Association of Gel-Forming Mucins and Aquaporin Gene Expression With Hearing Loss, Effusion Viscosity, and Inflammation in Otitis Media With Effusion
| Autor: | Justin C. Yan, Joseph E. Kerschner, Pawjai Khampang, Tina L. Samuels, Wenzhou Hong, Robert H. Chun, Alexander C. Mackinnon, Michael E. McCormick, Nikki Johnston, Blake C. Papsin, Peter W. Dettmar |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Down syndrome medicine.medical_specialty Hearing loss Biopsy medicine.medical_treatment Gene Expression Gastroenterology 03 medical and health sciences Internal medicine otorhinolaryngologic diseases medicine Humans Tympanostomy tube Child Hearing Loss Original Investigation Otitis Media with Effusion Viscosity business.industry Infant Cholesteatoma Odds ratio medicine.disease Middle Ear Ventilation Mucin-5B Aquaporin 5 Conductive hearing loss Surgery 030104 developmental biology Otitis Otorhinolaryngology Effusion Case-Control Studies Child Preschool Female medicine.symptom business Gels |
| Zdroj: | JAMA Otolaryngology–Head & Neck Surgery. 143:810 |
| ISSN: | 2168-6181 |
| Popis: | Persistent, viscous middle ear effusion in pediatric otitis media (OM) contributes to increased likelihood of anesthesia and surgery, conductive hearing loss, and subsequent developmental delays. Biomarkers of effusion viscosity and hearing loss have not yet been identified despite the potential that such markers hold for targeted therapy and screening.To investigate the association of gel-forming mucins and aquaporin 5 (AQP5) gene expression with inflammation, effusion viscosity, and hearing loss in pediatric OM with effusion (OME).Case-control study of 31 pediatric patients (aged 6 months to 12 years) with OME undergoing tympanostomy tube placement and control individuals (aged 1 to 10 years) undergoing surgery for cochlear implantation from February 1, 2013, through November 30, 2014. Those with 1 or more episodes of OM in the previous 12 months, immunologic abnormality, anatomical or physiologic ear defect, OM-associated syndrome (ie, Down syndrome, cleft palate), chronic mastoiditis, or history of cholesteatoma were excluded from the study. All patients with OME and 1 control were recruited from Children's Hospital of Wisconsin, Milwaukee. The remainder of the controls were recruited from Sick Kids Hospital in Toronto, Ontario, Canada.Two to 3 middle ear biopsy specimens, effusions, and preoperative audiometric data (obtained3 weeks before surgery) were collected from patients; only biopsy specimens were collected from controls. Expression of the mucin 2 (MUC2), mucin 5AC (MUC5AC), mucin 5B (MUC5B), and AQP5 genes were assayed in middle ear biopsy specimens by quantitative polymerase chain reaction. One middle ear biopsy specimen was sectioned for histopathologic analysis. Reduced specific viscosity of effusions was assayed using rheometry.Of the 31 study participants, 24 patients had OME (mean [SD] age, 50.4 [31.9] months; 15 [62.5%] male; 16 [66.7%] white) and 7 acted as controls (mean [SD] age, 32.6 [24.4] months; 2 [26.6%] male; 6 [85.7%] white). Mucins and AQP5 gene expression were significantly higher in patients with OME relative to controls (MUC2: ratio, 127.6 [95% CI, 33.7-482.7]; MUC5AC: ratio, 3748.8 [95% CI, 558.1-25 178.4]; MUC5B: ratio, 471.1 [95% CI, 130.7-1697.4]; AQP5: ratio, 2.4 [95% CI, 1.1-5.6]). A 2-fold increase in MUC5B correlated with increased hearing loss (air-bone gap: 7.45 dB [95% CI, 2.65-12.24 dB]; sound field: 6.66 dB [95% CI, 6.63-6.69 dB]), effusion viscosity (2.75 mL/mg; 95% CI, 0.89-4.62 mL/mg), middle ear epithelial thickness (3.5 μm; 95% CI, 1.96-5.13 μm), and neutrophil infiltration (odds ratio, 1.7; 95% CI, 1.07-2.72). A 2-fold increase in AQP5 correlated with increased effusion viscosity (1.94 mL/mg; 95% CI, 0.08-3.80 mL/mg).Further exploration of the role of MUC5B in the pathophysiology of OME holds promise for development of novel, targeted therapies to reduce effusion viscosity, facilitation of effusion clearance, and prevention of disease chronicity and hearing loss in patients with OME. |
| Databáze: | OpenAIRE |
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