Gastric pepsin in middle ear fluid of children with otitis media: Clinical implications


Gastroesophageal reflux and extraesophageal reflux have been postulated to be involved in the pathogenesis of otitis media. This is supported by recent studies revealing the presence of gastric pepsin in the middle ear space of children with otitis media but not in control patients without otitis media. Reflux’s role in otitis media appears to be most pronounced in younger children and those with purulent effusions.

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References and Recommended Reading

  1. 1.

    Lubianca Neto JF, Hemb L, Silva DB: Systematic review of modifiable risk factors for recurrent acute otitis media in childhood. J Pediatr (Rio J) 2006, 82:87–96.

    Article  Google Scholar 

  2. 2.

    Hing E, Middleton K: National hospital ambulatory medical care survey: 2001 outpatient department survey. Adv Data 2003, 338:1–26.

    PubMed  Google Scholar 

  3. 3.

    Berman S, Byrns PJ, Bondy J, et al.: Otitis media-related antibiotic prescribing patterns, outcomes, and expenditures in a pediatric Medicaid population. Pediatrics 1997, 100:585–592.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Bluestone CD: Studies in otitis media: Children’s Hospital of Pittsburgh-University of Pittsburgh Progress Report-2004. Laryngoscope 2004, 114(Suppl 105):1–26.

    PubMed  Article  Google Scholar 

  5. 5.

    Rosenfeld RM, Culpepper L, Doyle KJ, et al.: Clinical practice guideline: otitis media with effusion. Otolaryngol Head Neck Surg 2004, 130(Suppl 5):S95–S118.

    PubMed  Article  Google Scholar 

  6. 6.

    Nelson SP, Chen EH, Syniar GM, Christoffel KK: Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 1997, 151:569–572.

    PubMed  CAS  Google Scholar 

  7. 7.

    Gibson WS, Cochran W: Otalgia in infants and children: a manifestation of gastroesophageal reflux. Int J Pediatr Otorhinolaryngol 1994, 28:213–218.

    PubMed  Article  Google Scholar 

  8. 8.

    Poelmans J, Tack J, Feenstra L: Prospective study on the incidence of chronic ear complaints related to gastroesophageal reflux and on the outcome of antireflux therapy. Ann Otol Rhinol Laryngol 2002, 111:933–938.

    PubMed  Google Scholar 

  9. 9.

    McGuirt WF: Gastroesophageal reflux and the upper airway. Pediatr Clin North Am 2003, 50:487–502.

    PubMed  Article  Google Scholar 

  10. 10.

    Burton DM, Pransky SM, Katz RM, et al.: Pediatric airway manifestations of gastroesophageal reflux disease. Ann Otol Rhinol Laryngol 1992, 101:742–749.

    PubMed  CAS  Google Scholar 

  11. 11.

    O’Reilly RC, He Z, Bloedon E, et al.: The role of extraesophageal reflux in otitis media in infants and children. Laryngoscope 2008, 118(Suppl 116):1–9.

    PubMed  Article  Google Scholar 

  12. 12.

    Cusimano F, Cocita VC, D’Amico A: Sensorineural hearing loss in chronic otitis media. J Laryngol Otol 1989, 103:158–163.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Bluestone CD, Klein JO: Otitis media and eustachian tube dysfunction. In Pediatric Otolaryngology. Edited by Bluestone CD, Stool SE, Alper SM, et al. Philadelphia: Saunders; 2003:474–685.

    Google Scholar 

  14. 14.

    Heavner SB, Hardy SM, White DR, et al.: Transient inflammation and dysfunction of the eustachian tube secondary to multiple exposures of simulated gastroesophageal refluxant. Ann Otol Rhinol Laryngol 2001, 110:928–934.

    PubMed  CAS  Google Scholar 

  15. 15.

    Heavner SB, Hardy SM, White DR, et al.: Function of the eustachian tube after weekly exposure to pepsin/hydrochloric acid. Otolaryngol Head Neck Surg 2001, 125:123–129.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Johnston N, Dettmar PW, Lively MO, et al.: Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp 70) response: role in laryngopharyngeal reflux disease. Ann Otol Rhinol Laryngol 2006, 115:47–58.

    PubMed  Google Scholar 

  17. 17.

    Roberts NB. Review article: human pepsins-their multiplicity, function and role in reflux. Aliment Pharmacol Ther 2006, 24(Suppl 2):2–9.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Wittenborg MH, Neuhauser EB: Simple roentgenographic demonstration of eustachian tubes and abnormalities. Am J Roentgenol Radium Ther Nucl Med 1963, 89:1194–1200.

    PubMed  CAS  Google Scholar 

  19. 19.

    Holma B, Lindegren M, Andersen JM: pH effects on ciliomotility and morphology of respiratory mucosa. Arch Environ Health 1977, 32:216–226.

    PubMed  CAS  Google Scholar 

  20. 20.

    Ohashi Y, Nakai Y, Koshimo H, Esaki Y: Ciliary activity in the in vitro tubotympanum. Arch Otorhinolaryngol 1986, 243:317–319.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Park K, Bakaletz LO, Coticchia JM, Lim DJ: Effect of influenza A virus on ciliary activity and dye transport function in the chinchilla eustachian tube. Ann Otol Rhinol Laryngol 1993, 102:551–558.

    PubMed  CAS  Google Scholar 

  22. 22.

    Butehorn HF, Downs BW, Prazma J, Pillsbury HC: Acute gastroesophageal reflux and eustachian tube function [abstract]. ARO Abstracts of the Twenty-Second Midwinter Research Meeting. Mount Royal, NJ: Association for Research in Otolaryngology; 1999:199.

    Google Scholar 

  23. 23.

