Otitis Media with Effusion in Children and the Impact of Risk Factors on Serum Cytokine Levels

Document Type : Original


1 Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran.

2 ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences,Tehran,Iran.

3 ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences,Tehran,Iran.

4 Department of Health, Epidemiologist, Mississippi State, United States.

5 Department of Radiology, University of Mississippi Medical Center, Mississippi State, United States.


To evaluate the role of allergic-type and infectious-type cytokines in children with chronic otitis media with effusion (OME)
 Materials and Methods:
We investigated serum levels of interleukins (IL)-4, IL-5, and IL-13, along with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), by enzyme-linked immunosorbent assay (ELISA) in 35 children with OME and 28 healthy controls.
Children with OME had significantly higher levels of IL-5 in comparison with the control group, ranging from 1 pg/ml in cases to 0.04 pg/ml in controls (P=0.009). However, after adjusting for confounding variables, there was no significant difference in serum levels of IL-13, IL-4, IFN-γ, or TNF-α between the two groups (P=0.287, P=0.627, P=0.793, and P=0.217, respectively)
The findings of this study suggest that in comparison with the control group, serum IL-5 levels were elevated in OME cases.


Main Subjects

1. Stool SE, Berman S, Carney CJ, Cooley JR, Culpepper L, Eavey RD, Feagans LV, Finitzo T, Friedman EM. Managing otitis media with effusion in young children. Agency for Health Care Policy and Research (AHCPR): AHCPR Clinical Practice Guidelines.  1994;6(10): 766-73.
2. Shekelle P, Chan LS, Mangione-Smith R, Corley PM, Morphew T, Morton S. Diagnosis, Natural History, and Late Effects of Otitis Media with Effusion. Agency for Healthcare Research and Quality (US). 2002 Jun;(55):1-5.
3. Pichichero ME. Otitis media. Pediatric clinics of North America. 2013;60(2):391–407.
4. Li JD, Hermansson A, Ryan AF, Bakaletz LO, Brown SD, Cheeseman MT, et al. Panel 4: Recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models. Otolaryngol Head Neck Surg. 2013;148(4 Suppl): E52–63.
5. Postelnicu V, Iosif O, Bidiga R, Rosu V, Oproiu G. Acute middle ear pathology in children with upper respiratory tract infections. Romanian Journal of Rhinology. 2012;2(8): 217-24.
6. Bluestone CD, Klein JO. Otitis media with effusion. 3rd ed. Pediatric Otolaryngology. 1996:388-589.
7. Healy G. Otitis media and middle ear effusions. 15th ed. Otorhinolaryngology ,Head and Neck Surgery. 1996:1003-9.
8. Morris PS, Leach AJ, Silberberg P, Mellon G, Wilson C, Hamilton E, et al. Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross-sectional survey. BMC Pediatr. 2005;5:27.
9. Aithal S, Aithal V, Kei J, Driscoll C. Conductive hearing loss and middle ear pathology in young infants referred through a newborn universal hearing screening program in Australia. J Am Acad Audiol. 2012; 23(9):673–85.
10. Klausen O, Moller P, Holmefjord A, Reisaeter S, Asbjornsen A. Lasting effects of otitis media with effusion on language skills and listening performance. Acta Oto-laryngologica Supplementum. 2000; 543: 73–6.
11. Minovi A, Dazert S. Diseases of the middle ear in childhood. Laryngo-rhino-otologie. 2014; 93 (Suppl 1): S1–23.
12. Bernstein JM. Immunologic reactivity in the middle ear in otitis media with effusion. Otolaryngologic Clinics N Am. 1991; 24(4): 845-58.
13. Bernstein JM, Doyle WJ. Role of IgE-mediated hypersensitivity in otitis media with effusion: pathophysiologic considerations. Annals Otol Rhinol Laryngol Suppl. 1994; 163:15–9.
14. Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Rev Immunol. 2001; 1(1):69–75.
15. Prioult G, Nagler-Anderson C. Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation? Immunological Rev. 2005; 206: 204–18.
16. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol. 1989; 7:145–73.
17. Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol. 2003;111(2 Suppl):S460–75.
18. Rosenfeld RM, Casselbrant ML, Hannley MT. Implications of the AHRQ evidence report on acute otitis media. Otolaryngol Head Neck Surg. 2001;125(5):440–8; discussion 39.
19. Nguyen LH, Manoukian JJ, Sobol SE, Tewfik TL, Mazer BD, Schloss MD, et al. Similar allergic inflammation in the middle ear and the upper airway: evidence linking otitis media with effusion to the united airways concept. J Allergy Clin Immunol. 2004;114(5):1110–5.
20. Zielnik-Jurkiewicz B, Stankiewicz-Szymczak W. Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion. Eur Arch Otorhinolaryngol. 2016;273(6):1369–78.
21. Wright ED, Hurst D, Miotto D, Giguere C, Hamid Q. Increased expression of major basic protein (MBP) and interleukin-5(IL-5) in middle ear biopsy specimens from atopic patients with persistent otitis media with effusion. Otolaryngol Head Neck Surg. 2000;123(5):533–8.
22. Shim HJ, Park DC, Lee YC, Eun YG, Yeo SG. Expression of GATA3, T-bet, IL-4, and IFN-gamma mRNA in the effusion of OME patients. Int J Pediatr Otorhinolaryngol. 2009;73(8):1119–23.
