Nasal sampling identifies disease-relevant signals in a real-world airways disease cohort

<bold>Background:</bold> Lower airways sampling, as a target to evaluate asthma and COPD biology, is invasive and resource intensive. The one airway hypothesis proposes that the upper airways exist in a continuum with the lower airways, such that the nose reflects disease-relevant biology. <bold>Aim:</bold> To evaluate gene and protein expression in the nasal epithelium and nasal lining fluid (NLF) of patients with airway disease from a sub-study of NOVELTY (<ext-link>NCT02760329</ext-link>) and compare with established lower airway findings. <bold>Methods:</bold> Following nasal sampling, brushings and NLF (eluted from nasosorption strips) were profiled by RNAseq and Olink Explore 3072, respectively, and differential expression analysis was performed by DESeq2 and OlinkAnalyze, respectively. <bold>Results:</bold> Nasal samples were collected from 245 patients (122 with physician-assigned asthma). Good quality gene and protein expression data were obtained from 95% of brush and 99% of NLF samples. Differential expression analysis in patients with asthma, stratified by FeNO at the time of nasal sampling, identified 25 downregulated and 62 upregulated genes, overlapping known lower airway T2 genes (Figure). <bold>Conclusion:</bold> High quality RNAseq and Olink data reflecting airways disease-relevant biology were generated in nasal samples from NOVELTY. Further analysis will inform the ambition to introduce minimally invasive nasal sampling into clinical practice to enable precision medicine. <fig><object-id>erj;64/suppl_68/OA3764/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>