Bacterial colonization at stable disease influences exacerbation severity in COPD

<b>Rationale:</b> COPD exacerbations are heterogenous, where eosinophilic patients with dysbiosis appeared to have more severe exacerbation. Periostin (PERI) has been shown to be involved in eosinophils (EOS) recruitment and tissue repair. We hypothesized that dysbiosis and eosinophilic inflammation at stable disease will influence exacerbation severity, where serum PERI and blood EOS could be used to identify a subgroup of patients with dysbiosis and increased exacerbation severity. <b>Methods:</b> BEAT:COPD was an observational 12-month study. Serum PERI from 203 COPD patients were measured on an Elecsys assay and sputum 16S V3-V5 rRNA was pyrosequenced. Biomarker subgroups were defined by PERI and EOS. The association of biomarker subgroup with clinical metrics was assessed using multivariate regression. Measures of microbial diversity and the relative abundance of taxa were compared among biomarker subgroups. <b>Results:</b> At stable visits, PERIlow (&lt;50ng/ml) patients had lower alpha-diversity and higher abundance of Haemophilus compared to PERIhigh (=50ng/ml) (p&lt;.05). At exacerbation, beta-diversity between PERIlow versus PERIhigh was different with higher abundance of Proteobacteria in PERIlow subgroup (p&lt;.05). These differences were not observed between the EOS subgroups (&lt;300, =300 cells/µL). Interestingly, EOShighPERIlow patients had increased abundance of Haemophilus and Moraxella compared to EOShighPERIhigh at stable and exacerbations, where EOShighPERIlow patients had more severe exacerbations with greater FEV1 decline (p&lt;.05). <b>Conclusions:</b> Our data suggests eosinophilic patients with low periostin had increased Proteobacteria colonization at stable and exacerbation, which influenced exacerbation severity.