Nasal transcriptomic profiling reveals distinct patterns in Type 2 Asthma

Asthma is a heterogeneous major chronic respiratory disease that is commonly characterized as type-2 (T2) and non-type-2 (NT2); however, the underlying mechanisms are not fully understood. Therefore, we investigated nasal transcription using RNA-seq profiles in relation to T2 signatures among subjects with or without asthma. The T2 signature included at least two of the following: FeNO ≥25 ppb, blood eosinophils ≥0.3x10⁹/L, and IgE-sensitization. Asthma was defined by diagnosis and symptoms and/or treatment. Nasal brush RNA-sequencing using the NovaSeq 6000 platform was performed on 517 subjects (aged 22-24 years) from the Swedish BAMSE cohort, comprising NT2 control (non-asthma, n=342), NT2 asthma (n=29), T2 asthma (n=21), and T2 control (non-asthma, n=63). The limma R package was used for differential expression analysis after adjustment for covariates and cell type, while accounting for the false discovery rate. Forty-eight and 46 genes were differentially expressed in association with T2 asthma and T2 control compared to NT2 control, respectively. Fourteen genes overlapped, with Cystatin SN (CST1) being the most significantly associated. Periostin (POSTN) (LogFC=1.58, p=1.14x10⁻⁷) and 15-lipoxygenase (ALOX15) (LogFC=0.67, p=1.02x10⁻⁶) were among the top distinct differentially expressed genes in T2 asthma. NT2 asthma showed no differential gene expression. Gene Ontology biological processes analysis highlighted nitrogen regulation, metabolic processes, and proteolysis as enriched in T2 asthma. In conclusion, T2 asthma and T2 non-asthma controls displayed both distinct and shared gene expression patterns. CST1, POSTN and ALOX15 are promising biomarkers for gaining further knowledge on T2 asthma mechanisms.