{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:29Z","timestamp":1791229649296,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>This review studies the potential relationship between the pathogenesis of allergic rhinitis (AR) and otitis media with effusion (OME) in both adults and children, applying the modified Bradford Hill criteria. While AR and OME are distinct conditions, several epidemiological and experimental studies suggest a significant association, primarily through allergic mechanisms such as Th-2 immune responses, Eustachian tube dysfunction, and inflammatory mediators in the middle ear. Given the substantial diversity and, in many instances, the \u201clow quality\u201d of related studies when assessed against the standards of modern evidence-based medicine, employing a structured framework like the modified Bradford Hill criteria is beneficial for investigating and establishing causality. This approach, which allows a wide range of diverse studies to be classified as direct, mechanistic, or parallel evidence, supports the notion that management of the allergic immune response may improve OME outcomes, although the inconsistencies among studies require further research. Despite current guidelines recommending against the use of antiallergic medications, the application of the above criteria suggests that proper diagnosis and treatment of allergic rhinitis should be strongly considered in adults and children with OME.<\/jats:p>","DOI":"10.3390\/cells14110805","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:07:58Z","timestamp":1748592478000},"page":"805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Is Allergic Rhinitis Related to Otitis Media with Effusion in Adults and Children? Applying Epidemiological Guidelines for Causation"],"prefix":"10.3390","volume":"14","author":[{"given":"Ioannis Michael","family":"Vlastos","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7720-090X","authenticated-orcid":false,"given":"Natalia","family":"Tsotsiou","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohannad","family":"Almomani","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Doulaptsi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Heraklion University Hospital, 71500 Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3196-2176","authenticated-orcid":false,"given":"Alexandros","family":"Karatzanis","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Heraklion University Hospital, 71500 Crete, Greece"},{"name":"Laboratory of Translational Otorhinolaryngology Research, School of Medicine, University of Crete, 71500 Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Prokopakis","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Heraklion University Hospital, 71500 Crete, Greece"},{"name":"Laboratory of Translational Otorhinolaryngology Research, School of Medicine, University of Crete, 71500 Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","first-page":"295","article-title":"Section of Occupational Medicine the Environment and Disease: Association or Causation","volume":"58","author":"Hill","year":"1965","journal-title":"Proc. R. Soc. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Howick, J., Glasziou, P., and Aronson, J.K. (2009). The Evolution of Evidence Hierarchies: What can Bradford Hill\u2019s \u201cGuidelines for Causation\u201d Contribute?. arXiv.","DOI":"10.1258\/jrsm.2009.090020"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Georgalas, C., Vlastos, I., Picavet, V., Van Drunen, C., Garas, G., and Prokopakis, E. (2014). Is Chronic Rhinosinusitis Related to Allergic Rhinitis in Adults and Children? Applying Epidemiological Guidelines for Causation. arXiv.","DOI":"10.1111\/all.12413"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Byeon, H. (2019). The Association Between Allergic Rhinitis and Otitis Media: A National Representative Sample of in South Korean Children. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-38369-7"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4168\/aair.2016.8.5.445","article-title":"AntibiSynergistic Effect of Dermatophagoides farinae and Lipopolysaccharides in Human Middle Ear Epithelial Cells","volume":"8","author":"Lee","year":"2016","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0091-6749(87)80012-X","article-title":"Eustachian tube obstruction (ETO) after histamine nasal provocation\u2014A double-blind dose-response study","volume":"79","author":"Skoner","year":"1987","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/0091-6749(83)90459-1","article-title":"Immunologic-mediated eustachian tube obstruction: A double-blind crossover study","volume":"71","author":"Friedman","year":"1983","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1097\/MAO.0b013e3181b0d0f3","article-title":"Audiometric Changes in Chronic Secretory Otitis Media Due to Nasal Allergy","volume":"30","author":"Pelikan","year":"2009","journal-title":"Otol. Neurotol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/0091-6749(85)90694-3","article-title":"Induction of eustachian tube dysfunction with histamine nasal provocation","volume":"76","author":"Walker","year":"1985","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3109\/00016488809125100","article-title":"The Role of Nasal Allergy in Otitis Media with Effusion a Clinical Study","volume":"458","author":"Tomonaga","year":"1988","journal-title":"Acta Otolaryngol."