Differences in pathophysiology may underlie asthma heterogeneity, and bronchial microbiota composition has been associated with the degree of airway hyperresponsiveness among patients with mild to moderate asthma. In this study, we investigated relationships between the bronchial airway microbiome and disease features in severe asthma.

Methods: Bacterial microbiota represented in protected bronchial brushings from 30 severe asthma subjects were profiled using a 16S rRNA-based phylogenetic microarray (PhyloChip; Second Genome Inc., San Bruno, CA). Clinical, physiologic, and airway inflammation measures were analyzed for relationships to airway bacterial community structure and composition.

Results: Airway bacterial community structure was associated with between-visit differences in Asthma Control Questionnaire (ACQ) scores (P < 0.01), sputum neutrophilia (P < 0.08), and body mass index (BMI) (P < 0.03). The specific microbiota associated with change in ACQ score and with sputum neutrophilia differed markedly from those associated with BMI. Proteobacteria composed more than 70% of bacterial taxa correlated with sputum neutrophilia (Benjamini-Hochberg-adjusted P < 0.05), including such bacterial families as Bacillaceae, Helicobacteraceae, and Moraxellaceae. Proteobacteria constituted 93% of taxa positively correlated with ACQ score difference, whereas Actinobacteria composed 80% of taxa negatively correlated with this variable. In contrast, Bacteroidetes accounted for 54% of the taxa strongly associated with BMI, including a greater relative abundance of Prevotellaceae and Porphyromonadaceae among subjects with BMI greater than or equal to 30.

Conclusions: Distinct airway bacterial community composition was associated with specific clinical and inflammatory features of severe asthma in this group of patients. We speculate that particular microbiota members may be involved in the induction or modulation of specific inflammatory processes that contribute to severe asthma and corresponding clinical phenotype.