Independent Associations Between Arginine-Related Metabolites and Disease Activity in Pediatric Asthma: A Multivariable Biomarker Study

Abstract

Asthma is a heterogeneous inflammatory airway disease with variable clinical phenotypes. Dysregulation of the arginine-nitric oxide (NO) pathway contributes to airway hyperresponsiveness and endothelial dysfunction, but its role across stages of pediatric asthma remains unclear. In order to replicate real-world clinical heterogeneity, this investigation assessed serum levels of L-arginine, symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA), L-citrulline, and the SDMA/ADMA ratio in children with managed asthma, asthma exacerbation, upper respiratory tract infections (URTIs), pneumonia, COVID-19, and healthy controls. Discovering stage-specific arginine pathway changes and evaluating their ability to distinguish asthma and asthma exacerbations from other clinically similar respiratory disorders was the primary aim of our research study. Receiver operating characteristic (ROC) analysis demonstrated that the SDMA/ADMA ratio achieved the strongest individual discriminative performance for distinguishing asthma exacerbation from controlled asthma (AUC: 0.917), while the combined multimarker model incorporating all four metabolites yielded an AUC of 0.983 with a sensitivity of 87.5% and specificity of 95.5%. These results indicate that arginine pathway metabolites, especially the SDMA/ADMA ratio, may merit additional research as possible markers of acute disease activity in asthma, even though they are exploratory and need external confirmation.