},{"key":"ref_11","first-page":"205","article-title":"Allergy: A leading role in otitis media with effusion","volume":"15","author":"Bellioni","year":"1988","journal-title":"Allergol. Immunopathol."},{"key":"ref_12","first-page":"215","article-title":"Role of food allergy in serous otitis media","volume":"73","author":"Nsouli","year":"1994","journal-title":"Ann. Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1177\/00034894760850S216","article-title":"Middle Ear Effusion in Experimental Hypersensitivity","volume":"85","author":"Miglets","year":"1976","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1001\/archotol.1984.00800340020004","article-title":"Eustachian Tube Obstruction After Provocative Nasal Antigen Challenge","volume":"110","author":"Doyle","year":"1984","journal-title":"Arch. Otolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1067\/mhn.2001.119140","article-title":"Late-phase allergy and eustachian tube dysfunction","volume":"125","author":"Hardy","year":"2001","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3109\/00016489309126186","article-title":"Regional blood flow volume in the eustachian tube","volume":"113","author":"Minami","year":"1993","journal-title":"Acta Otolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijporl.2016.02.018","article-title":"Otitis media with effusion in an allergic animal model: A functional and morphological study","volume":"84","author":"Kim","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1177\/00034894800890S337","article-title":"Relation Between Nasal and Middle Ear Allergy Experimental Study","volume":"89","author":"Okazaki","year":"1980","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0385-8146(12)80072-1","article-title":"Type I Allergic Reactions of the Middle Ear and Eustachian Tube: An Experimental Study","volume":"17","author":"Tomonaga","year":"1990","journal-title":"Auris Nasus Larynx"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1001\/archotol.1985.00800100050004","article-title":"The Role of Allergy in the Pathogenesis of Otitis Media with Effusion","volume":"111","author":"Doyle","year":"1985","journal-title":"Arch. Otolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1001\/archotol.1990.01870030095016","article-title":"Influence of Nasal Allergic Reactions on the Clearance of Middle Ear Effusion","volume":"116","author":"Mogi","year":"1990","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_22","first-page":"155","article-title":"The role of type I allergy in secretory otitis media and mast cells in the middle ear mucosa","volume":"493","author":"Mogi","year":"1992","journal-title":"Acta Otolaryngol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bjorl.2020.09.011","article-title":"Morphological and Pathological Changes of Eustachian Tube Mucosa in an Animal Model of Eosinophilic Otitis Media","volume":"88","author":"Yang","year":"2022","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.otohns.2007.02.016","article-title":"Immune Modulatory Oligonucleotides in the Prevention and Treatment of OVA-Induced Eustachian Tube Dysfunction in Rats","volume":"137","author":"Blanks","year":"2007","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1067\/mhn.2002.126901","article-title":"The role of soluble interleukin-4 receptor and interleukin-5 antibody in preventing late-phase allergy-induced eustachian tube dysfunction","volume":"127","author":"Pollock","year":"2002","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/MLG.0b013e3181593deb","article-title":"Effects of ototopical antihistamine on otitis media in an allergic rat","volume":"118","author":"Cutler","year":"2008","journal-title":"Laryngoscope"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1177\/000348949910800605","article-title":"Efficacy of an Antiallergic Drug on Otitis Media with Effusion in Association with Allergic Rhinitis an Experimental Study","volume":"108","author":"Suzuki","year":"1999","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1001\/archotol.1958.00730020772013","article-title":"Secretory Otitis Media and Nasal Allergy Preliminary Report of Sixty-Six Patients Treated with Promethazine","volume":"68","author":"Weekes","year":"1958","journal-title":"AMA Arch. Otolaryngol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0165-5876(82)90076-3","article-title":"Elimination diets in the treatment of secretory otitis media","volume":"4","author":"Ruokonen","year":"1982","journal-title":"J. Pediatr. Otorhinolaryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.23822\/EurAnnACI.1764-1489.119","article-title":"Prevalence of allergic rhinitis in children with otitis media with effusion","volume":"52","author":"Norhafizah","year":"2020","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1288\/00005537-197504000-00019","article-title":"Allergic secretory otitis media: An approach to management","volume":"85","author":"Viscomi","year":"1975","journal-title":"Laryngoscope"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1177\/019459989010200607","article-title":"Allergy management of refractory serous otitis media","volume":"102","author":"Hurst","year":"1990","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00405-007-0563-y","article-title":"Antihistamine effects on experimental middle ear inflammatory