Molecular characterisation of COPD exacerbations

<b>Background:</b> COPD exacerbations are heterogeneous events; identifying endotypes may improve treatment. <b>Methods:</b> Multicentre UK study where patients were enrolled during stability and exacerbation. Sputum obtained at both time points underwent 16S rRNA sequencing, real-time PCR for bacterial quantification and viral detection. Blood eosinophil counts were measured. Inflammatory markers were measured in sputum supernatant by multiplex assay. <b>Results:</b> 55 exacerbations and matched stable events were profiled. Bacteria were found in 58.2% of exacerbations and one or more viruses were found in 32.7%. The most common organism overall was H. influenzae (23.6%) and the most common virus was rhinovirus (18.2%). Overall, no difference was observed in microbiome beta-diversity between stability and exacerbation, PERMANOVA,p=0.8. Alpha diversity was reduced at exacerbation (mean difference 0.11, p=0.04). There were marked differences between bacterial, eosinophilic and viral exacerbations in beta-diversity (PERMANOVA,p=0.003) with significantly elevated IL-1β, TNF-α, VEGF, elastase, resistin, CXCL8 and LL-37 in bacterial exacerbations with elevated IL-5 in eosinophilic events, and IFN-γ in viral events. These markers showed an incremental increase with bacterial load with increases in TNF-α, CXCL8 and VEGF and IL-10 above 10(6)cfu/ml and increased NE and IL-1β above 10(7)cfu/ml (figure 1). <b>Conclusion:</b> COPD exacerbations can be classified into inflammatory endotypes.