Introduction: Bronchiectasis (BE) and chronic obstructive pulmonary disease (COPD) share similar clinical characteristics and are frequently co-diagnosed (BE-COPD). BE-COPD is associated with worse outcomes but the mechanisms of this are unknown.

Aim: To investigate differences in the lung microbiome in BE and BE-COPD overlap.

Methods: Stable BE and BE-COPD patients were enrolled from a single UK centre. BE-COPD was defined using the objective ROSE criteria. The sputum microbiome was evaluated using 16S rRNA sequencing. Alpha-diversity was analysed using Shannon Wiener (SWDI), Chao1 (CI) and Simpson Index (SI). Results were validated in the EMBARC-BRIDGE cohort from UK, Italy and Spain.

Results: 281 patients were enrolled (BE n=176, BE-COPD n=105), 52.3% female, age 68 (±12.6). Proteobacteria were the most abundant phyla, and Haemophilus and Streptococcus the most abundant genera. Alpha diversity was significantly lower in BE-COPD group (SWDI p=0.02, CI p=0.04, SI p=0.03). No difference in beta-diversity was seen between the groups (PERMANOVA, p=0.33). Random Forest analysis identified reduced commensal taxa in the BE-COPD group, including lower Neisseria, Prevotella, Campylobacter and Fusobacterium. 208 patients were enrolled in the EMBARC BRIDGE cohort (BE=147, BE-COPD=61). Alpha diversity was reduced in the BE-COPD group (SWDI p=0.06, CI p=0.02, SI p=0.03) and there were significant changes in beta-diversity (PERMANOVA, p=0.02). Similarly, Random Forest detected depletion of Neisseria, Prevotella, Campylobacter in the BE-COPD arm.

Conclusion: We demonstrate in two large cohorts that BE-COPD is associated with reduced microbial diversity and depletion of anti-inflammatory commensal taxa.