Comparison of mRNA expression showed widespread changes in the circulating CD8+ but not CD4+ T-cells from patients with severe asthma. No changes were observed in the CD4+ and CD8+ T-cells in non-severe asthmatics versus healthy controls. Bioinformatics analysis showed that the changes in CD8+ T-cell mRNA expression were associated with multiple pathways involved in T-cell activation. As with mRNAs, we also observed widespread changes in expression of non-coding RNA species including natural antisense, pseudogenes, intronic long ncRNAs and long intergenic long ncRNAs in CD8+ T-cells from severe asthmatics. Measurement of the miRNA expression profile showed selective down-regulation of miR-28-5p in CD8+ T-cells and reduction of miR-146a and miR-146b in both CD4+ and CD8+ T-cells.