Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations

Abstract

<b>Rationale:</b> Lung dysbiosis promotes airway inflammation and decreased local immunity, potentially playing a role in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). <b>Objectives:</b> We sought to determine the relationship between sputum microbiome at the time of AECOPD hospitalization and 1-year mortality in a COPD cohort. <b>Methods:</b> We used sputum samples from 102 patients hospitalized because of AECOPD. All subjects were followed for 1 year after discharge. The microbiome profile was assessed through sequencing of 16S rRNA gene. Microbiome analyses were performed according to 1-year mortality status. To investigate the effect of α-diversity measures and taxon features on time to death, we applied Cox proportional hazards regression models and obtained hazard ratios (HRs) associated with these variables. <b>Measurements and Main Results:</b> We observed significantly lower values of α-diversity (richness, Shannon index, evenness, and Faith's Phylogenetic Diversity) among nonsurvivors (<i>n</i> = 19, 18.6%) than survivors (<i>n</i> = 83, 81.4%). β-Diversity analysis also demonstrated significant differences between both groups (adjusted permutational multivariate ANOVA, <i>P</i> = 0.010). The survivors had a higher relative abundance of <i>Veillonella</i>; in contrast, nonsurvivors had a higher abundance of <i>Staphylococcus</i>. The adjusted HRs for 1-year mortality increased significantly with decreasing α-diversity. We also observed lower survival among patients in whom sputum samples were negative for <i>Veillonella</i> (HR, 13.5; 95% confidence interval, 4.2-43.9; <i>P</i> < 0.001) or positive for <i>Staphylococcus</i> (HR, 7.3; 95% confidence interval, 1.6-33.2; <i>P</i> = 0.01). <b>Conclusions:</b> The microbiome profile of sputum in AECOPD is associated with 1-year mortality and may be used to identify subjects with a poor prognosis at the time of hospitalization.