Sputum microbiome α-diversity is a key feature of the COPD frequent exacerbator phenotype

ABSTRACT Background The lung microbiome is an inflammatory stimulus whose role in chronic obstructive pulmonary disease (COPD) pathogenesis is incompletely understood. We hypothesized that the frequent exacerbator phenotype is associated with decreased α-diversity and increased lung inflammation. Our objective was to assess correlations between the frequent exacerbator phenotype, the microbiome, and inflammation longitudinally during exacerbation-free periods. Methods We conducted a case-control longitudinal observational study of the frequent exacerbator phenotype and characteristics of the airway microbiome. Eighty-one subjects (41 frequent and 40 infrequent exacerbators) provided nasal, oral, and sputum microbiome samples at two visits over 2-4 months. Exacerbation phenotype, relevant clinical factors, and sputum cytokine values were associated with microbiome findings. Results The frequent exacerbator phenotype was associated with lower sputum microbiome α-diversity (p=0.0031). This decrease in α-diversity among frequent exacerbators was enhanced when the sputum bacterial culture was positive (p<0.001). Older age was associated with decreased sputum microbiome α-diversity (p=0.0030). Between-visit β-diversity was increased among frequent exacerbators and those who experienced a COPD exacerbation between visits (p=0.025, p=0.014). Sputum cytokine values did not differ based on exacerbation phenotype or other clinical characteristics. IL-17A was negatively associated with α-diversity, while IL-6 and IL-8 were positively associated with α-diversity (p=0.012, p=0.012, p=0.0496). IL-22, IL-17A, and IL-5 levels were positively associated with Moraxella abundance (p=0.027, p=0.0014, p=0.0020). Conclusions Even during exacerbation-free intervals, the COPD frequent exacerbator phenotype is associated with decreased sputum microbiome α-diversity and increased β-diversity. Decreased sputum microbiome α-diversity and Moraxella abundance are associated with lung inflammation.