Transcriptomic signatures convergent across multiple studies of upper and lower airway allergic disease support the unified airway hypothesis (HUM7P.321)

Abstract

Abstract Asthma is frequently associated with co-morbid diseases of the upper airways, including chronic rhinosinusitis (CRS). This has led to a hypothesis that the upper and lower airway may be immunologically linked, functioning as a continuous mucosal epithelial barrier interacting with the environment. Despite a growing number of transcriptomics studies, the differences and similarities between upper and lower airways in allergic disease are still poorly understood. We analyzed raw microarray data from three independent studies of CRS and four studies of asthma, and conducted a secondary multivariate and pathway analysis to identify genes commonly altered in both diseases. Despite regional differences, close to 20% of genes found to be differentially expressed in CRS were also found to be differentially expressed in the lower airways of asthmatics. Notable examples are IL6R, IL13RA2, MSMB, MUC5B, POSTN, SERPINB2, TFF2, WIF1 and WNT5A. Pathway analysis revealed that key processes represented by these shared genes are developmental pathway signaling, epithelial-mesenchymal transition and innate immune response, suggesting co-existence of epithelial remodeling and persistence of innate immune signals. Interestingly, many of the genes altered in CRS that we identified in the upper airways are also asthma susceptible genes previously identified through GWAS studies (e.g., IL1RL1, ORMDL3), indicating a common role for these genes in the pathogenesis of respiratory allergic diseases.