Altered airway epithelial cell landscape in U-BIOPRED severe asthma

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The airway epithelial cell landscape has been defined in mild-moderate asthma (MMA) but not in patients with severe asthma (SA). To examine whether cellular deconvolution using single cell (sc) signatures derived from MMA bronchial biopsies can differentiate SA in the U-BIOPRED cohort. Gene set variation analysis (GSVA) gave enrichment scores (ES) for 12 scRNA-seq cell signatures in transcriptomic data from bronchial brushings of 36 MMA, 103 SA and 44 healthy control (HC) subjects. Overlapping genes between cell signatures were removed. The ES of basal, suprabasal and secretory cell signatures were significantly decreased in SA and MMA compared to HC (adj p<0.05)(Figure). The ES of goblet, serous and PNEC cell, ionocyte and pericyte signatures were significantly higher in SA compared to HC (adj p<0.05)(Figure). Asthma severity did not affect the ES of brush, deuterosomal, precursor or mucociliated N cells. T2high asthmatics had a greater ES for goblet, brush, serous and precursor cell, ionocyte and pericyte signatures compared to T2low subjects (adj p<0.05). Deuterosomal and mucociliated N cell signature ES were significantly reduced in T2high vs T2low asthmatics. Some differences only occurred in MMA or SA groups. Current smokers had a significant enrichment of goblet, PNEC and brush cell signatures compared to ex-smokers (adj p<0.05). There is an altered airway epithelial cell landscape in SA that is modified by smoking and T2 biology.