Rationale: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality in Australia. People with COPD suffer increasingly frequent exacerbations, contributing to disease progression. However, the basis of these exacerbations is not well understood.
Methods: We conducted an in-depth investigation of the COPD lung, using metagenomics and metatranscriptomics, to analyse sputum and bronchial washes from 70 Queenslanders. This cohort included individuals experiencing stable disease, infectious exacerbations, non-infectious exacerbations, or lung cancer.
Results: Contrary to expectations, our analysis revealed minimal differences in the microbiome between stable disease and infectious exacerbations; instead, we observed considerable microbiome heterogeneity across participants and disease states. Pseudomonas aeruginosa (Pa) and Haemophilus influenzae (Hi) were commonly identified using both methods; Streptococcus pneumoniae was also common, but unlike Pa and Hi, was rarely dominant. Moraxella catarrhalis was identified in just two cases, and influenzavirus, coronavirus NL63, RSV were identified once each. Less common COPD pathogens such as Acinetobacter baumanii, Achromobacter xylosoxidans, Escherichia coli, and Staphylococcus aureus were seen rarely. A number of microbes not commonly reported in COPD were observed, including Tropheryma whipplei (Whipple’s disease) and Actinomyces israelii (actinomycosis). Notably, Candida spp. were frequently detected in COPD sputa and demonstrated higher activity compared with healthy sputa, suggesting an underappreciated role in COPD pathogenesis. Antimicrobial resistance determinants were uncommon, suggesting that most microbes found in the COPD lung originate from environmental sources or the oral cavity rather than nosocomial.
Conclusions: Pa, Hi, and S. pneumoniae were common in Queenslanders with both stable and exacerbating COPD, whereas M. catarrhalis was uncommon, highlighting potential geographic differences in pathogen prevalence. Considerable diversity was uncovered, emphasising the need for comprehensive diagnostics in COPD management. Such diagnostics could revolutionise our understanding of COPD, enabling the development of targeted therapies and interventions to reduce morbidity and mortality. Low antimicrobial resistance, suggests targeted therapies are underutilised in this cohort; a hypothesis that would benefit from a clinical trial. Our study sheds light on the intricate environment of the COPD lung, and underscores the importance of advanced microbial profiling techniques in COPD diagnosis and management.