Bacterial and viral microbiomes in COPD exacerbations of unidentified cause

BACKGROUND: In a quarter of COPD exacerbations etiology remains unknown after standard microbiology, but culture-independent techniques allow for the identification of undetected causes. AIM: To analyse bacterial and viral microbiomes in bronchial secretions from severe COPD patients during exacerbations considered as non-infectious according to bacterial cultures and PCR for respiratory viruses. METHOD: Sputum samples negative for bacteria and virus obtained at 5 exacerbations in 4 severe COPD patients were compared with stability samples, analyzing bacterial and viral microbiomes by metagenomics. An exacerbation-related increase >20% in bacterial or viral relative abundance over stability values, and/or a predominance >50%, were considered as significant for etiologic diagnosis. RESULTS: In exacerbations most of the 16sRNA bacterial sequences were assigned to phyla Firmicutes (47%) and Proteobacteria (38%), and viral reads to eukaryotic viruses (94%), with 4 families accounting for 95% of the observations ( Retroviridae, Herpesviridae, Papillomaviridae and Anelloviridae ). Bacterial 16sRNA was significantly increased from stability in all exacerbations, for the genera Xanthamonadaceae-g (1), Pseudomonas (1), Moraxella (1), Corynebacterium (1) and Streptococcus (1). Viral increase of the same magnitude was found in 1 exacerbation by Cytomegalovirus . Change in bacterial abundance was paralleled by increases in related bacteriophages and prophages ( Pseudomonas and Streptococcus ) in 2 cases. CONCLUSIONS: COPD exacerbations of unknown cause after standard microbiology techniques are mainly attributable to bacterial infections, and paralleled by the presence of bacteriophage/prophage counterparts.