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

Abstract 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.

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Journal
American Journal of Respiratory and Critical Care Medicine
Published
2026-11-06
DOI
https://doi.org/10.1093/ajrccm/aamag590
Primary Topic
Cystic Fibrosis Research Advances
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article
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article

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

Francesco Blasi, Robert W. Lord, Chandani Kumari HENNAYAKE, Josje Altenburg et al.
American Journal of Respiratory and Critical Care Medicine
Cystic Fibrosis Research Advances
article

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

Francesco Blasi, Robert W. Lord, Chandani Kumari HENNAYAKE, Josje Altenburg, Michal Shteinberg, Kateryna Viligorska, Faisel Khan, Raúl Méndez, Oriol Sibila, Michael R. Loebinger, CHARLES S. HAWORTH, Simon Finch, Anne Marie McLaughlin, Felix C. Ringshausen, Eva Polverino, Holly Lind, Katerina Dimakou, Jamie Stobo, Pieter Goeminne, Eve Mcintosh, Natalie Lorent, Zöe Borrill, Chloe Hughes, Amelia Shoemark, Anthony De Soyza, Adelina A. Amorim, Morven K. Shuttleworth, Qingyou Du, Merete Bridget Long, Emma D Johnson, James D. Chalmers, Isavella Petrou, Jaa Ming New, Stefano Aliberti
article en

Abstract

Abstract 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.

American Journal of Respiratory and Critical Care Medicine
Humanitas University (IT), University of Dundee (GB), Universidade do Porto (PT), University of Milan (IT), University of Cambridge (GB), Royal Papworth Hospital (GB), Universitair Ziekenhuis Leuven (BE), North Manchester General Hospital (GB), Freeman Hospital (GB), Ninewells Hospital (GB), Harefield Hospital (GB), NHS Fife (GB), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Hospital de São João (PT), Hospital Universitari i Politècnic La Fe (ES), Medizinische Hochschule Hannover (DE), National Institute for Health and Care Research (GB), University of Oxford (GB), Manchester University NHS Foundation Trust (GB), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES), Vall d'Hebron Institut de Recerca (ES), Carmel Medical Center (IL), Hospital Clínic de Barcelona (ES), Vall d'Hebron Hospital Universitari (ES), Wythenshawe Hospital (GB), Amsterdam University Medical Centers (NL), St. James's Hospital (IE), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), IRCCS Humanitas Research Hospital (IT), Instituto de Investigación Sanitaria La Fe (ES), Sotiria General Hospital (GR), Imperial College London (GB), Universitat de Barcelona (ES), Newcastle University (GB), KU Leuven (BE)
Openalex Percentile: Top 13%
Cystic Fibrosis Research Advances
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