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. 2026 Feb 20:thorax-2025-223305.
doi: 10.1136/thorax-2025-223305. Online ahead of print.

Clinical, molecular and microbial characterisation of the eosinophilic endotype of bronchiectasis: data from the EMBARC-BRIDGE study

Jennifer Pollock  1 , Jeffrey T J Huang  1 , Morven Shuttleworth  1 , Merete B Long  1 , Hollian Richardson  1 , Daniela Alferes de Lima  1 , Elena Kuzmanova  1 , Clare Clarke  1 , Michal Shteinberg  2   3 , Stefano Aliberti  4   5 , Charles Haworth  6 , Sanjay Haresh Chotirmall  7   8 , Eva Polverino  9 , Pieter C Goeminne  10 , Michael Loebinger  11   12 , Natalie Lorent  13   14 , Felix C Ringshausen  15 , Oriol Sibila  16 , Eva Rodriguez-Suarez  17 , Christopher McCrae  18 , Amelia Shoemark  1 , James D Chalmers  19   20
Affiliations
Free article

Clinical, molecular and microbial characterisation of the eosinophilic endotype of bronchiectasis: data from the EMBARC-BRIDGE study

Jennifer Pollock et al. Thorax. .
Free article

Abstract

Objectives: Eosinophilic bronchiectasis is defined by a blood eosinophil count (BEC) ≥300 cells/µL, but blood eosinophils imperfectly reflect airway eosinophilic inflammation. Here, we investigated the relationship between eosinophilic airway inflammation, blood eosinophils and clinical severity in bronchiectasis and explored the phenotype associated with eosinophilic bronchiectasis.

Methods: Sputum from 180 patients with stable CT-confirmed bronchiectasis was utilised to investigate airway levels of eosinophil proteins (eosinophil peroxidase (EPX), eosinophil derived-neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein (MBP) and Galectin-10 (Gal-10)) using a novel stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. To profile eosinophilic bronchiectasis, a nested analysis of patients with BEC <150 cells/µL (n=52) and ≥300 cells/µL (n=49) was conducted.

Results: Sputum concentrations of Gal-10, ECP and EDN were weakly but significantly associated with radiological severity, FEV1 and sputum culture positivity for Pseudomonas aeruginosa. Airway eosinophil protein concentrations did not associate with exacerbation frequency. Total eosinophil protein concentration moderately correlated with BECs (r=0.33 95% CI 0.14 to 0.49, p=0.0007). Nested analysis revealed increased sputum PCR-positivity for P. aeruginosa (26.7% vs 7.7%, p=0.033) and an increased frequency of patients showing signs of Aspergillus sensitisation (defined as Aspergillus-specific IgE titres >0.35 kUA/L, 24.5% vs 3.8%) in eosinophilic bronchiectasis. Sputum inflammatory biomarkers and clinical parameters did not differ between groups.

Conclusions: LC-MS/MS can detect eosinophilic inflammation within bronchiectasis sputum. Weak associations between elevated airway eosinophil proteins, bronchiectasis severity and P. aeruginosa infection were observed. Direct measurement of eosinophilic airway inflammation provides additional information in addition to BECs. Eosinophilic bronchiectasis associated with P. aeruginosa infection and Aspergillus sensitisation.

Keywords: Bronchiectasis; Eosinophil Biology.

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Conflict of interest statement

