Interaction Between Allergy and Middle Ear Infection

Otitis (DP Skoner, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Otitis


Purpose of Review

Recent studies have attempted to identify interactions among the causes of otitis media with effusion (OME). This review discusses the interaction between allergy and infection with regard to host and environmental factors in terms of the development of OME.

Recent Findings

Protection of the upper airway against microbial invasion requires active interaction between the defense mechanisms of the respiratory epithelium, including innate and adaptive immunity, and mechanical factors. The impairment of these defenses due to allergy and/or increased bacterial resistance may lead to increased susceptibility to infectious organisms in the respiratory tract and middle ear mucosa. Recent genetic studies have provided valuable information about the association of Toll-like receptor signaling variations with clinical phenotypes and the risk of infection in the middle ear.


Among the causal factors of OME, allergy not only induces an inflammatory reaction in the middle ear cavity but also facilitates the invasion of infectious pathogens. There is also evidence that allergy can affect the susceptibility of patients to infection of the upper respiratory tract, including the middle ear cavity.


Otitis media with effusion Allergy Infection Innate immunity Acquired immunity 


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

  1. 1.
    Smirnova MG, Kiselev SL, Gnuchev NV, Birchall JP, Pearson JP. Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion. Eur Cytokine Netw. 2002;13(2):161–72.PubMedGoogle Scholar
  2. 2.
    Kubba H, Pearson JP, Birchall JP. The aetiology of otitis media with effusion: a review. Clin Otolaryngol Allied Sci. 2000;25(3):181–94.PubMedCrossRefGoogle Scholar
  3. 3.
    Alles R, Parikh A, Hawk L, Darby Y, Romero JN, Scadding G. The prevalence of atopic disorders in children with chronic otitis media with effusion. Pediatric allergy and immunology. 2001;12(2):102–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Talbot TR, Hartert TV, Mitchel E, Halasa NB, Arbogast PG, Poehling KA, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005;352(20):2082–90. doi:10.1056/NEJMoa044113.PubMedCrossRefGoogle Scholar
  5. 5.
    Juhn YJ, Kita H, Yawn BP, Boyce TG, Yoo KH, McGree ME, et al. Increased risk of serious pneumococcal disease in patients with asthma. The Journal of allergy and clinical immunology. 2008;122(4):719–23. doi:10.1016/j.jaci.2008.07.029.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Cernelc D, Gerbec M, Cernelc P. Comparative study of virological infections in asthmatic and nonasthmatic children. Acta Allergol. 1975;30(6):423–33.PubMedCrossRefGoogle Scholar
  7. 7.
    Halablab MA, Hijazi SM, Fawzi MA, Araj GF. Staphylococcus aureus nasal carriage rate and associated risk factors in individuals in the community. Epidemiol Infect. 2010;138(5):702–6. doi:10.1017/S0950268809991233.PubMedCrossRefGoogle Scholar
  8. 8.
    Warner JA, McGirt LY, Beck LA. Biomarkers of Th2 polarity are predictive of staphylococcal colonization in subjects with atopic dermatitis. Br J Dermatol. 2009;160(1):183–5. doi:10.1111/j.1365-2133.2008.08905.x.PubMedCrossRefGoogle Scholar
  9. 9.
    Leung AD, Schiltz AM, Hall CF, Liu AH. Severe atopic dermatitis is associated with a high burden of environmental Staphylococcus aureus. Clin Exp Allergy. 2008;38(5):789–93. doi:10.1111/j.1365-2222.2008.02964.x.PubMedCrossRefGoogle Scholar
  10. 10.
    Newacheck PW, Stoddard JJ. Prevalence and impact of multiple childhood chronic illnesses. J Pediatr. 1994;124(1):40–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Luong A, Roland PS. The link between allergic rhinitis and chronic otitis media with effusion in atopic patients. Otolaryngologic clinics of North America. 2008;41(2):311–23. doi:10.1016/ Scholar
  12. 12.•
    Hurst DS. The role of allergy in otitis media with effusion. Otolaryngologic clinics of North America. 2011;44(3):637–54. doi:10.1016/j.otc.2011.03.009.viii-ix. Up-to-date review on the relationship between allergy and eustachian tube dysfunction.
