Upper airway ciliary dysfunction in bronchiectasis: The EMBARC cilia cohort study

Mucociliary clearance is a key component of the pathophysiology of bronchiectasis but cilia function is poorly defined. This study aims to characterize nasal ciliary function in bronchiectasis and examine associations with disease severity, infection, inflammation and outcome. Adults with bronchiectasis and healthy volunteers were recruited to the international observational study EMBARC-BRIDGE. Individuals with a known diagnosis of Primary Ciliary Dyskinesia (PCD) were excluded. Nasal respiratory epithelium was sampled by brush biopsy. Ciliary function was assessed by high-speed video microscopy in primary samples and following re-differentiation in air-liquid interface (ALI) culture. Ciliary parameters (cilia length, angle, amplitude, clearance, frequency and ciliation) were quantified and compared with disease severity, microbiology, inflammation and future risk of exacerbations. 171 participants with bronchiectasis were recruited (54% female, age 68years (59-74)). Bronchiectasis nasal brushings showed greater epithelial disruption compared to healthy volunteers (p=0.0006). Six individuals with previously undiagnosed PCD were identified and excluded. In the remaining bronchiectasis cohort, ciliary beat frequency and length were similar to healthy controls. In contrast ciliary beat amplitude, angle, amplitude per second and clearance capacity, were significantly reduced (all p<0.001). These parameters were restored following ALI culture. Regenerated epithelia from bronchiectasis donors exhibited reduced ciliated area. Ciliary dysfunction was strongly associated with future risk of severe exacerbations. The upper airway epithelium is disrupted in bronchiectasis; ciliary movement is impaired and is associated with future risk of exacerbation. Ciliary dysmotility is reversible following ALI culture. This indicates that impaired ciliary function is secondary to the airway environment and therapeutically targetable.