model","volume":"265","author":"Chimona","year":"2008","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1159\/000236611","article-title":"Original Paper Treatment of Secretory Otitis Media with Local Instillation of Hydroxyzine","volume":"103","author":"Theoharides","year":"1994","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1017\/S0022215100147280","article-title":"Management of middle-ear effusions in children","volume":"98","author":"Hughes","year":"1984","journal-title":"J. Laryngol. Otol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1017\/S0022215100101124","article-title":"Efficacy of medical treatment as an adjunct to surgery in the treatment of secretory otitis media","volume":"100","author":"Lesser","year":"1986","journal-title":"J. Laryngol. Otol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1177\/00034894800890S367","article-title":"Diagnostic and Therapeutic Studies in Childhood Serous Otitis Media Results of Treatment with an Antihistamine-Adrenergic Combination","volume":"89","author":"Lancenbrunner","year":"1980","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_38","first-page":"CD003423","article-title":"Antihistamines and\/or decongestants for otitis media with effusion (OME) in children","volume":"9","author":"Griffin","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0385-8146(98)00075-3","article-title":"Clinical efficacy of an antiallergic drug on otitis media with effusion in association with allergic rhinitis","volume":"26","author":"Suzuki","year":"1999","journal-title":"Auris Nasus Larynx"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0165-5876(01)00613-9","article-title":"The role of laser assisted tympanostomy (LAT) in treating allergic children with chronic serous otitis media","volume":"62","author":"Prokopakis","year":"2002","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/01.mlg.0000246227.65877.1f","article-title":"Laser eustachian tuboplasty: Two-year results","volume":"117","author":"Poe","year":"2007","journal-title":"Laryngoscope"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.ijporl.2008.04.013","article-title":"Efficacy of allergy immunotherapy as a treatment for patients with chronic otitis media with effusion","volume":"72","author":"Hurst","year":"2008","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.anl.2018.07.011","article-title":"Clinical efficacy of anti-IL-5 monoclonal antibody mepolizumab in the treatment of eosinophilic otitis media","volume":"46","author":"Iino","year":"2019","journal-title":"Auris Nasus Larynx"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/MAO.0000000000003850","article-title":"Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy","volume":"44","author":"Ryder","year":"2023","journal-title":"Otol. Neurotol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S1081-1206(10)60967-2","article-title":"Effectiveness of instillation of triamcinolone acetonide into the middle ear for eosinophilic otitis media associated with bronchial asthma","volume":"97","author":"Iino","year":"2006","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/01.mao.0000224087.93096.4d","article-title":"Th1\/Th2 and Regulatory Cytokines in Adults with Otitis Media with Effusion","volume":"27","author":"Kariya","year":"2006","journal-title":"Otol. Neurotol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.anai.2014.04.021","article-title":"Antigen-Specific IgE in Middle Ear Effusion of Patients with Eosinophilic Otitis Media","volume":"113","author":"Kanazawa","year":"2014","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.otpol.2013.08.002","article-title":"Role of immunoglobulin e and gastro-esophageal reflux disease in the development of otitis media with effusion","volume":"68","author":"Gomaa","year":"2014","journal-title":"Otolaryngol. Pol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1097\/00005537-199609000-00017","article-title":"(1996). Association of Otitis Media with Efision and Allergy as Demonstrated by Intradermal Skin Testing and Eosinophil Cationic Protein Levels in Both Middle Ear Efisions and Mucosal Biopsies","volume":"106","author":"Hurst","year":"1996","journal-title":"Laryngoscope"},{"key":"ref_50","first-page":"454","article-title":"Increased nasal eosinophils in children with otitis media with effusion","volume":"115","author":"Caffarew","year":"1996","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0165-5876(02)00185-4","article-title":"Characterization of cytokines present in pediatric otitis media with effusion: Comparison of allergy positive and negative","volume":"66","author":"Jang","year":"2002","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1177\/019459989310800614","article-title":"The presence of eosinophil cationic protein in middle ear effusion","volume":"108","author":"Hurst","year":"1993","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0194-5998(99)70176-2","article-title":"Evidence of Possible Localized Specific Immunoglobulin E Production in Middle Ear Fluid as Demonstrated by ELISA Testing","volume":"121","author":"Hurst","year":"1999","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1067\/mhn.2000.109472","article-title":"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","volume":"123","author":"Wright","year":"2000","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00405-007-0373-2","article-title":"Cytokine levels in groups of patients with different duration of chronic secretory