    Moody SA, Alper CM, Doyle WJ: Daily tympanometry in children during the cold season: association of otitis media with upper respiratory tract infections. Int J Pediatr Otorhinolaryngol 1998, 45:143–150.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Sudhoff H, Bucker R, Groll C, et al.: Tracing of gastric reflux into the middle ear in a Mongolian gerbil model. Otol Neurotol 2006, 28:124–128.

    Article  Google Scholar 

  25. 25.

    Rozmancic V, Velepic M, Ahel V, et al.: Prolonged esophageal pH monitoring in the evaluation of gastroesophageal reflux in children with chronic tubotympanal disorders. J Pediatr Gastroentrol Nutr 2002, 34:78–80.

    Google Scholar 

  26. 26.

    Keles B, Ozturk K, Gunel E, et al.: Pharyngeal reflux in children with chronic otitis media with effusion. Acta Otolaryngol 2004, 124:1178–1181.

    PubMed  Article  Google Scholar 

  27. 27.

    Martinsen TC, Bergh K, Waldum HL: Gastric juice: a barrier against infectious disease. Basic Clin Pharmacol Toxicol 2005, 96:94–102.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Jones AT, Roberts NB: Peptide maps of five human pepsin isoenzymes and other aspartic proteinases. J Chromatogr 1993, 646:207–212.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Tasker A, Dettmar PW, Panetti M, et al.: Reflux of gastric juice and glue ear in children. Lancet 2002, 359:493.

    PubMed  Article  Google Scholar 

  30. 30.

    Tasker A, Dettmar PW, Panetti M, et al.: Is gastric reflux a cause of otitis media with effusion in children? Laryngoscope 2002, 112:1930–1934.

    PubMed  Article  Google Scholar 

  31. 31.

    He Z, O’Reilly RC, Bolling L, et al.: Detection of gastric pepsin in the middle ear fluid of children with otitis media. Otolaryngol Head Neck Surg 2007, 137:59–64.

    PubMed  Article  Google Scholar 

  32. 32.

    Krishnan U, Mitchell JD, Messina I, et al.: Assay of tracheal pepsin as a marker of reflux aspiration. J Pediatr Gastroenterol Nutr 2002, 35:303–308.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Crapko M, Kerschner JE, Syring M, Johnston N: Role of extra-esophageal reflux in chronic otitis media with effusion. Laryngoscope 2007, 117:1419–1423.

    PubMed  Article  Google Scholar 

  34. 34.

    Lieu JE, Muthappan G, Uppaluri R: Association of reflux with otitis media in children. Otolaryngol Head Neck Surg 2005, 133:357–361.

    PubMed  Article  Google Scholar 

  35. 35.

    Sone M, Yamamuro Y, Hayashi H, et al.: Otitis media in adults as a symptom of gastroesophageal reflux. Otolaryngol Head Neck Surg 2007, 136:19–22.

    PubMed  Article  Google Scholar 

  36. 36.

    Sone M, Yamamuro Y, Hayashi H, et al.: Prediction of gastroesophageal reflux in otitis media with effusion in adults. Acta Otolaryngol 2007, 127:470–473.

    PubMed  Article  Google Scholar 

  37. 37.

    Antonelli PJ, Lloyd KM, Lee JC: Gastric reflux is uncommon in acute post-tympanostomy otorrhea. Otolaryngol Head Neck Surg 2005, 132:523–526.

    PubMed  Article  Google Scholar 

  38. 38.

    Bates DD, Lively M, Koufman J, et al.: Pepsin not detected in middle ear effusions in children [abstract]. Otolaryngol Head Neck Surg 2006, 135(2 Suppl):99.

    Article  Google Scholar 

  39. 39.

    El-Fattah A, Maksoud G, Ramadan A, et al.: Pepsin assay: a marker for reflux in pediatric glue ear. Otolaryngol Head Neck Surg 2007, 136:464–470.

    Article  Google Scholar 

  40. 40.

    Foster C, Aktar A, Kopf D, et al.: Pepsinogen C: a type 2 cell-specific protease. Am J Physiol Lung Cell Mol Physiol 2004, 286:L382–L387.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Taggart RT, Cass LG, Mohandas TK, et al.: Human pepsinogen C (progastricsin): isolation of cDNA clones, localization to chromosome 6, and sequence homology with pepsinogen A. J Biol Chem 1989, 264:375–379.

    PubMed  CAS  Google Scholar 

  42. 42.

    Gupta SK, Hassall E, Chiu YL, et al.: Presenting symptoms of nonerosive and erosive esophagitis in pediatric patients. Dig Dis Sci 2006, 51:858–863.

    PubMed  Article  Google Scholar 

  43. 43.

    Bauman NM, Bishop WP, Sandler AD, Smith RJ: Value of pH probe testing in pediatric patients with extraesophageal manifestations of gastroesophageal reflux disease: a retrospective review. Ann Otol Rhinol Laryngol Suppl 2000, 184:18–24.

    PubMed  CAS  Google Scholar 

  44. 44.

    Nassif PS, Simpson SQ, Izzo AA, Nicklaus PJ: Interleukin-8 concentration predicts the neutrophil count in middle ear effusion. Laryngoscope 1997, 107:1223–1227.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Chung MH, Choi JY, Lee WS, Yoon JH: Compositional difference in middle ear effusion: mucous versus serous. Laryngoscope 2002, 112:152–155.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Robert C. O’Reilly.

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He, Z., O’Reilly, R.C. & Mehta, D. Gastric pepsin in middle ear fluid of children with otitis media: Clinical implications. Curr Allergy Asthma Rep 8, 513–518 (2008).

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  • Otitis Medium
  • Eustachian Tube
  • Chronic Otitis Medium
  • Eustachian Tube Dysfunction
  • Eustachian Tube Function