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Association of Gel-Forming Mucins and Aquaporin Gene Expression With Hearing Loss, Effusion Viscosity, and Inflammation in Otitis Media With Effusion. JAMA Otolaryngol Head Neck Surg 2017 08 01;143(8):810-817

Date

06/09/2017

Pubmed ID

28594978

Pubmed Central ID

PMC5710562

DOI

10.1001/jamaoto.2017.0386

Scopus ID

2-s2.0-85027729929   9 Citations

Abstract

Importance: 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.

Objective: 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).

Design, Setting, and Participants: 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.

Main Outcomes and Measures: Two to 3 middle ear biopsy specimens, effusions, and preoperative audiometric data (obtained <3 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.

Results: 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).

Conclusions and Relevance: 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.

Author List

Samuels TL, Yan JC, Khampang P, Dettmar PW, MacKinnon A, Hong W, Johnston N, Papsin BC, Chun RH, McCormick ME, Kerschner JE

Authors

Robert H. Chun MD Associate Professor in the Otolaryngology department at Medical College of Wisconsin
Wenzhou Hong DVM, PhD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin
Nikki Johnston PhD Associate Professor in the Otolaryngology department at Medical College of Wisconsin
Michael E. McCormick MD Associate Professor in the Otolaryngology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aquaporin 5
Biopsy
Case-Control Studies
Child
Child, Preschool
Female
Gels
Gene Expression
Hearing Loss
Humans
Infant
Male
Middle Ear Ventilation
Mucin-5B
Otitis Media with Effusion
Viscosity
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280