Competing interests: MS: grants or contracts from GSK, Trudell Medical Int and Tel Aviv League for Lung Disease; Consulting fees from Astra Zeneca, Boehringer Ingelheim, Dexcel, Kamada, Synchrony Medical, Trumed, Vertex and Zambon; payment of honoraria from Astra Zeneca, Boehringer Ingelheim, GSK, Kamada, Sanofi and Insmed; support for attending meetings and/or travel from Boehringer Ingelheim Israel, Astra Zeneca Israel, Kamada, Rafa and GSK Israel; participation on a Data Safety Monitoring Board or Advisory Board from Bonus Biotherapeutics, Boehringer Ingelheim and Astra Zeneca; AJRCCM Associate Editor, management board member: Israeli Pulmonology Society, Israeli Society for Tuberculosis and Mycobacterial Diseases, Management Board member: EMBARC, editorial board member: ERJ, Chest and ERJ taskforce member: bronchiectasis guidelines; and receipt of equipment from Trudell Medical International for clinical trial. SA: grants or contracts from Insmed, Chiesi and Fisher and Paykel; royalties or licences from McGraw Hill; consulting fees from Insmed, Zambon, Astra Zeneca, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna Italy, Moderna TX, Boehringer Ingelheim, Chiesi farmaceutica Spa, MSD Italia S.r.l., Vertex Pharmaceuticals, BRAHMS GMBH, Physioassist SAS, AN2 Therapeutics, GlaxoSmithKline Spa; payment or honoraria from GlaxoSmithKline Spa, Thermofisher Scientific, INSMED Italy, INSMED Ireland Ltd, Boehringer Ingelheim, Zambon, Vertex Pharmaceuticals, Fondazione Internazionale Menarini; participation on a Data Safety Monitoring Board or Advisory Board - INSMED Incorporated, INSMED Italy, AstraZeneca UK Limited, MSD Italia S.r.l and Verona Pharma plc. CH: consulting fees from 30 Technology, AstraZeneca, BiomX, Chiesi, Infex, Insmed, LifeArc, Pneumagen, Vertex and Zambon; payment or honoraria from Chiesi, Insmed, Vertex and Zambon; payment for expert testimony from Zambon; and unpaid ECFS Board member. SC: grants or contracts from Singapore Ministry of Health’s National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-001356), Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (MOH-000710), Open Fund Individual Research Grant (MOH-000955), Singapore Ministry of Education under its AcRF Tier 1 Grant (RT1/22) (S.H.C), National Research Foundation Singapore under its Open Fund-Large Collaborative Grant (MOH-001636) administered by the Singapore Ministry of Health’s National Medical Research Council; consulting fees from CSL Behring, Boehringer Ingelheim, Pneumagen Ltd, Sanofi, Zaccha Pte Ltd.; payment or honoraria from Astra Zeneca and Chiesi Farmaceutici; participation on a Data Safety Monitoring Board or Advisory Board – Inovio Pharmaceuticals Inc. and Imam Abdulrahman Bin Faisal University. EP: grants or contracts from Grifols; consulting fees from Insmed, Grifols, Pfizer, Moderna, Chiesi, N2Therapeutics, Pari and Electromed; Payment or honoraria from Insmed, Pari, Teva, GSK, Pfizer, Moderna, Chiesi, Grifols and Vertex; support for attending meetings from Insmed; Director of the Scientific Relationship of ERS with European Union PG – Payment or honoraria from Insmed, RMEI, Astra Zeneca and GSK; support for attending meetings from Astra Zeneca; participation on a Data Safety Monitoring Board or Advisory Board – Boehringer, MSD and Pfizer; unpaid member of Belgian Respiratory Society Board Member. ML: consulting fees from Armata, 30T, Astra Zeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, Boehringer Ingelheim, Ethris, Mannkind, AN2 Therapeutics; payment or honoraria from Insmed. NL: ERJ taskforce member - bronchiectasis guidelines and Management board member: EMBARC. FR – grants or contracts from German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU/EFPIA) and iABC Consortium (including Alaxia, Basilea, Novartis and Polyphor), Mukoviszidose Institute, Novartis and Insmed Germany; consulting fees from Parion Service, Boehringer Ingelheim, Insmed and Chiesi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from I!DE Werbeagentur GmbH, Insmed, Grifols, Universitätsklinikum Frankfurt am Main, University Hospital Hamburg, AstraZeneca and Sanofi; participation on a Data Safety Monitoring Board or Advisory Board - Insmed, Boehringer Ingelheim, Parion Sciences and Chiesi; honorary roles in former coordinator of the ERN-LUNG Bronchiectasis Core Network, co-chair of the German Bronchiectasis Registry PROGNOSIS, member of the SteerCo of the European Bronchiectasis Registry EMBARC, PI of the German Center for Lung Research; other financial or non-financial interests AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Parion, Recode, Ruhr University-Bochum, University of Dundee and Vertex (fees for clinical trial participation paid to institution). CM: at the time of writing, CM was an employee of Astra Zeneca AS; grants and contracts from Astra Zeneca and LifeArc; consulting fees from Spirovant, Translate Bio and ReCode Therapeutics; payment of honoraria fees from Translate Bio, Ethris and Insmed; unpaid involvement in European Respiratory Society Clinical Research Collaborations (EMBARC, BEATPCD, AMR Lung). JC: grants or contracts from Astra Zeneca, Boehringer Ingelheim, Insmed, GSK, Grifols, Gilead Sciences, Trudell and Genentech; consulting fees from Astra Zeneca, Boehringer Ingelheim, Insmed, Genentech, Antabio, GSK, Grifols, Trudell, Pfizer and Zambon. All other authors report no Conflict of Interest.

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