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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. [ABSTRACT FROM AUTHOR]

Background: Despite the high prevalence of co‐existing bronchiectasis and asthma (asthma‐bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. Objective: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. Methods: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady‐state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase‐chain‐reaction). Patients were followed‐up to record exacerbation and spirometry. Results: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria–virus co‐detection increased less substantially at acute exacerbations (AE) onset than at steady‐state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow‐up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate‐to‐severe bronchiectasis and non‐atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). Conclusion: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS. [ABSTRACT FROM AUTHOR]

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus–predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis. [ABSTRACT FROM AUTHOR]