Metabolomic Profiling of Middle Ear Effusion Suggests a Predominant Influence of Age over Viscosity: An HR-MAS NMR Study

Otitis media with effusion (OME) involves heterogeneous middle ear effusion (MEE), and its classification based on viscosity (serous/mucous) is often confounded by patient age. This study determined the independent contributions of age and viscosity to the MEE metabolome. In this prospective study, high-resolution magic-angle spinning nuclear magnetic resonance analysis of 83 MEE samples (45 adult serous, 17 child serous < 12 years, and 21 child mucous) was performed. Statistical analyses included principal component analysis, correlation analysis, analysis of covariance (ANCOVA), and age-adjusted receiver operating characteristic curve analysis. Age was the primary metabolic variance determinant, overshadowing viscosity-related differences. Significant age-associated metabolic trends were identified: pyruvate and lactate levels increased with age, whereas glutamate and leucine levels decreased, indicating energy and inflammatory metabolism shifts. After adjusting for age using ANCOVA, taurine, glycine, and choline were significantly associated with effusion viscosity, and a combined panel of these metabolites achieved an age-adjusted area under the curve of 0.707 (95% confidence interval: 0.55-0.89). In conclusion, the MEE metabolic profile was more strongly influenced by patient age than by viscosity, suggesting fundamental differences in OME pathophysiology between children and adults. Nonetheless, specific viscosity-associated metabolites were identified, offering a basis for objective metabolic typing.