otitis","volume":"264","author":"Baljosevic","year":"2007","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.jaci.2004.07.061","article-title":"Similar allergic inflammation in the middle ear and the upper airway: Evidence linking otitis media with effusion to the united airways concept","volume":"114","author":"Nguyen","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/ajcp\/81.2.170","article-title":"Detection of Allergic Disease in Adenoid Tissue","volume":"81","author":"Loesel","year":"1984","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S315","DOI":"10.1016\/S0165-5876(99)00184-6","article-title":"Mast cells and tryptase in the middle ear of children with otitis media with effusion","volume":"49","author":"Hurst","year":"1999","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/S0165-5876(03)00223-4","article-title":"Expression of mast cell tryptase in pediatric otitis media with effusion","volume":"67","author":"Jang","year":"2003","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2310\/7070.2004.03073","article-title":"Evidence of allergic inflammation in the middle ear and nasopharynx in atopic children with otitis media with effusion","volume":"33","author":"Nguyen","year":"2004","journal-title":"J. Otolaryngol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1034\/j.1398-9995.2000.00289.x","article-title":"Evidence of Eosinophil, Neutrophil, and Mast-Cell Mediators in the Effusion of OME Patients with and Without Atopy","volume":"55","author":"Hurst","year":"2000","journal-title":"Allergy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.anl.2021.03.003","article-title":"Decreased miRNA-320e correlates with allergy in children with otitis media with effusion","volume":"48","author":"Adamczyk","year":"2021","journal-title":"Auris Nasus Larynx"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2147\/RMHP.S399499","article-title":"Analysis of Risk Factors for Otitis Media with Effusion in Children with Adenoid Hypertrophy","volume":"16","author":"Yang","year":"2023","journal-title":"Risk Manag. Healthc. Policy"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1067\/mai.2002.125697","article-title":"TH2 cytokine expression in atopic children with otitis media with effusion","volume":"110","author":"Sobol","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0165-5876(03)00015-6","article-title":"Demonstration of RANTES and Eosinophilic Cataionic Protein in Otitis Media with Effusion with Allergy","volume":"67","author":"Jang","year":"2003","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1111\/j.1365-2222.2012.04038.x","article-title":"Allergic rhinitis is associated with otitis media with effusion: A birth cohort study","volume":"42","author":"Chawes","year":"2012","journal-title":"Clin. Exp. Allergy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1055\/s-2007-998317","article-title":"Middle ear effusion and allergy in childhood","volume":"68","author":"Bachert","year":"1989","journal-title":"Laryngo-Rhino-Otologie"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/archotol.128.5.561","article-title":"The impact of atopy on neutrophil activity in middle ear effusion from children and adults with chronic otitis media","volume":"128","author":"Hurst","year":"2002","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.ijporl.2009.04.024","article-title":"Expression of GATA3, T-bet, IL-4, and IFN-\u03b3 mRNA in the Effusion of OME Patients","volume":"73","author":"Shim","year":"2009","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ijporl.2016.09.025","article-title":"Increased IL-17 and 22 mRNA Expression in Pediatric Patients with Otitis Media with Effusion","volume":"90","author":"Kwon","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1177\/00034894760850S222","article-title":"Immunoglobulin E in Chronic Middle Ear Effusions","volume":"85","author":"Lim","year":"1976","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1177\/000348947808700209","article-title":"Immunoglobulin E in Chronic Middle Ear Effusions Comparison of Rist, Prist, and Ria Techniques","volume":"87","author":"Lewis","year":"1978","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3109\/00016488409122890","article-title":"Atopic allergy and otitis media with effusion","volume":"98","author":"Boedts","year":"1984","journal-title":"Acta Otolaryngol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.anl.2009.05.002","article-title":"Prevalence and risk factors for persistent otitis media with effusion in primary school children in Istanbul, Turkey","volume":"37","author":"Gultekin","year":"2010","journal-title":"Auris Nasus Larynx"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0165-5876(98)00002-0","article-title":"The Point Prevalence of Otitis Media with Effusion Among School Children in Greece","volume":"44","author":"Apostolopoulos","year":"1998","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1046\/j.1365-2222.1998.00284.x","article-title":"Atopy in children with otitis media with effusion","volume":"28","author":"Caffarelli","year":"1998","journal-title":"Clin. Exp. Allergy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s00405-010-1297-9","article-title":"The role of atopy in otitis media with effusion among primary school children: Audiological investigation","volume":"267","author":"Martines","year":"2010","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"133","DOI":"10.14639\/0392-100X-2456","article-title":"Risk