Metabolomics discover distinct metabolite profiles in children with different airway allergic diseases

Allergic rhinitis (AR), asthma, and their combined allergic rhinitis and asthma syndrome (CARAS) frequently coexist. However, the underlying pathophysiological and metabolic mechanisms, as well as reliable diagnostic differentiation, remain challenging. Carboxyl-containing metabolites (CCMs) have been implicated in the pathogenesis of these conditions; therefore, this study aimed to comprehensively profile serum CCMs in pediatric patients. Sera from 63 children with AR, 41 with asthma, and 90 with CARAS, sensitized to Dermatophagoides farina and/or Dermatophagoides pteronyssinus, were analyzed using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry coupled with 5-(diisopropylamino) amylamine derivatization. The results identified 100 differentially expressed metabolites common across them, alongside disease-specific alterations of 23, 17, and 31 unique to AR, asthma, and CARAS, respectively. These findings reveal that allergic airway diseases share a core metabolic disturbances that may reflect immune dysregulation and potentially involve gut dysbiosis, and yet exhibit distinct profiles: AR shows localized amino acid perturbations, asthma displays systemic lipid remodeling, and CARAS manifests as a distinct comorbid phenotype combining both features.