Late Breaking Abstract - Nasal transcriptomic profiling of children with severe childhood asthma reveals distinct molecular subgroups related to epithelial function

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# shared last authors Severe asthma in children is difficult to manage due to its clinical and biological heterogeneity. Since nasal transcriptomic profiles can mirror lower airway inflammation, this study explores their potential as a non-invasive approach to identify molecular subgroups. Nasal brushing samples were collected at baseline from children with severe asthma (GINA step ≥3) recruited in two Dutch hospitals, as part of the PANDA cohort. Bulk RNA-sequencing data from nasal brushings were normalized and analyzed. Principal component analysis and hierarchical clustering was used to identify distinct transcriptomic clusters. Differential gene expression analysis was performed, followed by gene set enrichment analysis (GSEA) with Gene Ontology, biological patways database. We investigated 35 children (mean age 12.4 ± 3.3 years, 60% boys). Unsupervised clustering identified 2 different molecular subgroups. The smallest cluster (n=4) was characterized by upregulation of genes linked to airway inflammation and epithelial remodeling (e.g. IL18, EDN1, ISG15), and downregulation of genes suggesting impaired mucociliary function (SCIN, ST6GAL1). In addition, these patients showed enrichment in gene expression profiles related to cilium movement and fluid transport, while pathways associated with keratinocyte differentiation and keratinization were downregulated, suggesting altered epithelial function. These findings support nasal transcriptomics as a non-invasive tool to explore molecular heterogeneity in pediatric severe asthma and highlight its potential for biomarker discovery and personalized treatment.

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