SJ. Epidemiology and natural history of gastro-oesophageal reflux disease. Digestion. 1992;51 Suppl 1:24–9.

    Article  PubMed  Google Scholar 

  2. Vaezi MF. Therapy Insight: gastroesophageal reflux disease and laryngopharyngeal reflux. Nat Clin Pract Gastroenterol Hepatol. 2005;2:595–603.

    Article  PubMed  Google Scholar 

  3. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–20. quiz 43.

    Article  PubMed  Google Scholar 

  4. Rodriguez-Tellez M. Supra-oesophageal manifestations of gastro-oesophageal reflux disease. Drugs. 2005;65 Suppl 1:67–73.

    PubMed  Google Scholar 

  5. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991;101:1–78.

    Article  PubMed  CAS  Google Scholar 

  6. Field SK, Underwood M, Brant R, Cowie RL. Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996;109:316–22.

    Article  PubMed  CAS  Google Scholar 

  7. Groen JN, Smout AJ. Supra-oesophageal manifestations of gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2003;15:1339–50.

    Article  PubMed  Google Scholar 

  8. Yuksel ES, Vaezi MF. Extraesophageal manifestations of gastroesophageal reflux disease: cough, asthma, laryngitis, chest pain. Swiss Med Wkly. 2012;142:w13544.

    Google Scholar 

  9. Stanghellini V. Relationship between upper gastrointestinal symptoms and lifestyle, psychosocial factors and comorbidity in the general population: results from the Domestic/International Gastroenterology Surveillance Study (DIGEST). Scand J Gastroenterol Suppl. 1999;231:29–37.

    PubMed  CAS  Google Scholar 

  10. Poe RH, Kallay MC. Chronic cough and gastroesophageal reflux disease: experience with specific therapy for diagnosis and treatment. Chest. 2003;123:679–84.

    Article  PubMed  Google Scholar 

  11. • Roberts JR, Aravapalli A, Pohl D, et al. Extraesophageal gastroesophageal reflux disease (GERD) symptoms are not more frequently associated with proximal esophageal reflux than typical GERD symptoms. Dis Esophagus. 2012;25(8):678–81. Prospective review comparing the differences in proximal reflux in esophageal versus extraesophageal symptoms.

    Article  PubMed  CAS  Google Scholar 

  12. • Aslam M, Slaughter JC, Goutte M, et al. Nonlinear relationship between body mass index and esophageal acid exposure in the extraesophageal manifestations of reflux. Clin Gastroenterol Hepatol. 2012;10(8):874–8. This study describes the relationship of obesity with GERD for physician guidance on weight goals.

    Article  PubMed  Google Scholar 

  13. Abou-Ismail A, Vaezi MF. Evaluation of patients with suspected laryngopharyngeal reflux: a practical approach. Curr Gastroenterol Rep. 2011;13(3):213–8.

    Article  PubMed  Google Scholar 

  14. Adhami T, Goldblum JR, Richter JE, Vaezi MF. The role of gastric and duodenal agents in laryngeal injury: an experimental canine model. Am J Gastroenterol. 2004;99:2098–106.

    Article  PubMed  Google Scholar 

  15. • Bardhan KD, Strugala V, Dettmar PW. Reflux revisited: advancing the role of pepsin. Int J Otolaryngol. 2012;2012:646901. This article discusses the newest review of pepsin along with its potential detection for treatment of GERD that is not responsive to GERD.

    PubMed  Google Scholar 

  16. Richter JE. Typical and atypical presentations of gastroesophageal reflux disease. The role of esophageal testing in diagnosis and management. Gastroenterol Clin North Am. 1996;25:75–102.

    Article  PubMed  CAS  Google Scholar 

  17. Ahmed T, Vaezi MF. The role of pH monitoring in extraesophageal reflux. Gastrointestinal Endosc Clin N Am. 2005;15:319–31.

    Article  Google Scholar 

  18. Vaezi MF, Schroeder PL, Richter JE. Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring. Am J Gastroenterol. 1997;92:825–9.

    PubMed  CAS  Google Scholar 

  19. Joniau S, Bradshaw A, Esterman A, Carney AS. Reflux and laryngitis: a systematic review. Otolaryngol Head Neck Surg. 2007;136(5):686–92.

    Article  PubMed  Google Scholar 

  20. Noordzij JP, Khidr A, Desper E, et al. Correlation of pH probe-measured laryngopharyngeal reflux with symptoms and signs of reflux laryngitis. Laryngoscope. 2002;112(12):2192–5.

    Article  PubMed  Google Scholar 

  21. 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;55:1398–402.

    Article  PubMed  CAS  Google Scholar 

  22. Mainie I, Tutuian R, Agrawal A, et al. Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication. Br J Surg. 2006;93:1483–7.

