Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

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.

Sputum pathogen spectrum and clinical outcomes of upper respiratory tract infection in bronchiectasis exacerbation: a prospective cohort study.

Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis (AE). Between March 2017 and December 2021, we prospectively collected sputum from adults with bronchiectasis. We stratified AEs into events related (URTI-AE) and unrelated to URTI (non-URTI-AE). We captured URTI without onset of AE (URTI-non-AE). We did bacterial culture and viral detection with polymerase chain reaction, and explored the pathogen spectrum and clinical impacts of URTI-AE via longitudinal follow-up. Finally, we collected 479 non-AE samples (113 collected at URTI-non-AE and 225 collected at clinically stable) and 170 AE samples (89 collected at URTI-AE and 81 collect at non-URTI-AE). The viral detection rate was significantly higher in URTI-AE (46.1%) than in non-URTI-AE (4.9%) and URTI-non-AE (11.5%) (both P < 0.01). Rhinovirus [odds ratio (OR): 5.00, 95% confidence interval (95%CI): 1.06-23.56, P = 0.03] detection was independently associated with URTI-AE compared with non-URTI-AE. URTI-AE tended to yield higher viral load and detection rate of rhinovirus, metapneumovirus and bacterial shifting compared with URTI-non-AE. URTI-AE was associated with higher initial viral loads (esp. rhinovirus, metapneumovirus), greater symptom burden (higher scores of three validated questionnaires) and prolonged recovery compared to those without. Having experienced URTI-AE predicted a greater risk of future URTI-AE (OR: 10.90, 95%CI: 3.60-33.05). In summary, URTI is associated with a distinct pathogen spectrum and aggravates bronchiectasis exacerbation, providing the scientific rationale for the prevention of URTI to hinder bronchiectasis progression.

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 COPD. RESEARCH QUESTION: What are the characteristics of MCD of the nasal epithelium and its association with disease severity and inflammatory endotypes in adults with bronchiectasis? STUDY DESIGN AND METHODS: In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy control participants who underwent brushing of the 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% showed secondary MCD, and 16.2% showed primary plus secondary MCD. Compared with healthy control participants, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1, and RSPH9 (but not Ezrin) that were more prominent in moderate to severe bronchiectasis. MCD pattern scores largely were consistent between upper and lower airways and between large-to-medium and small airways in bronchiectasis. Coexisting nasal diseases and asthma did not confound nasal ciliary ultrastructural marker expression significantly. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly an ultrastructural abnormality, was notable in patients with mild bronchiectasis who showed blood or sputum eosinophilia. INTERPRETATION: Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis.

Decreased Systemic and Airway Sirtuin 1 Expression in Adults With Bronchiectasis.

Aim: Whether accelerated aging, reflected by sirtuin 1 (SIRT1) expression, is implicated in bronchiectasis remains largely unknown. We sought to determine the patterns of SIRT1 and other aging markers in systemic circulation and airways and their expression levels associated with bronchiectasis severity and exacerbation. Methods: We enrolled 132 patients with bronchiectasis and 50 healthy subjects in a prospective cohort study to profile aging markers in systemic circulation and recruited 36 patients with bronchiectasis and 32 disease controls (idiopathic pulmonary fibrosis or tumors) in a cross-sectional study to profile aging markers in bronchial epithelium of both large-to-medium and small airways. We profiled aging marker expression from peripheral blood mononuclear cells and enumerated the positively stained cells for detection of aging marker expression in bronchial epithelium. Results: Compared with healthy controls, the relative telomere length (median: 0.88 vs. 0.99, p = 0.009), SIRT1 (median: 0.89 vs. 0.99, p = 0.002), and Ku80 (median: 0.87 vs. 0.96, p < 0.001) expression levels were consistently lower in the peripheral blood mononuclear cells among patients with bronchiectasis and modestly discriminated patients with bronchiectasis from healthy controls. No remarkable changes in SIRT1, telomere length, or Ku70 were identified at onset of exacerbation. Within the bronchial epithelium, the percentage of positively stained cells was lower for SIRT1 (median: 25.1 vs. 57.2%, p < 0.05) and numerically lower for p16 (median: 40.0 vs. 45.1%) and p21 (median: 28.9 vs. 35.9%) in patients with bronchiectasis than in disease controls (p > 0.05). Conclusion: SIRT1 was downregulated in systemic circulation and bronchiectatic airways, which was independent of disease severity and lung function impairment.