Gene signalling heterogeneity in exacerbations of COPD determined by microarray analysis of PBMC mRNA

Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to aetiology, inflammatory pathways and inflammation severity. This study was designed to investigate one of the most fundamental paradigms: during inflammatory episodes, affected tissue sites "signal" to central lymphoid organs in order to initiate adaptive and innate responses. Evidence based on transcriptomic profiling indicates that this process involves functional programming of migratory immune cells before their release into circulation. Different inflammatory triggers induce the release of different combinations of molecular mediators, and recognition of these different mediators by myeloid and lymphoid precursors induces up-regulation of discrete groups of expressed genes. In exacerbations of COPD, identification of gene signalling in migrating immune cell populations has the potential to reveal new drug targets to control exacerbation progression. Through analysis of genome wide expression profiling of paired peripheral blood mononuclear cells (PBMC) samples collected during COPD exacerbations versus post convalescence this study has suggested the existence of three distinct COPD exacerbation subgroups as defined by exacerbation-associated gene expression phenotypes, namely T-cell predominant, innate cell predominant and a third pauci-immune subgroup.