    Article  PubMed  CAS  Google Scholar 

  23. Vaezi MF. Laryngitis and gastroesophageal reflux disease: increasing prevalence or poor diagnostic tests? Am J Gastroenterol. 2004;99(5):786–8.

    Article  PubMed  Google Scholar 

  24. •• Francis DO, Goutte M, Slaughter JC, et al. Traditional reflux parameters and not impedance monitoring predict outcome after fundoplication in extraesophageal reflux. Laryngoscope. 2011;121(9):1902–9. The most recent uncontrolled surgical study in patients suspected of having LPR.

    PubMed  Google Scholar 

  25. Vavricka SR, Storck CA, Wildi SM, et al. Limited diagnostic value of laryngopharyngeal lesions in patients with gastroesophageal reflux during routine upper gastrointestinal endoscopy. Am J Gastroenterol. 2007;102(4):716–22.

    Article  PubMed  Google Scholar 

  26. Milstein CF, Charbel S, Hicks DM, et al. Prevalence of laryngeal irritation signs associated with reflux in asymptomatic volunteers: impact of endoscopic technique (rigid vs. flexible laryngoscope). Laryngoscope. 2005;115(12):2256–61.

    Article  PubMed  Google Scholar 

  27. • Yuksel ES, Slaughter JC, Mucktar N, et al. In vitro and in vivo studies with a novel oropharyngeal ph monitoring device implicates utility in chronic laryngitis. Neurogastroenterol Motil. 2013. in review. A comparison of oropharyngeal pH monitoring to the traditional pH catheters.

  28. Sun G, Muddana S, Slaughter JC, et al. A new pH catheter for laryngopharyngeal reflux: normal values. Laryngoscope. 2009;119:1639–43.

    Article  PubMed  Google Scholar 

  29. Wiener GJ, Tsukashima R, Kelly C, et al. Oropharyngeal pH monitoring for the detection of liquid and aerosolized supraesophageal gastric reflux. J Voice. 2009;23:498–504.

    Article  PubMed  Google Scholar 

  30. Potluri S, Friedenberg F, Parkman HP, et al. Comparison of a salivary/sputum pepsin assay with 24-hour esophageal pH monitoring for detection of gastric reflux into the proximal esophagus, oropharynx, and lung. Dig Dis Sci. 2003;48:1813–7.

    Article  PubMed  CAS  Google Scholar 

  31. Ozmen S, Yucel OT, Sinici I, et al. Nasal pepsin assay and pH monitoring in chronic rhinosinusitis. Laryngoscope. 2008;118:890–4.

    Article  PubMed  Google Scholar 

  32. Printza A, Speletas M, Triaridis S, et al. Is pepsin detected in the saliva of patients who experience pharyngeal reflux? Hippokratia. 2007;11:145–9.

    PubMed  CAS  Google Scholar 

  33. Kim TH, Lee KJ, Yeo M, et al. Pepsin detection in the sputum/saliva for the diagnosis of gastroesophageal reflux disease in patients with clinically suspected atypical gastroesophageal reflux disease symptoms. Digestion. 2008;77:201–6.

    Article  PubMed  CAS  Google Scholar 

  34. • Yuksel ES, Hong SK, Strugala V, et al. Rapid salivary pepsin test: blinded assessment of test performance in GERD. Laryngoscope. 2013;122:1312–6. Recently conducted prospective, blinded study of salivary pepsin assay in 59 patients with objective GERD.

    Article  Google Scholar 

  35. Park W, Hicks DM, Khandwala F, et al. Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope. 2005;115:1230–8.

    Article  PubMed  CAS  Google Scholar 

  36. Williams RB, Szczesniak MM, Maclean JC, et al. Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis. Am J Gastroenterol. 2004;99:777–85.

    Article  PubMed  CAS  Google Scholar 

  37. Vaezi MF, Richter JE, Stasney CR, et al. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope. 2006;116:254–60.

    Article  PubMed  CAS  Google Scholar 

  38. Qadeer MA, Phillips CO, Lopez AR, et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006;101:2646–54.

    Article  PubMed  CAS  Google Scholar 

  39. Swoger J, Ponsky J, Hicks DM, et al. Surgical fundoplication in laryngopharyngeal reflux unresponsive to aggressive acid suppression: a controlled study. Clin Gastroenterol Hepatol. 2006;4(4):433–41.

    Article  PubMed  Google Scholar 

  40. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis. 1981;123:413–7.

    PubMed  CAS  Google Scholar 

  41. Irwin RS, Zawacki JK, Curley FJ, et al. Chronic cough as the sole presenting manifestation of gastroesophageal reflux. Am Rev Respir Dis. 1989;140:1294–300.