  13. 13.
    Chantzi FM, Kafetzis DA, Bairamis T, Avramidou C, Paleologou N, Grimani I, et al. IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion. Allergy. 2006;61(3):332–6. doi:10.1111/j.1398-9995.2006.00971.x.PubMedCrossRefGoogle Scholar
  14. 14.
    Miceli Sopo S, Zorzi G, Calvani Jr M. Should we screen every child with otitis media with effusion for allergic rhinitis? Arch Dis Child. 2004;89(3):287–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Tewfik TL, Mazer B. The links between allergy and otitis media with effusion. Curr Opin Otolaryngol Head Neck Surg. 2006;14(3):187–90. doi:10.1097/01.moo.0000193190.24849.f0.PubMedCrossRefGoogle Scholar
  16. 16.
    Bentdal YE, Nafstad P, Karevold G, Kvaerner KJ. Acute otitis media in schoolchildren: allergic diseases and skin prick test positivity. Acta oto-laryngologica. 2007;127(5):480–5. doi:10.1080/00016480600895128.PubMedCrossRefGoogle Scholar
  17. 17.
    Bjur KA, Lynch RL, Fenta YA, Yoo KH, Jacobson RM, Li X, et al. Assessment of the association between atopic conditions and tympanostomy tube placement in children. Allergy Asthma Proc. 2012;33(3):289–96. doi:10.2500/aap.2012.33.3529.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Hurst DS. Association of otitis media with effusion and allergy as demonstrated by intradermal skin testing and eosinophil cationic protein levels in both middle ear effusions and mucosal biopsies. Laryngoscope. 1996;106(9 Pt 1):1128–37.PubMedCrossRefGoogle Scholar
  19. 19.
    Hurst DS, Venge P. Evidence of eosinophil, neutrophil, and mast-cell mediators in the effusion of OME patients with and without atopy. Allergy. 2000;55(5):435–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Bluestone CD, Stephenson JS, Martin LM. Ten-year review of otitis media pathogens. Pediatr Infect Dis J. 1992;11(8 Suppl):S7–11.PubMedCrossRefGoogle Scholar
  21. 21.
    Post JC, Preston RA, Aul JJ, Larkins-Pettigrew M, Rydquist-White J, Anderson KW, et al. Molecular analysis of bacterial pathogens in otitis media with effusion. JAMA. 1995;273(20):1598–604.PubMedCrossRefGoogle Scholar
  22. 22.
    Matar GM, Sidani N, Fayad M, Hadi U. Two-step PCR-based assay for identification of bacterial etiology of otitis media with effusion in infected Lebanese children. J Clin Microbiol. 1998;36(5):1185–8.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Rayner MG, Zhang Y, Gorry MC, Chen Y, Post JC, Ehrlich GD. Evidence of bacterial metabolic activity in culture-negative otitis media with effusion. JAMA. 1998;279(4):296–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Gok U, Bulut Y, Keles E, Yalcin S, Doymaz MZ. Bacteriological and PCR analysis of clinical material aspirated from otitis media with effusions. International journal of pediatric otorhinolaryngology. 2001;60(1):49–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Palmu AA, Saukkoriipi PA, Lahdenkari MI, Kuisma LK, Makela PH, Kilpi TM, et al. Does the presence of pneumococcal DNA in middle-ear fluid indicate pneumococcal etiology in acute otitis media? J Infect Dis. 2004;189(5):775–84. doi:10.1086/381765.PubMedCrossRefGoogle Scholar
  26. 26.
    Peizhong L, Whatmough K, Birchall JP, Wilson JA, Pearson JP. Does the bacterial DNA found in middle ear effusions come from viable bacteria? Clin Otolaryngol Allied Sci. 2000;25(6):570–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Fergie N, Bayston R, Pearson JP, Birchall JP. Is otitis media with effusion a biofilm infection? Clin Otolaryngol Allied Sci. 2004;29(1):38–46.PubMedCrossRefGoogle Scholar
  28. 28.
    Hoa M, Syamal M, Schaeffer MA, Sachdeva L, Berk R, Coticchia J. Biofilms and chronic otitis media: an initial exploration into the role of biofilms in the pathogenesis of chronic otitis media. American journal of otolaryngology. 2010;31(4):241–5. doi:10.1016/j.amjoto.2009.02.015.PubMedCrossRefGoogle Scholar
  29. 29.
    Tawfik SA, Ibrahim AA, Talaat IM, El-Alkamy SS, Youssef A. Role of bacterial biofilm in development of middle ear effusion. Eur Arch Otorhinolaryngol. 2016. doi:10.1007/s00405-016-4094-2.PubMedGoogle Scholar
