GSE118761
RNA-sequencing of ex vivo nasal and tracheal epithelial cells from a paediatric cohort including non-atopic non-wheezers, atopic non-wheezers, atopic wheezers, and non-atopic wheezers
Rationale: Emerging evidence suggests that disease vulnerability is expressed throughout the airways; the so-called “unified airway hypothesis” but the evidence to support this is predominantly indirect. Objectives: To establish the transcriptomic profiles of the upper and lower airway and determine their level of similarity irrespective of airway symptoms (wheeze) and allergy. Methods: We performed RNA-sequencing on upper and lower airway epithelial cells from 63 children with or without wheeze and accompanying atopy, utilizing differential gene expression and gene co-expression analyses to determine transcriptional similarity. Results: We observed ~91% homology in the expressed between the two sites. When co-expressed genes were grouped into modules relating to biological functions, all were found to be conserved between the two regions, resulting in a consensus network containing 16 modules associated with ribosomal function, metabolism, gene expression, mitochondrial activity and anti-viral responses through interferon activity. Although symptom associated gene expression changes were more prominent in the lower airway, they were reflected in nasal epithelium and included; IL1RL1, PTGS1, CCL26 and POSTN. Through network analysis we identified a cluster of co-expressed genes associated with atopic-wheeze in the lower airway, which could equally distinguish atopic and non-atopic phenotypes in upper airway samples. Conclusions: We show that the upper and lower airway are significantly conserved in their transcriptional composition, and that variations associated with disease are present in both nasal and tracheal epithelium. Clinical Implication: Findings from this study supporting a unified airway imply that clinical insight regarding the lower airway in health and disease can be gained from studying the nasal epithelium. Overall design: Four participant groups; non-atopic non-wheezers, atopic wheezers, atopic non-wheezersand non-atopic wheezers - paired nasal and bronchial brushing samples for most participants. Matching replicate numbers indicate paired samples unless otherwise specified.