Upper-Airway Microbiome, Mucociliary Function, and Clinical Outcomes in Bronchiectasis: Data from the EMBARC-BRIDGE Study.

Rationale: Infection is a key disease driver in bronchiectasis, and the upper-airway microbiome has been known to shape the lower-airway microbiome. Objective: To evaluate the relationship between the upper-airway microbiome, mucociliary function, and clinical outcomes in bronchiectasis. Methods: Nasopharyngeal swabs were collected from 344 patients with bronchiectasis enrolled across five European centers. A total of 104 patients had nasopharyngeal samples obtained at the 1-year follow-up. Microbiome composition was assessed according to Bronchiectasis Severity Index and severe exacerbations. The α- and β-diversity were measured using the Chao1 and Bray-Curtis indices, respectively. Random forest analysis was performed. Dysbiosis was defined as >10% relative abundance of pathogenic taxa comprising Pseudomonas, Haemophilus, and Staphylococcus. Measurements and Main Results: Of the 344 patients, 200 (58.1%) were female (median age, 68 yr; IQR, 59-75 yr). α-Diversity significantly differed according to disease severity (P = 0.002), and β-diversity analysis revealed distinct microbiome profiles associated with disease severity and severe exacerbation (permutational multivariate ANOVA, P = 0.021 and P = 0.001, respectively). Random forest analysis identified Pseudomonas as being associated with severe bronchiectasis (Bronchiectasis Severity Index ⩾9) and severe exacerbations. The genus-level relative taxon abundance of Pseudomonas was well correlated with Pseudomonas aeruginosa growth in the sputum culture. Patients with nasopharyngeal dysbiosis had more severe respiratory symptoms, showed epithelial disruption on nasal epithelial biopsy, and experienced more severe exacerbation over a 1-year follow-up period than those in the nondysbiosis group. The microbiome profiles were relatively stable between baseline and 1-year follow-up (P = 0.95). Conclusions: The upper-airway microbiome is associated with disease severity and severe exacerbation of bronchiectasis.