23. Kariya S, Okano M, Hattori H, Sugata Y, Matsumoto R, Fukushima K, et al. TH1/TH2 and regulatory cytokines in adults with otitis media with effusion. Otol Neurotol. 2006;27(8):1089–93.
24. 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 Network. 2002;13(2):161–72.
25. Kwon C, Lee HY, Kim MG, Boo SH, Yeo SG. Allergic diseases in children with otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2013; 77(2): 158–61.
26. Smirnova MG, Birchall JP, Pearson JP. The immunoregulatory and allergy-associated cytokines in the aetiology of the otitis media with effusion. Mediators Inflamm. 2004;13(2):75–88.
27. Bernstein JM, Ballow M, Xiang S, O'Neil K. Th1/Th2 cytokine profiles in the nasopharyngeal lymphoid tissues of children with recurrent otitis media. Ann Otol Rhinol Laryngol.1998;107(1):22-7.
28. Johnston BN, Preciado DA, Ondrey FG, Daly KA. Presence of otitis media with effusion and its risk factors affect serum cytokine profile in children. Int J Pediatr Otorhinolaryngol. 2008;72(2):209–14.
29. Sophia A, Isaac R, Rebekah G, Brahmadathan K, Rupa V. Risk factors for otitis media among preschool, rural Indian children. Int J Pediatr Otorhinolaryngol. 2010;74(6):677–83.
30. Xenellis J, Paschalidis J, Georgalas C, Davilis D, Tzagaroulakis A, Ferekidis E. Factors influencing the presence of otitis media with effusion 16 months after initial diagnosis in a cohort of school-age children in rural Greece: a prospective study. Int J Pediatr Otorhinolaryngol. 2005;69(12):1641–7.
31. Humaid AH, Ashraf AH, Masood KA, Nuha AH, Saleh AD, Awadh AM. Prevalence and risk factors of Otitis Media with effusion in school children in Qassim Region of Saudi Arabia. Int Journal Health Sci. 2014;8(4):325–34.
32. Martines F, Bentivegna D, Maira E, Sciacca V, Martines E. Risk factors for otitis media with effusion: case-control study in Sicilian schoolchildren. Int J Pediatr Otorhinolaryngol. 2011; 75(6):754–9.
33. Tong MC, Yue V, Ku PK, Lo PS, Wong EM, van Hasselt CA. Risk factors for otitis media with effusion in Chinese schoolchildren: a nested case-control study and review of the literature. Int J Pediatr Otorhinolaryngol. 2006;70(2):213–9.
34. Marseglia GL, Pagella F, Caimmi D, Caimmi S, Castellazzi AM, Poddighe D, et al. Increased risk of otitis media with effusion in allergic children presenting with adenoiditis. Otolaryngol Head Neck Surg. 2008;138(5):572–5.
35. Caylan R, Bektas D, Atalay C, Korkmaz O. Prevalence and risk factors of otitis media with effusion in Trabzon, a city in northeastern Turkey, with an emphasis on the recommendation of OME screening. Eur Arch Otorhinolaryngol. 2006; 263(5): 404–8.
36. Zielhuis GA, Rach GH, van den Bosch A, van den Broek P. The prevalence of otitis media with effusion: a critical review of the literature. Clin Otolaryngol Allied Sci. 1990;15(3):283–8.
37. Damoiseaux RA, Rovers MM, Van Balen FA, Hoes AW, de Melker RA. Long-term prognosis of acute otitis media in infancy: determinants of recurrent acute otitis media and persistent middle ear effusion. Fam Pract. 2006;23(1):40–5.
38. Gryczynska D, Kobos J, Zakrzewska A. Relationship between passive smoking, recurrent respiratory tract infections and otitis media in children. Int J Pediatr Otorhinolaryngol. 1999;49 Suppl 1: S275–8.
39. Vassallo R, Tamada K, Lau JS, Kroening PR, Chen L. Cigarette smoke extract suppresses human dendritic cell function leading to preferential induction of Th-2 priming. J Immunol. 2005; 175(4): 2684–91.
40. Rumold R, Jyrala M, Diaz-Sanchez D. Secondhand smoke induces allergic sensitization in mice. J Immunol. 2001;167(8):4765–70.
41. Feleszko W, Zawadzka-Krajewska A, Matysiak K, Lewandowska D, Peradzynska J, Dinh QT, et al. Parental tobacco smoking is associated with augmented IL-13 secretion in children with allergic asthma. J Allergy Clin Immunol. 2006;117(1):
42. Wilson KM, Wesgate SC, Pier J, Weis E, Love T, Evans K, et al. Secondhand smoke exposure and serum cytokine levels in healthy children. Cytokine. 2012; 60(1):34–7.
43. Kiris M, Muderris T, Kara T, Bercin S, Cankaya H, Sevil E. Prevalence and risk factors of otitis media with effusion in school children in Eastern Anatolia. Int J Pediatr Otorhinolaryngol. 2012; 76(7):1030–5.
44. Lack G, Caulfield H, Penagos M. The link between otitis media with effusion and allergy: a potential role for intranasal corticosteroids. Pediatr Allergy Immunol. 2011;22(3):258–66.
45. Souter MA, Mills NA, Mahadevan M, Douglas G, Ellwood PE, Asher MI, et al. The prevalence of atopic symptoms in children with otitis media with effusion. Otolaryngol Head Neck Surg. 2009; 141(1): 104-7.
46. Aydemir G, Ozkurt FE. Otitis media with effusion in primary schools in Princes' Islands, Istanbul: prevalence and risk factors. J Int Med Res. 2011; 39(3):866-72.
47. Wellington M, Hall CB. Pacifier as a risk factor for acute otitis media. Pediatr. 2002;109(2):351–2.
48. Niemela M, Uhari M, Mottonen M. A pacifier increases the risk of recurrent acute otitis media in children in day care centers. Pediatr. 1995;96
(5 Pt 1):884-8.