Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by chronic respiratory symptoms due to abnormalities of the airways and/or alveoli that cause airflow obstruction. It is a leading cause of death worldwide. While alterations in airway bacterial community have been linked to exacerbation frequency, the underlying mechanisms remain unclear. We aimed to characterize associations between airway bacterial community structure and exacerbation history in stable COPD patients and to identify candidate microbial markers that could assist in risk assessment for the clinical management of COPD patients. Sixty-two stable COPD patients were enrolled and categorized into two groups based on their exacerbation history: low risk (LR) and high risk (HR) of exacerbation. Sputum samples were collected and analyzed using both bacterial extended culture and 16S rRNA gene sequencing. The combination of these approaches provided complementary insights, enabling a more comprehensive characterization of the bacterial community. To our knowledge, this is the first study to combine these two approaches in this context and to evaluate their relative performance in detecting microbiological markers associated with exacerbation risk. Microbial composition analysis revealed a loss of α-diversity in HR patients based on extended culture data, a finding not corroborated by sequencing. This discrepancy suggests that the observed impoverishment of diversity may primarily affect the viable fraction of the airway microbial community. The HR group also exhibited increased relative abundances of Pseudomonadota and Bacteroidota, alongside a marked decrease in relative abundances of Lactobacillus and Streptococcus. Notably, significant reductions in the proportion of positive samples were observed at the species level for Streptococcus salivarius and Streptococcus mutans. A comparison of the two methods underlined that 16S rRNA gene sequencing identified five additional phyla and 84 genera not detected by culture, notably strict anaerobes. However, extended culture demonstrated robust sensitivity in detecting Enterobacterales and the pathogenic Moraxella and Pseudomonas. This study revealed microbiological features linked to exacerbation history in stable COPD patients, highlighting the need for future functional and longitudinal research to validate these airway bacterial community signatures and develop targeted preventive strategies.