Year: 2026
Type: article
Study design: Observational 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.
Authors: Chloe Hughes, Merete B Long, Jamie Stobo, Emma D Johnson, Kateryna Viligorska, Holly Lind, Eve McIntosh, Isavella Petrou, Qingyou Du, Chandani Hennayake, Morven Shuttleworth, Jaa Ming New, Pieter C Goeminne, Michal Shteinberg, Anthony De Soyza, Stefano Aliberti, Josje Altenburg, Charles S Haworth, Oriol Sibila, Eva Polverino, Michael Loebinger, Amelia Shoemark, Felix C Ringshausen, Natalie Lorent, Katerina Dimakou, Adelina Amorim, Raul Mendez, Anne Marie McLaughlin, Zoe Borrill, Robert Lord, Simon Finch, Francesco Blasi, Faisel Khan, James D Chalmers
Institutions: University of Dundee, Ninewells Hospital, Carmel Medical Center, Freeman Hospital, National Institute for Health and Care Research, Newcastle University, Humanitas University, IRCCS Humanitas Research Hospital, Amsterdam University Medical Centers, University of Cambridge, Royal Papworth Hospital, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Harefield Hospital, Imperial College London, Medizinische Hochschule Hannover, Universitair Ziekenhuis Leuven, KU Leuven, Sotiria General Hospital, Universidade do Porto, Hospital de São João, Hospital Universitari i Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, St. James's Hospital, North Manchester General Hospital, Manchester University NHS Foundation Trust, Wythenshawe Hospital, NHS Fife, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Oxford
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7225454456