3 Key Takeaways
Plain English Summary- 01Core Finding
Observational international multi-centre study of adults with bronchiectasis (EMBARC-BRIDGE).
- 02Study Evidence
Tested in a observational cohort study (487 patients) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
What This Means for You
Bronchiectasis is associated with a systemic neutrophil and endothelial (blood-vessel lining) inflammatory signature linked to disease severity and risk of severe exacerbations, alongside altered but functionally-responsive circulating neutrophils.
The Discovery
Neutrophilic inflammation in the airways is associated with exacerbation risk in patients with bronchiectasis. Systemic inflammation and neutrophil function are less characterised. The aim of this study was to investigate the relationship between systemic inflammation and neutrophil function with severity of disease and clinical outcomes. Observational international multi-centre study of adults with bronchiectasis (EMBARC-BRIDGE). Serum inflammatory profiling was performed in 487 patients using Olink® proteomics, and associations with key clinical and patient reported outcomes, including severe exacerbations during follow-up, were analysed. In a sub-study, peripheral blood neutrophils from bronchiectasis patients and controls were analysed for surface activation and functional markers, and functional responses including degranulation and neutrophil extracellular trap formation. Systemic inflammatory profiling revealed a dominant neutrophil-endothelial (blood-vessel lining) signature. Several proteins including PR3, AZU1, MPO, the soluble IL-33 receptor ST2, and the cellular stress marker GDF-15 were associated with increased disease severity using the bronchiectasis severity index, lower lung function, increased symptoms and for many markers, higher rates of severe exacerbations during follow-up. Neutrophils from bronchiectasis patients exhibited reduced surface CD11b and increased CXCR2, with lower CD11b correlating with lower lung function. Basal degranulation was reduced in bronchiectasis, whereas responsiveness to LPS stimulation was preserved.
How It Works, Simply
This pulmonology research focuses on inflammation · Receptor targeting. Researchers evaluated it using an observational cohort study (487 patients) at the real-world cohort stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Observational international multi-centre study of adults with bronchiectasis (EMBARC-BRIDGE).
- 02Study Evidence
Tested in a observational cohort study (487 patients) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
Biological Mechanism & Study Design
Study Design & Cohort
Observational cohort study
Observational cohort study (487 patients) · Real-World Cohort
Biological Pathway & Modality
Inflammation · Receptor targeting
Intervention: Systemic Inflammation in Bronchiectasis: Data from the EMBARC-BRIDGE Study
Experimental Findings & Endpoints
Neutrophilic inflammation in the airways is associated with exacerbation risk in patients with bronchiectasis.
Systemic inflammation and neutrophil function are less characterised. The aim of this study was to investigate the relationship between systemic inflammation and neutrophil function with severity of disease and clinical outcomes.
Observational international multi-centre study of adults with bronchiectasis (EMBARC-BRIDGE). Serum inflammatory profiling was performed in 487 patients using Olink® proteomics, and associations with key clinical and patient reported outcomes, including severe exacerbations during follow-up, were analysed.
In a sub-study, peripheral blood neutrophils from bronchiectasis patients and controls were analysed for surface activation and functional markers, and functional responses including degranulation and neutrophil extracellular trap formation. Systemic inflammatory profiling revealed a dominant neutrophil-endothelial signature.
Several proteins including PR3, AZU1, MPO, the soluble IL-33 receptor ST2, and the cellular stress marker GDF-15 were associated with increased disease severity using the bronchiectasis severity index, lower lung function, increased symptoms and for many markers, higher rates of severe exacerbations during follow-up. Neutrophils from bronchiectasis patients exhibited reduced surface CD11b and increased CXCR2, with lower CD11b correlating with lower lung function.
Basal degranulation was reduced in bronchiectasis, whereas responsiveness to LPS stimulation was preserved.
Clinical Translation & Practice Context
Bronchiectasis is associated with a systemic neutrophil and endothelial inflammatory signature linked to disease severity and risk of severe exacerbations, alongside altered but functionally-responsive circulating neutrophils.
The Bottom Line · Clinical Pearl
“Bronchiectasis is associated with a systemic neutrophil and endothelial inflammatory signature linked to disease severity and risk of severe exacerbations, alongside altered but functionally-responsive circulating neutrophils.”
Published in American Journal of Respiratory and Critical Care Medicine · Current Stage: Real-World Cohort