Introduction: Exacerbations are heterogeneous events with a major impact on morbidity and mortality in COPD. The aim of this study was to use transcriptomics to characterise the immune response during exacerbation and recovery.

Methods: Stabilised whole blood was collected from patients hospitalised with exacerbation of COPD (n=32) and matched controls without infection (n=38). mRNAseq was performed on blood samples obtained at day 1 of admission to hospital. Key comparisons were COPD vs control, severe exacerbation (defined by requirement for oxygen or non-invasive ventilation) vs mild exacerbations, and recovery by day 29 (defined as no longer requiring oxygen or ventilatory support).

Results: Patients with COPD (mean age 63 years (±12.7), 59.4% female), vs controls (mean age 67 years (±15.6), 57.9% female). There were 1472 significant differentially expressed genes at onset of exacerbation (adjusted p<0.05). The most altered pathways included completement activation, cell adhesion, extracellular matrix organisation and regulation of immune response. There were 196 differentially expressed genes between severe (n=15) and non-severe exacerbation (n=17, adjusted p<0.05), with significant pathways including negative regulation of apoptosis, oxygen transport and cellular iron homeostasis. In patients (n=12) who had not recovered by day 29, there were 454 differentially expressed genes (adjusted p<0.05) at baseline.

Conclusion: Profound changes to the peripheral blood transcriptome are observed in exacerbations of COPD with relationships to severity and delayed recovery.