Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium

Objectives Examine bronchial epithelium-derived gene expression signature of bronchiectasis (BE) in nasal epithelium. Methods We studied 220 participants from the Detection of Early Lung Cancer Among Military Personnel study with bulk RNA-seq of nasal epithelium brushings. Gene set enrichment analysis (GSEA) examined whether genes previously identified as increased or decreased in bronchial epithelium of individuals with radiologic BE are enriched among genes most altered in nasal epithelium. GSEA and cell-type specific signatures assessed changes in nasal epithelium cellular composition associated with radiologic BE. Results No genes were significantly differentially expressed in nasal epithelium between participants with and without widespread radiologic BE. However, genes previously found altered in bronchial epithelium are concordantly enriched among genes most increased or decreased in nasal epithelium (p=3×10 −7 , increased; p=6×10 −8 , decreased). GSEA using cell-type signatures shows BE in nasal epithelium is associated with increased multiciliated and deuterosomal cell-related gene expression and decreased basal cell-related gene expression, consistent with bronchial findings. Conclusion This work validates our bronchial BE signature in an independent dataset and demonstrates that gene expression changes associated with radiologic BE in nasal epithelium are concordant but reduced in magnitude compared with bronchial epithelium. These findings support considering nasal brushings as a less invasive tool for BE screening and monitoring.