  30. 30.
    Hall-Stoodley L, Stoodley P. Biofilm formation and dispersal and the transmission of human pathogens. Trends Microbiol. 2005;13(1):7–10. doi:10.1016/j.tim.2004.11.004.PubMedCrossRefGoogle Scholar
  31. 31.
    Lewis K. Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol. 2008;322:107–31.PubMedGoogle Scholar
  32. 32.
    Weimer KE, Armbruster CE, Juneau RA, Hong W, Pang B, Swords WE. Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J Infect Dis. 2010;202(7):1068–75. doi:10.1086/656046.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.•
    Daniel M, Imtiaz-Umer S, Fergie N, Birchall JP, Bayston R. Bacterial involvement in otitis media with effusion. International journal of pediatric otorhinolaryngology. 2012;76(10):1416–22. doi:10.1016/j.ijporl.2012.06.013. Study demonstrating live bacteria in more than 90% of middle ear effusions in children.
  34. 34.
    Bakaletz LO. Immunopathogenesis of polymicrobial otitis media. J Leukoc Biol. 2010;87(2):213–22. doi:10.1189/jlb.0709518.PubMedCrossRefGoogle Scholar
  35. 35.
    Lim JH, Ha U, Sakai A, Woo CH, Kweon SM, Xu H, et al. Streptococcus pneumoniae synergizes with nontypeable Haemophilus influenzae to induce inflammation via upregulating TLR2. BMC Immunol. 2008;9:40. doi:10.1186/1471-2172-9-40.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Krishnamurthy A, McGrath J, Cripps AW, Kyd JM. The incidence of Streptococcus pneumoniae otitis media is affected by the polymicrobial environment particularly Moraxella catarrhalis in a mouse nasal colonisation model. Microbes Infect. 2009;11(5):545–53. doi:10.1016/j.micinf.2009.03.001.PubMedCrossRefGoogle Scholar
  37. 37.
    Kania RE, Lamers GE, Vonk MJ, Dorpmans E, Struik J, Tran Ba Huy P, et al. Characterization of mucosal biofilms on human adenoid tissues. Laryngoscope. 2008;118(1):128–34. doi:10.1097/MLG.0b013e318155a464.PubMedCrossRefGoogle Scholar
  38. 38.
    Ebert Jr CS, Pollock HW, Dubin MG, Scharer SS, Prazma J, McQueen CT, et al. Effect of intranasal histamine challenge on Eustachian tube function. International journal of pediatric otorhinolaryngology. 2002;63(3):189–98.PubMedCrossRefGoogle Scholar
  39. 39.
    Skoner DP, Doyle WJ, Boehm S, Fireman P. Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge. Ann Allergy. 1991;67(6):619–24.PubMedGoogle Scholar
  40. 40.
    Doyle WJ, Ingraham AS, Fireman P. The effects of intranasal histamine challenge on eustachian tube function. The Journal of allergy and clinical immunology. 1985;76(4):551–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Hardy SM, Heavner SB, White DR, McQueen CT, Prazma J, Pillsbury HC. Late-phase allergy and eustachian tube dysfunction. Otolaryngology--head and neck surgery. 2001;125(4):339–45. doi:10.1067/mhn.2001.119140.PubMedCrossRefGoogle Scholar
  42. 42.
    Fireman P. Otitis media and eustachian tube dysfunction: connection to allergic rhinitis. The Journal of allergy and clinical immunology. 1997;99(2):S787–97.PubMedCrossRefGoogle Scholar
  43. 43.
    Pelikan Z. The role of nasal allergy in chronic secretory otitis media. Ann Allergy Asthma Immunol. 2007;99(5):401–7. doi:10.1016/S1081-1206(10)60563-7.PubMedCrossRefGoogle Scholar
  44. 44.
    Bernstein JM. Role of allergy in eustachian tube blockage and otitis media with effusion: a review. Otolaryngology--head and neck surgery. 1996;114(4):562–8.PubMedCrossRefGoogle Scholar
  45. 45.••
    Murphy TF, Chonmaitree T, Barenkamp S, Kyd J, Nokso-Koivisto J, Patel JA, et al. Panel 5: microbiology and immunology panel. Otolaryngology--head and neck surgery. 2013;148(4 Suppl):E64–89. doi:10.1177/0194599812459636. Up-to-date review of the progress on the virology, bacteriology, and immunology related to otitis media.
  46. 46.
    Vareille M, Kieninger E, Edwards MR, Regamey N. The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev. 2011;24(1):210–29. doi:10.1128/CMR.00014-10.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Ogra PL. Ageing and its possible impact on mucosal immune responses. Ageing Res Rev. 2010;9(2):101–6. doi:10.1016/j.arr.2009.07.007.PubMedCrossRefGoogle Scholar
