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Abstract
Chronic otitis media with effusion (COME) is the most common cause of childhood hearing loss in the developed world. Underlying pathophysiology is not well understood, and in particular the factors that lead to the transition from acute to chronic inflammation. Here we present the first genome-wide transcript analysis of white blood cells in the effusion of children with COME. Analysis of microarray data for enriched pathways reveals upregulation of hypoxia pathways, which is confirmed using real-time PCR and determining VEGF protein titres. Other pathways upregulated in both mucoid and serous effusions include Toll-like receptor signaling, complement, and RANK-RANKL. Cytology reveals neutrophils and macrophages predominated in both serous and mucoid effusions, however, serous samples had higher lymphocyte and eosinophil differential counts, while mucoid samples had higher neutrophil differential counts. Transcript analysis indicates serous fluids have CD4+ and CD8+ T-lymphocyte, and NK cell signatures. Overall, our findings suggest that inflammation and hypoxia pathways are important in the pathology of COME, and targets for potential therapeutic intervention, and that mucoid and serous COME may represent different immunological responses.
Highlights
Otitis media with effusion (OME) or “glue ear” is the most common cause of hearing loss in children in a developed world environment
The pathophysiology underlying OME is not fully understood. It often follows an episode of acute otitis media (AOM), where ascent of bacteria from the nasopharynx leads to a purulent effusion in the middle ear
We report that microarray analysis of effusions showed upregulation of hypoxia signaling, response to hypoxia, TollLike Receptor signaling, the complement and the RANKRANKL pathways
Summary
Otitis media with effusion (OME) or “glue ear” is the most common cause of hearing loss in children in a developed world environment. The disease is characterized by an inflammatory effusion that prevents transmission of sound through the middle ear space, and if chronic (chronic OME, COME) is associated with potential effects on language acquisition and learning. The pathophysiology underlying OME is not fully understood. It often follows an episode of acute otitis media (AOM), where ascent of bacteria from the nasopharynx leads to a purulent effusion in the middle ear. As this purulent effusion resolves, the serous or mucoid effusion of OME replaces it. COME affects 5–6% of all children in their second year of life (Bhutta, 2014), and if associated with hearing disability may be treated with the surgical insertion of grommets (ventilation tubes) which eliminate the effusion
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