Systemic Inflammation in Bronchiectasis: Data from the EMBARC-BRIDGE Study

Background 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. Methods 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. Results 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. Conclusion 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.