    Article  PubMed  CAS  Google Scholar 

  42. Harding SM, Richter JE. The role of gastroesophageal reflux in chronic cough and asthma. Chest. 1997;111:1389–402.

    Article  PubMed  CAS  Google Scholar 

  43. Baldi F, Cappiello R, Cavoli C, et al. Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough: a comparison between two different daily doses of lansoprazole. World J Gastroenterol. 2006;12(1):82–8.

    PubMed  CAS  Google Scholar 

  44. Chandra KM, Harding SM. Therapy insight: treatment of gastroesophageal reflux in adults with chronic cough. Nat Clin Pract Gastroenterol Hepatol. 2007;4(11):604–13.

    Article  PubMed  Google Scholar 

  45. McGarvey LP, Heaney LG, Lawson JT, et al. Evaluation and outcome of patients with chronic nonproductive cough using a comprehensive diagnostic protocol. Thorax. 1998;53(9):738–43.

    Article  PubMed  CAS  Google Scholar 

  46. 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;10:868–74.

    Article  Google Scholar 

  47. • Kavitt RT, Higginbotham T, Slaughter JC, et al. Symptom reports are not reliable during ambulatory reflux monitoring. Am J Gastroenterol. 2012;107(12):1826–32. Recent data correlating concomitant impedance-pH and acoustic cough monitoring.

    Article  PubMed  Google Scholar 

  48. Ours TM, Kavuru MS, Schilz RJ, Richter JE. A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol. 1999;94(11):3131–8.

    Article  PubMed  CAS  Google Scholar 

  49. Chang AB, Lasserson TJ, Gaffney J, et al. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev 2005;CD004823.

  50. • Faruqi S, Molyneux ID, Fathi H, et al. Chronic cough and esomeprazole: a double-blind placebo-controlled parallel study. Respirology. 2011;16:1150–6. A recent prospective, single-center, randomized, double-blind, placebo-controlled, parallel group study conducted over 8 weeks examining adult non-smokers with chronic cough and normal spirometry.

    Article  PubMed  Google Scholar 

  51. • Shaheen NJ, Crockett SD, Bright SD, et al. Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33:225–34. Clinical trial examining the impact of high-dose acid suppression with proton pump inhibitors on chronic cough in subjects with rare or no heartburn.

    Article  PubMed  CAS  Google Scholar 

  52. Mays EE. Intrinsic asthma in adults. Association with gastroesophageal reflux. JAMA. 1976;236:2626–8.

    Article  PubMed  CAS  Google Scholar 

  53. Sontag SJ. The spectrum of pulmonary symptoms due to gastroesophageal reflux. Thorac Surg Clin. 2005;15:353–68.

    Article  PubMed  Google Scholar 

  54. Simpson WG. Gastroesophageal reflux disease and asthma. Diagnosis and management. Arch Intern Med. 1995;155:798–803.

    Article  PubMed  CAS  Google Scholar 

  55. Leggett JJ, Johnston BT, Mills M, et al. Prevalence of gastroesophageal reflux in difficult asthma: relationship to asthma outcome. Chest. 2005;127(4):1227–31.

    Article  PubMed  Google Scholar 

  56. Havemann BD, Henderson CA, El-Serag HB. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. 2007;56:1654–64.

    Article  PubMed  CAS  Google Scholar 

  57. Kiljander TO, Salomaa ER, Hietanen EK, et al. Gastroesophageal reflux in asthmatics: a double-blind, placebo-controlled crossover study with omeprazole. Chest. 1999;116:1257–64.

    Article  PubMed  CAS  Google Scholar 

  58. Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996;100:395–405.

    Article  PubMed  CAS  Google Scholar 

  59. Littner MR, Leung FW, Ballard ED, et al. Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms. Chest. 2005;128:1128–35.

    Article  PubMed  CAS  Google Scholar 

  60. Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2006;173(10):1091–7.

    Article  PubMed  CAS  Google Scholar 

  61. Sontag SJ, O’Connell S, Khandelwal S, et al. Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol. 2003;98(5):987–99.

    PubMed  Google Scholar 

  62. Mastronarde JG, Anthonisen NR, Castro M, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360(15):1487–99.

    Article  PubMed  CAS  Google Scholar 

  63. Gibson PG, Powell H, Coughlan J, et al. Limited (information only) patient education programs for adults with asthma. Cochrane Database Syst Rev. 2002;2:CD001005.

    PubMed  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael F. Vaezi.

Additional information

This article is part of the Topical Collection on Esophagus

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naik, R.D., Vaezi, M.F. Extra-Esophageal Manifestations of Gerd: Who Responds to GERD Therapy?. Curr Gastroenterol Rep 15, 318 (2013). https://doi.org/10.1007/s11894-013-0318-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-013-0318-4

Keywords

Navigation