Skip to main content
Log in

Reflux and Voice Disorders: Have We Established Causality?

  • Professional Voice Disorders (G Garrett, Section Editor)
  • Published:
Current Otorhinolaryngology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

A trend of attributing abnormal voice changes to reflux has gained momentum among medical professionals over the last few decades. Evidence supporting the connection between reflux and voice and the use of anti-reflux medication in patients with dysphonia is conflicting and deserves careful examination. In the current health care environment, it is important that medical decisions be based on science rather than anecdote and practice patterns. The goal of this review is to investigate the evidence linking reflux and voice changes. Specifically, this association will be examined in the context of the Bradford Hill criteria to determine what evidence exists for a causal relationship between this exposure (reflux) and outcome (voice change).

Summary

Using the Bradford Hill criteria as a rubric, the evidence toward causality between reflux and voice is insufficient. The most compelling data derived from animal studies show biological plausibility, since an acidic environment does induce mucosal changes. However, evidence from human studies is largely associative. To date, neither clinical trials nor comparative observational studies have been able to demonstrate a strong dose–response relationship between reflux and voice disorders, temporality (reflux precedes dysphonia), consistent treatment effects, or strength of association between anti-reflux treatment and improved voice among patients with presumed laryngopharyngeal reflux (LPR). Nonetheless, a relationship does exist between LPR and voice and it deserves careful consideration. However, the strength and nature of that association remain unclear.

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.

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. Popper KR. The logic of scientific discovery. London: Hutchinson; 1972.

    Google Scholar 

  2. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Hoppo T, Sanz AF, Nason KS, et al. How much pharyngeal exposure is “normal”? Normative data for laryngopharyngeal reflux events using hypopharyngeal multichannel intraluminal impedance (HMII). J Gastrointest Surg. 2012;16:16–24 discussion 24–5.

    Article  PubMed  Google Scholar 

  4. Wood JM, Hussey DJ, Woods CM, et al. Biomarkers and laryngopharyngeal reflux. J Laryngol Otol. 2011;125:1218–24.

    Article  CAS  PubMed  Google Scholar 

  5. Crapko M, Kerschner JE, Syring M, et al. Role of extra-esophageal reflux in chronic otitis media with effusion. Laryngoscope. 2007;117:1419–23.

    Article  PubMed  Google Scholar 

  6. Johnston N, Wells CW, Blumin JH, et al. Receptor-mediated uptake of pepsin by laryngeal epithelial cells. Ann Otol Rhinol Laryngol. 2007;116:934–8.

    Article  PubMed  Google Scholar 

  7. Koufman JA. Low-acid diet for recalcitrant laryngopharyngeal reflux: therapeutic benefits and their implications. Ann Otol Rhinol Laryngol. 2011;120:281–7.

    Article  PubMed  Google Scholar 

  8. Johnston N, Bulmer D, Gill GA, et al. Cell biology of laryngeal epithelial defenses in health and disease: further studies. Ann Otol Rhinol Laryngol. 2003;112:481–91.

    Article  PubMed  Google Scholar 

  9. Johnston N, Knight J, Dettmar PW, et al. Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope. 2004;114:2129–34.

    Article  CAS  PubMed  Google Scholar 

  10. Altman KW, Kinoshita Y, Tan M, et al. Western blot confirmation of the H+/K+-ATPase proton pump in the human larynx and submandibular gland. Otolaryngol Head Neck Surg. 2011;145:783–8.

    Article  PubMed  Google Scholar 

  11. Altman KW, Haines GK 3rd, Hammer ND, et al. The H+/K+-ATPase (proton) pump is expressed in human laryngeal submucosal glands. Laryngoscope. 2003;113:1927–30.

    Article  CAS  PubMed  Google Scholar 

  12. Becker V, Drabner R, Graf S, et al. New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal pH metry in extraesophageal gastroesophageal reflux disease. World J Gastroenterol. 2015;21:982–7.

