Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis

BACKGROUND Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease. RESEARCH QUESTION What is the characteristic of MCD of the nasal epithelium and the association with disease severity and inflammatory endotypes in adults with bronchiectasis? STUDY DESIGNS AND METHODS In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy controls who underwent brushing of nasal epithelium. A subgroup of patients underwent bronchoscopy for bronchial epithelium sampling (n=13), elective surgery for bronchial epithelium biopsy (n=18), and blood sampling for next-generation sequencing (n=37). We characterized systemic and airway inflammatory endotypes in bronchiectasis. We conducted immunofluorescence assays to profile ultrastructural [dynein axonemal heavy chain 5 (DNAH5), dynein intermediate chain 1 (DNAI1), radial spoke head protein 9 (RSPH9)] and ciliogenesis marker expression (Ezrin). RESULTS MCD was present in 89.8% of patients with bronchiectasis, 67.6% had secondary MCD and 16.2% had primary plus secondary MCD. Compared with healthy controls, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1 and RSPH9 (but not ezrin), which were more prominent in moderate-to-severe bronchiectasis. MCD pattern scores were largely consistent between upper and lower airways, and between large-to-medium and small airways in bronchiectasis. Co-existing nasal diseases and asthma did not significantly confound nasal ciliary ultrastructural marker expression. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly ultrastructural abnormality, was notable in patients with mild bronchiectasis who had blood or sputum eosinophilia. INTERPRETATION Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis.