Affleck, Karen, Taylor, Adam, Riley, John H., Pavlidis, Stelios, Fleming, Louise, Adcock, Ian, Auffray, Charles, Bigler, Jeanette, Bisgaard, Hans, Boedigheimer, Michael, Bonnelykke, Klaus, Bush, Andrew, Chung, K. Fan, Djukanovic, Ratko, Frey, Urs, Fowler, Stephen, Hashimoto, Simone, Bansal, Aruna T., Hedlin, Gunila, Hu, Xuguang, Murray, Clare, Nordlund, Bjorn, Shaw, Dominick, Singer, Florian, Sterk, Peter, Sousa, Ana R., Van Aalderen, Wim, Wagers, Scott, Yu, Wen, Roberts, Graham and Bates, Stewart (2017) Late Breaking Abstract - Comparison of the blood transcriptomic profiles of adults and children from the U-BIOPRED asthma study. European Respiratory Journal, 50 (Suppl 61), [OA3442]. (doi:10.1183/1393003.congress-2017.OA3442).
Abstract
Background: We have previously reported altered gene expression in adults with asthma compared to healthy controls from the U-BIOPRED study (Bigler, 2016). Altered transcripts may define dysregulated biological pathways and identify novel therapeutic targets. We hypothesised that similar dysregulation would be seen in children with asthma. Aim: To compare blood transcriptomic profiles of children and adults with asthma. Methods: Affymetrix blood transcriptomic profiles of severe asthmatic adult non-smokers, n=152, were compared to mild moderate asthmatics, n=50 (Shaw, 2015; Fleming, 2015). Profiles of school-aged children with severe asthma, n=75, were compared to mild moderate asthmatics, n=37, and in the preschool age group severe wheeze, n=62, was compared to mild moderate wheeze, n=42. Differentially expressed genes (DEG) were identified as probe sets with maximum median group intensity >log2 5, with a significant (raw P≤0.01) change ≥ 20%. Overlapping genes were determined and pathway analysis performed. Results: We found 1887 DEG comparing severe and mild moderate asthmatic adults. Only 28 DEG were found between the severe wheeze and mild pre-school age children, with a larger signature (569 DEG) in the school aged children. 480 genes were specific to school-aged children and 1801 specific to adults, with 89 DEG in common between the adults and school-aged children. Conclusions: Preschool age children were poorly defined in terms of blood transcriptomics by the clinical definitions used. While the school-aged children showed some DEG overlap with the adults, they were distinct in many DEG and pathways indicating that childhood and adult asthma may be mechanistically different.
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