Dysbiosis of the nasal microbiome is associated with prospective acute exacerbation of COPD.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is often associated with respiratory viral infection and the need for increased medical intervention. The nasal mucosa plays a critical role in infection susceptibility and severity, with the nasal microbiome shaping mucosal immunity. This study investigated the association between the bacterial nasal microbiome and AECOPD. Participants included 41 individuals with COPD and 15 healthy non-COPD controls. Nasal microbiome composition was assessed from nasal epithelial lining fluid and compared at baseline between healthy participants and individuals with COPD, stratified by AECOPD history. COPD subjects who experienced one or more AECOPD in the year prior to enrollment were categorized as Ever AECOPD. COPD participants without a history of AECOPD in the prior year were categorized as Never AECOPD. Prospective exacerbation data were collected and used in a case-control analysis to identify clinical and microbiological markers predictive of future AECOPD in COPD-diagnosed subjects.

RESULTS: We found two distinct nasal microbiome architectures with enrichment of protective taxa (healthy signature) or pathobionts (pathogenic signature). Nasal microbiome analysis demonstrated significant differences in nasal bacterial composition between COPD-diagnosed individuals with prior AECOPD (Ever AECOPD) compared to healthy controls. For COPD individuals with no prior AECOPD (Never AECOPD), we identified two underlying community structures; Cluster 1 subjects harbored a nasal microbiome significantly similar to healthy controls (healthy signature) and Cluster 2 subjects were significantly similar to the Ever AECOPD cohort (pathogenic signature). We evaluated the baseline microbiome of COPD-diagnosed participants based on the occurrence of at least one AECOPD 1-year after baseline sample collection (prospective AECOPD) and found that the nasal microbiome was associated with the occurrence of future AECOPD events. Prospective exacerbation was associated with reduced relative abundance of Dolosigranulum pigrum. Further analysis by qPCR showed that decreased D. pigrum abundance was associated with lower lung function and higher risk of future AECOPD.

CONCLUSIONS: Our data indicates that the nasal microbiome is associated with AECOPD phenotypes. Moreover, participants with decreased nasal Dolosigranulum pigrum abundance had lower lung function and a higher risk of future exacerbations. These findings suggest that D. pigrum may serve as a biomarker for AECOPD risk; however, validation of these findings in a larger multicenter cohort is needed. Video Abstract.