Serum Midkine as a Potential Biomarker Associated with Disease Severity and Remodeling-Related Mediators in Children with Asthma

Introduction: Asthma is a heterogeneous inflammatory airway disease in children, for which reliable circulating biomarkers reflecting disease severity and remodeling-associated inflammation remain limited. Midkine, a heparin-binding growth factor involved in inflammatory and fibrotic processes, has emerged as a potential biomarker; however, its clinical relevance in pediatric asthma remains unclear. This study aimed to investigate the association between serum midkine levels and disease severity in children with asthma. Methods: We enrolled 109 children with asthma (classified into mild, moderate, and severe groups) and 110 healthy controls. Children with asthma were classified into mild, moderate, and severe groups according to the Global Initiative for Asthma (GINA) criteria, and serum midkine levels were measured by ELISA, along with clinical and lung function assessments. Results: Serum midkine levels were significantly higher in children with asthma than in healthy controls and increased progressively with disease severity. Receiver operating characteristic analysis demonstrated good diagnostic performance of serum midkine for asthma (AUC = 0.949), with a sensitivity of 87.2% and specificity of 94.5% at a cutoff value of 948 pg/mL. Additionally, serum midkine levels were negatively correlated with lung function parameters (FEV1, FEV1/FVC, and PEF) and positively correlated with eosinophilia, total immunoglobulin E (IgE), fractional exhaled nitric oxide (FeNO), pro-inflammatory cytokines, and remodeling-related mediators. Conclusion: These findings highlight midkine as a promising biomarker and potential therapeutic target for asthma.