factors for otitis media with effusion in children with adenoid hypertrophy","volume":"40","author":"Songu","year":"2020","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1258\/0022215011909422","article-title":"Main Articles Adult-Onset Otitis Media with Effusion: Results Following Ventilation Tube Insertion","volume":"115","author":"Yung","year":"2001","journal-title":"J. Laryngol. Otol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/00034894941030S505","article-title":"The Role of IgE-Mediated Hypersensitivity in Otitis Media with Effusion","volume":"103","author":"Corey","year":"1994","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.ijporl.2010.03.023","article-title":"Risk Factors for Otitis Media Among Preschool, Rural Indian Children","volume":"74","author":"Sophia","year":"2010","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1067\/mhn.2003.53","article-title":"The role of rhinitis in chronic otitis media","volume":"128","author":"Mion","year":"2003","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0165-5876(93)90191-5","article-title":"Middle ear diseases in relation to atopy and nasal metachromatic cells in infancy","volume":"26","author":"Irander","year":"1993","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"110647","DOI":"10.1016\/j.ijporl.2021.110647","article-title":"Prevalence of and Factors Affecting Otitis Media with Effusion in Children in the Region from Balkans to Caspian Basin; A Multicentric Cross-Sectional Study","volume":"143","author":"Kalcioglu","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ijporl.2016.03.008","article-title":"Prevalence of otitis media with effusion in children with allergic rhinitis, a cross sectional study","volume":"84","author":"Pau","year":"2016","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.ijporl.2011.01.031","article-title":"Risk Factors for Otitis Media with Effusion: Case-Control Study in Sicilian Schoolchildren","volume":"75","author":"Martines","year":"2011","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.otohns.2004.02.003","article-title":"The role of food allergy in otitis media with effusion","volume":"130","author":"Altintas","year":"2004","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_88","first-page":"995","article-title":"A Survey of Hearing Loss in Vancouver School Children: Part II. The Association Between Secretory Otitis Media and Enlarged Adenoids, Infection and Nasal Allergy Season of Screening","volume":"98","author":"Murray","year":"1968","journal-title":"Can. Med. Assoc. J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1017\/S0022215100090356","article-title":"Secretory Otitis Media-A Retrospective General Practice Survey","volume":"95","author":"Schutte","year":"1981","journal-title":"J. Laryngol. Otol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Torretta, S., Pignataro, L., Carioli, D., Ibba, T., Folino, F., Rosazza, C., Fattizzo, M., and Marchisio, P. (2018). Phenotype profiling and allergy in otitis-prone children. Front. Pediatr., 6.","DOI":"10.3389\/fped.2018.00383"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4103\/jwas.jwas_107_22","article-title":"Prevalence and co-morbidities of adult-onset otitis media with effusion","volume":"12","author":"Sogebi","year":"2022","journal-title":"J. West Afr. Coll. Surg."},{"key":"ref_92","first-page":"209","article-title":"Correlation between Allergic Rhinitis and Otitis Media with Effusion","volume":"31","author":"Sharifian","year":"2019","journal-title":"Iran. J. Otorhinolaryngol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/j.1398-9995.2006.00971.x","article-title":"IgE sensitization, respiratory allergy symptoms, and heritability independently increase the risk of otitis media with effusion","volume":"61","author":"Chantzi","year":"2006","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ijporl.2012.09.039","article-title":"Allergic diseases in children with otitis media with effusion","volume":"77","author":"Kwon","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1177\/019459988509300508","article-title":"Further Observations on the Role of IgE-Mediated Hypersensitivity in Recurrent Otitis Media with Effusion","volume":"93","author":"Bernstein","year":"1985","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/lary.25682","article-title":"Age: An Effect Modifier of the Association Between Allergic Rhinitis and Otitis Media with Effusion","volume":"126","author":"Roditi","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e39671","DOI":"10.1097\/MD.0000000000039671","article-title":"Causal relationship between allergic rhinitis and otitis media: A Mendelian randomization study","volume":"103","author":"Wang","year":"2024","journal-title":"Medicine"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1398-9995.1981.tb01825.x","article-title":"Secretory Otitis Media and Allergy with Special Reference to the Cytotoxic Leucocyte Test","volume":"36","author":"Ruokonen","year":"1981","journal-title":"Allergy"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.otohns.2009.03.007","article-title":"The prevalence of atopic symptoms in children with otitis media with effusion","volume":"141","author":"Souter","year":"2009","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0165-5876(97)00049-9","article-title":"Prevalence