  48. 48.
    Van Kempen MJ, Rijkers GT, Van Cauwenberge PB. The immune response in adenoids and tonsils. Int Arch Allergy Immunol. 2000;122(1):8–19. 24354.PubMedCrossRefGoogle Scholar
  49. 49.
    Casselbrant ML. What is wrong in chronic adenoiditis/tonsillitis anatomical considerations. International journal of pediatric otorhinolaryngology. 1999;49 Suppl 1:S133–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Marseglia GL, Poddighe D, Caimmi D, Marseglia A, Caimmi S, Ciprandi G, et al. Role of adenoids and adenoiditis in children with allergy and otitis media. Current allergy and asthma reports. 2009;9(6):460–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Skoner AR, Skoner KR, Skoner DP. Allergic rhinitis, histamine, and otitis media. Allergy Asthma Proc. 2009;30(5):470–81. doi:10.2500/aap.2009.30.3272.PubMedCrossRefGoogle Scholar
  52. 52.•
    Zelazowska-Rutkowska B, Wysocka J, Skotnicka B. Chosen factors of T and B cell apoptosis in hypertrophic adenoid in children with otitis media with effusion. International journal of pediatric otorhinolaryngology. 2010;74(6):698–700. doi:10.1016/j.ijporl.2010.02.024. Study suggesting the immunological role of the adenoid tissue with regulating the lymphocytes.
  53. 53.•
    Kotowski M, Niedzielski A, Niedzielska G, Lachowska-Kotowska P. Dendritic cells and lymphocyte subpopulations of the adenoid in the pathogenesis of otitis media with effusion. International journal of pediatric otorhinolaryngology. 2011;75(2):265–9. doi:10.1016/j.ijporl.2010.11.014. Study explaining the influence of immunological status of adenoid on the development of OME.
  54. 54.
    Bernstein JM, Ballow M, Xiang S, O’Neil K. Th1/Th2 cytokine profiles in the nasopharyngeal lymphoid tissues of children with recurrent otitis media. The Annals of otology, rhinology, and laryngology. 1998;107(1):22–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Yeo SG, Park DC, Lee SK, Cha CI. Relationship between effusion bacteria and concentrations of immunoglobulin in serum and effusion fluid in otitis media with effusion patients. International journal of pediatric otorhinolaryngology. 2008;72(3):337–42. doi:10.1016/j.ijporl.2007.11.005.PubMedCrossRefGoogle Scholar
  56. 56.
    Kim WJ, Kim BG, Chang KH, Oh JH. Detection of bacteria in middle ear effusions based on the presence of allergy: does allergy augment bacterial infection in the middle ear? J Otolaryngol Head Neck Surg. 2015;44:58. doi:10.1186/s40463-015-0111-5.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Hirano T, Kodama S, Moriyama M, Kawano T, Suzuki M. The role of Toll-like receptor 4 in eliciting acquired immune responses against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein. International journal of pediatric otorhinolaryngology. 2009;73(12):1657–65. doi:10.1016/j.ijporl.2009.08.015.PubMedCrossRefGoogle Scholar
  58. 58.
    Leichtle A, Hernandez M, Pak K, Yamasaki K, Cheng CF, Webster NJ, et al. TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media. Innate Immun. 2009;15(4):205–15. doi:10.1177/1753425909103170.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol. 2001;1(1):69–75. doi:10.1038/35095579.PubMedCrossRefGoogle Scholar
  60. 60.
    Holt PG, Macaubas C, Prescott SL, Sly PD. Microbial stimulation as an aetiologic factor in atopic disease. Allergy. 1999;54 Suppl 49:12–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Emonts M, Veenhoven RH, Wiertsema SP, Houwing-Duistermaat JJ, Walraven V, de Groot R, et al. Genetic polymorphisms in immunoresponse genes TNFA, IL6, IL10, and TLR4 are associated with recurrent acute otitis media. Pediatrics. 2007;120(4):814–23. doi:10.1542/peds.2007-0524.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, St. Paul’s HospitalThe Catholic University of KoreaDongdaemun-guRepublic of Korea
  2. 2.Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Seoul St. Mary’s HospitalThe Catholic University of KoreaSeocho-guRepublic of Korea

Personalised recommendations