    PubMed  PubMed Central  Google Scholar 

  13. Adhami T, Goldblum JR, Richter JE, et al. 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 

  14. Delahunty JE, Cherry J. Experimentally produced vocal cord granulomas. Laryngoscope. 1968;78:1941–7.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    CAS  PubMed  Google Scholar 

  16. Merati AL, Lim HJ, Ulualp SO, et al. Meta-analysis of upper probe measurements in normal subjects and patients with laryngopharyngeal reflux. Ann Otol Rhinol Laryngol. 2005;114:177–82.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  18. •• Ruiz R, Jeswani S, Andrews K, et al. Hoarseness and laryngopharyngeal reflux: a survey of primary care physician practice patterns. JAMA Otolaryngol Head Neck Surg. 2014;140:192–6. An interesting survey study demonstrating how LPR has become a common diagnosis in primary care offices for persistent dysphonia.

  19. Koufman JA, Aviv JE, Casiano RR, et al. Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngol Head Neck Surg. 2002;127:32–5.

    Article  PubMed  Google Scholar 

  20. • Ates F, Yuksel ES, Higginbotham T, et al. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology. 2015;148:334–43. The article describes the potential role for mucosal impedance in the diagnosis of LPR.

  21. Fass R, Noelck N, Willis MR, et al. The effect of esomeprazole 20 mg twice daily on acoustic and perception parameters of the voice in laryngopharyngeal reflux. Neurogastroenterol Motil. 2010;22(134–41):e44–5.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. El-Serag HB, Lee P, Buchner A, et al. Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial. Am J Gastroenterol. 2001;96:979–83.

    Article  CAS  PubMed  Google Scholar 

  24. Noordzij JP, Khidr A, Evans BA, et al. Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study. Laryngoscope. 2001;111:2147–51.

    Article  CAS  PubMed  Google Scholar 

  25. Eherer AJ, Habermann W, Hammer HF, et al. Effect of pantoprazole on the course of reflux-associated laryngitis: a placebo-controlled double-blind crossover study. Scand J Gastroenterol. 2003;38:462–7.

    Article  CAS  PubMed  Google Scholar 

  26. Wo JM, Koopman J, Harrell SP, et al. Double-blind, placebo-controlled trial with single-dose pantoprazole for laryngopharyngeal reflux. Am J Gastroenterol. 2006;101:1972–8 quiz 2169.

    Article  CAS  PubMed  Google Scholar 

  27. Reichel O, Dressel H, Wiederanders K, et al. Double-blind, placebo-controlled trial with esomeprazole for symptoms and signs associated with laryngopharyngeal reflux. Otolaryngol Head Neck Surg. 2008;139:414–20.

    Article  PubMed  Google Scholar 

  28. Havas T, Huang S, Levy M, et al. Posterior pharyngolaryngitis: double-blind randomised placebo-controlled trial of proton pump inhibitor therapy. Aust J Otolaryngol. 1999;3:243.

    Google Scholar 

  29. Steward DL, Wilson KM, Kelly DH, et al. Proton pump inhibitor therapy for chronic laryngo-pharyngitis: a randomized placebo-control trial. Otolaryngol Head Neck Surg. 2004;131:342–50.

    Article  PubMed  Google Scholar 

  30. •• Park JO, Shim MR, Hwang YS, et al. Combination of voice therapy and antireflux therapy rapidly recovers voice-related symptoms in laryngopharyngeal reflux patients. Otolaryngol Head Neck Surg. 2012;146:92–7. An important study to consider, especially for patients who have failed initial LPR treatment. As well it suggests that many patients diagnosed with LPR may have a functional cause for their dysphonia.

  31. da Costa BR, Rutjes AW, Johnston BC, et al. Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta-epidemiological study. Int J Epidemiol. 2012;41:1445–59.

    Article  PubMed  Google Scholar 

  32. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope. 2001;111:1313–7.

    Article  CAS  PubMed  Google Scholar 

  33. Powell J, Cocks HC. Mucosal changes in laryngopharyngeal reflux–prevalence, sensitivity, specificity and assessment. Laryngoscope. 2013;123:985–91.

    Article  PubMed  Google Scholar 

  34. Oelschlager BK, Eubanks TR, Maronian N, et al. Laryngoscopy and pharyngeal pH are complementary in the diagnosis of gastroesophageal–laryngeal reflux. J Gastrointest Surg. 2002;6:189–94.

    Article  PubMed  Google Scholar 

  35. • Chang BA, MacNeil SD, Morrison MD, et al. The reliability of the reflux finding score among general otolaryngologists. J Voice. 2015;29:572–7. An important study to consider when evaluating other trials whose inclusion criteria and/or treatment response relies upon the RFS.