of otitis media with effusion amongst pre-school children in Malaysia","volume":"41","author":"Saim","year":"1997","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1749-4486.2006.01154.x","article-title":"Total Serum IgE and IgE Antibodies Specific to House Dust Mite Found in Two Aged-Matched Cohorts of Children with and Without Otitis Media with Effusion","volume":"31","author":"Coulson","year":"2006","journal-title":"Clin. Otolaryngol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.ijporl.2013.09.017","article-title":"A study of the role of different forms of chronic rhinitis in the development of otitis media with effusion in children affected by adenoid hypertrophy","volume":"77","author":"Quaranta","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_103","first-page":"148","article-title":"The role of allergic rhinitis in the development of otitis media with effusion: Effect on eustachian tube function","volume":"28","author":"Yeo","year":"2007","journal-title":"Am. J. Otolaryngol. Head Neck Med. Surg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/j.ijporl.2005.03.047","article-title":"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","volume":"69","author":"Xenellis","year":"2005","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00405-010-1290-3","article-title":"Allergic rhinitis and chronic suppurative otitis media","volume":"268","author":"Bakhshaee","year":"2011","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e065291","DOI":"10.1136\/bmjopen-2022-065291","article-title":"Factors affecting the occurrence of otitis media with effusion in preschool and elementary school children: A comparative cross-sectional study","volume":"12","author":"Restuti","year":"2022","journal-title":"BMJ Open"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1001\/archotol.1979.00790220016004","article-title":"Etiologic Factors in Secretory Otitis","volume":"105","author":"Tos","year":"1979","journal-title":"Arch. Otolaryngol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1365-2273.1979.tb01899.x","article-title":"The occurrence of secretory otitis media in allergic children","volume":"4","author":"Rahko","year":"1979","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2500\/108854189778961071","article-title":"Eustachian Tube Dysfunction in Children with Ragweed Hayfever During Natural Pollen Exposure","volume":"10","author":"Osur","year":"1989","journal-title":"Allergy Asthma Proc."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Hellings, P.W., and Prokopakis, E.P. (2010). Global airway disease beyond allergy. arXiv.","DOI":"10.1007\/s11882-010-0107-1"},{"key":"ref_111","first-page":"S1","article-title":"Clinical Practice Guideline","volume":"154","author":"Rosenfeld","year":"2016","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Klimek, L., Brough, H.A., Arasi, S., Toppila-Salmi, S., Bergmann, C., Jutel, M., Bousquet, J., Hox, V., Gevaert, P., and Tomazic, P.V. (2025). Otitis Media with Effusion (OME) and Eustachian Tube Dysfunction: The Role of Allergy and Immunity\u2014An EAACI Position Paper. Allergy.","DOI":"10.1111\/all.16554"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Yu, X., Zhang, H., Zong, S., and Xiao, H. (2024). Allergy in Pathogenesis of Eustachian Tube Dysfunction. arXiv.","DOI":"10.1016\/j.waojou.2023.100860"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1177\/0194599820987458","article-title":"Effects of COVID-19 Lockdown on Otitis Media with Effusion in Children: Future Therapeutic Implications","volume":"165","author":"Marchisio","year":"2021","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e03853-23","DOI":"10.1128\/spectrum.03853-23","article-title":"Characteristics of upper respiratory tract rhinovirus in children with allergic rhinitis and its role in disease severity","volume":"12","author":"Gao","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Chen, J.R., Liu, X., Liu, Z., Zhou, Y., Xie, L., Zhang, J., Tan, J., Yang, Y., Tian, M., and Dong, Y. (2023). Early exposure to infections increases the risk of allergic rhinitis\u2014A systematic review and meta-analysis. BMC Pediatr.","DOI":"10.1186\/s12887-023-03870-0"},{"key":"ref_117","first-page":"1053","article-title":"Pidotimod as add-on therapy in patients with pollen-induced allergic rhinitis and asthma and associated respiratory infections","volume":"35","author":"Marogna","year":"2021","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13052-020-00859-8","article-title":"Efficacy of Pidotimod Use in Treating Allergic Rhinitis in a Pediatric Population","volume":"46","author":"Brindisi","year":"2020","journal-title":"Ital. J. Pediatr."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Choulakis, K., Karatzanis, A., Skoulakis, C., Vlastos, I.M., and Prokopakis, E. (2025). Traditional herbal medicine in the treatment of acute and chronic rhinosinusitis: A systematic review. Rhinology.","DOI":"10.4193\/Rhin23.526"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/11\/805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:43:41Z","timestamp":1760031821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/11\/805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":119,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cells14110805"],"URL":"https:\/\/doi.org\/10.3390\/cells14110805","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]}}}