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

Abstract

<b>Rationale:</b> Infection is a key disease driver in bronchiectasis, and the upper-airway microbiome has been known to shape the lower-airway microbiome. <b>Objective:</b> To evaluate the relationship between the upper-airway microbiome, mucociliary function, and clinical outcomes in bronchiectasis. <b>Methods:</b> 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 <i>Pseudomonas</i>, <i>Haemophilus,</i> and <i>Staphylococcus</i>. <b>Measurements and Main Results:</b> 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 (<i>P</i> = 0.002), and β-diversity analysis revealed distinct microbiome profiles associated with disease severity and severe exacerbation (permutational multivariate ANOVA, <i>P</i> = 0.021 and <i>P</i> = 0.001, respectively). Random forest analysis identified <i>Pseudomonas</i> as being associated with severe bronchiectasis (Bronchiectasis Severity Index ⩾9) and severe exacerbations. The genus-level relative taxon abundance of <i>Pseudomonas</i> was well correlated with <i>Pseudomonas aeruginosa</i> 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 (<i>P</i> = 0.95). <b>Conclusions:</b> The upper-airway microbiome is associated with disease severity and severe exacerbation of bronchiectasis.