  36. Branski RC, Bhattacharyya N, Shapiro J. The reliability of the assessment of endoscopic laryngeal findings associated with laryngopharyngeal reflux disease. Laryngoscope. 2002;112:1019–24.

    Article  PubMed  Google Scholar 

  37. Kelchner LN, Horne J, Lee L, et al. Reliability of speech-language pathologist and otolaryngologist ratings of laryngeal signs of reflux in an asymptomatic population using the reflux finding score. J Voice. 2007;21:92–100.

    Article  PubMed  Google Scholar 

  38. Musser J, Kelchner L, Neils-Strunjas J, et al. A comparison of rating scales used in the diagnosis of extraesophageal reflux. J Voice. 2011;25:293–300.

    Article  PubMed  Google Scholar 

  39. Eren E, Arslanoglu S, Aktas A, et al. Factors confusing the diagnosis of laryngopharyngeal reflux: the role of allergic rhinitis and inter-rater variability of laryngeal findings. Eur Arch Otorhinolaryngol. 2014;271:743–7.

    Article  PubMed  Google Scholar 

  40. Mesallam TA, Stemple JC, Sobeih TM, et al. Reflux symptom index versus reflux finding score. Ann Otol Rhinol Laryngol. 2007;116:436–40.

    Article  PubMed  Google Scholar 

  41. Park KH, Choi SM, Kwon SU, et al. Diagnosis of laryngopharyngeal reflux among globus patients. Otolaryngol Head Neck Surg. 2006;134:81–5.

    Article  PubMed  Google Scholar 

  42. Hicks DM, Ours TM, Abelson TI, et al. The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice. 2002;16:564–79.

    Article  PubMed  Google Scholar 

  43. 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;115:2256–61.

    Article  PubMed  Google Scholar 

  44. Lundy DS, Casiano RR, Sullivan PA, et al. Incidence of abnormal laryngeal findings in asymptomatic singing students. Otolaryngol Head Neck Surg. 1999;121:69–77.

    Article  CAS  PubMed  Google Scholar 

  45. •• 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. This article comes from the GI literature and concludes that laryngoscopy alone is not a reliable diagnostic tool for LPR. This conclusion and treatment guideline oppose those in the ENT literature.

  46. Ylitalo R, Ramel S. Extraesophageal reflux in patients with contact granuloma: a prospective controlled study. Ann Otol Rhinol Laryngol. 2002;111:441–6.

    Article  PubMed  Google Scholar 

  47. Karkos PD, George M, Van Der Veen J, et al. Vocal process granulomas: a systematic review of treatment. Ann Otol Rhinol Laryngol. 2014;123:314–20.

    Article  PubMed  Google Scholar 

  48. Wang CP, Ko JY, Wang YH, et al. Vocal process granuloma—a result of long-term observation in 53 patients. Oral Oncol. 2009;45:821–5.

    Article  PubMed  Google Scholar 

  49. Francis DO, Sharda R, Patel DA, et al. Developmental characteristics of patient-reported outcome measures related to laryngopharyngeal reflux: a systematic review. 2016 (under review).

  50. Guyatt GH, Osoba D, Wu AW, et al. Methods to explain the clinical significance of health status measures. Mayo Clin Proc. 2002;77:371–83.

    Article  PubMed  Google Scholar 

  51. • Patel AK, Mildenhall NR, Kim W, et al. Symptom overlap between laryngopharyngeal reflux and glottic insufficiency in vocal fold atrophy patients. Ann Otol Rhinol Laryngol. 2014;123:265–70. This article demonstrates that other laryngeal disorders can mimic the clinical presentation of LPR. This is particularly important given that many PCPs are treatment with PPI prior to laryngoscopic evaluation by an ENT.

  52. Rafii B, Taliercio S, Achlatis S, et al. Incidence of underlying laryngeal pathology in patients initially diagnosed with laryngopharyngeal reflux. Laryngoscope. 2014;124:1420–4.

    Article  PubMed  Google Scholar 

  53. 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  CAS  PubMed  Google Scholar 

  54. Sulica L. Hoarseness misattributed to reflux: sources and patterns of error. Ann Otol Rhinol Laryngol. 2014;123:442–5.

