Background and aim:
Despite the effectiveness of ventilation tube insertion (VTI/grommets) in restoring otitis media associated hearing loss, between 20-50% of children require repeat surgery for recurrent disease. This contributes to excessive wait-lists and increased disease sequelae. Disease recurrence is largely due to bacterial persistence within biofilms forming infectious reservoirs. Treatments that target the biofilm, as well as identification of other modifiable risk factors associated with repeat surgery, are required to prevent recurrent disease and improve outcomes. This study trialled the safety and efficacy of human recombinant DNAse I (Dornase alfa) to target bacterial persistence in the ear. Any predictors of the need for repeat surgery were also assessed.
Research method:
Children with bilateral otitis media were recruited prior to their first VTI surgery. During surgery, middle ear effusions (MEE) were collected, then Dornase alfa was applied into one ear and saline (placebo) into the other. Children were followed intensely for 2 years. MEE were analysed for otopathogens using qPCR, cytokines using multiplexed immunoassay, and metabolites using gas chromatography and mass spectrometry.
Results:
Sixty children (mean age 2.3 years) were recruited with 14 (23%) requiring repeat VTI within 2 years. Dornase alfa was safe and well-tolerated. There was a trend for slower blockage and/or extrusion of grommets in ears treated with Dornase alfa. Presence of Haemophilus influenzae (64% vs 15%; p<0.001), elevated inflammation (IL-1β, IL-6, IL-8 and IL-10; p≤0.004) and up to 12-fold increases in 9 metabolites, including cholesterol and Myo-inositol (p≤0.026), were higher in MEE from children requiring repeat surgery.
Conclusion:
Dornase alfa application into the middle ear is safe, well-tolerated and may prolong grommet effectiveness. Multiple treatment applications are likely to be required. Biomarkers associated with an increased risk for repeat VTI surgery indicate ongoing infection and inflammation at the time of surgery. These biomarkers represent treatable targets to reduce the repeat surgeries. These findings are being validated in a larger cohort with multiple Dornase alfa applications.