    Article  PubMed  Google Scholar 

  55. Qadeer MA, Lopez R, Wood BG, et al. Does acid suppressive therapy reduce the risk of laryngeal cancer recurrence? Laryngoscope. 2005;115:1877–81.

    Article  PubMed  Google Scholar 

  56. 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  CAS  PubMed  Google Scholar 

  57. Guo H, Ma H, Wang J. Proton pump inhibitor therapy for the treatment of laryngopharyngeal reflux: a meta-analysis of randomized controlled trials. J Clin Gastroenterol. 2016;50:295–300.

    Article  CAS  PubMed  Google Scholar 

  58. Lindstrom DR, Wallace J, Loehrl TA, et al. Nissen fundoplication surgery for extraesophageal manifestations of gastroesophageal reflux (EER). Laryngoscope. 2002;112:1762–5.

    Article  CAS  PubMed  Google Scholar 

  59. Westcott CJ, Hopkins MB, Bach K, et al. Fundoplication for laryngopharyngeal reflux disease. J Am Coll Surg. 2004;199:23–30.

    Article  PubMed  Google Scholar 

  60. Ogut F, Ersin S, Engin EZ, et al. The effect of laparoscopic Nissen fundoplication on laryngeal findings and voice quality. Surg Endosc. 2007;21:549–54.

    Article  CAS  PubMed  Google Scholar 

  61. Sahin M, Vardar R, Ersin S, et al. The effect of antireflux surgery on laryngeal symptoms, findings and voice parameters. Eur Arch Otorhinolaryngol. 2015;272:3375–83.

    Article  PubMed  Google Scholar 

  62. Catania RA, Kavic SM, Roth JS, et al. Laparoscopic Nissen fundoplication effectively relieves symptoms in patients with laryngopharyngeal reflux. J Gastrointest Surg. 2007;11:1579–87 discussion 1587–8.

    Article  PubMed  Google Scholar 

  63. Sala E, Salminen P, Simberg S, et al. Laryngopharyngeal reflux disease treated with laparoscopic fundoplication. Dig Dis Sci. 2008;53:2397–404.

    Article  PubMed  Google Scholar 

  64. Wassenaar E, Johnston N, Merati A, et al. Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication. Surg Endosc. 2011;25:3870–6.

    Article  PubMed  Google Scholar 

  65. van der Westhuizen L, Von SJ, Wilkerson BJ, et al. Impact of Nissen fundoplication on laryngopharyngeal reflux symptoms. Am Surg. 2011;77:878–82.

    PubMed  Google Scholar 

  66. Trad KS, Turgeon DG, Deljkich E. Long-term outcomes after transoral incisionless fundoplication in patients with GERD and LPR symptoms. Surg Endosc. 2012;26:650–60.

    Article  PubMed  Google Scholar 

  67. Weber B, Portnoy JE, Castellanos A, et al. Efficacy of anti-reflux surgery on refractory laryngopharyngeal reflux disease in professional voice users: a pilot study. J Voice. 2014;28:492–500.

    Article  PubMed  Google Scholar 

  68. Hamdy E, El Nakeeb A, Hamed H, et al. Outcome of laparoscopic Nissen fundoplication for gastroesophageal reflux disease in non-responders to proton pump inhibitors. J Gastrointest Surg. 2014;18:1557–62.

    Article  PubMed  Google Scholar 

  69. Hamdy E, El-Shahawy M, Abd El-Shoubary M, et al. Response of atypical symptoms of GERD to antireflux surgery. Hepatogastroenterology. 2009;56:403–6.

    CAS  PubMed  Google Scholar 

  70. 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;4:433–41.

    Article  PubMed  Google Scholar 

  71. Francis DO, Goutte M, Slaughter JC, et al. Traditional reflux parameters and not impedance monitoring predict outcome after fundoplication in extraesophageal reflux. Laryngoscope. 2011;121:1902–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David O. Francis.

Ethics declarations

Conflict of Interest

G. Todd Schneider, Michael F. Vaezi, and David O. Francis declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Professional Voice Disorders.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Todd Schneider, G., Vaezi, M.F. & Francis, D.O. Reflux and Voice Disorders: Have We Established Causality?. Curr Otorhinolaryngol Rep 4, 157–167 (2016). https://doi.org/10.1007/s40136-016-0121-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40136-016-0121-5

Keywords

Navigation