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

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/thorax-2025-223305

Authors


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Funder identifier:
10.13039/100004330
Grant:
no grant number
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Funder identifier:
http://dx.doi.org/10.13039/100031315
Grant:
no award/grand number - independent research grant
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Funder identifier:
https://ror.org/01xsqw823


Publisher:
BMJ Publishing Group
Journal:
Thorax More from this journal
Pages:
thorax-2025-223305
Article number:
thorax-2025-223305
Publication date:
2026-02-13
Acceptance date:
2026-01-11
DOI:
EISSN:
1468-3296
ISSN:
0040-6376


Language:
English
Keywords:
Pubs id:
2379409
Local pid:
pubs:2379409
Source identifiers:
3792974
Deposit date:
2026-02-24
ARK identifier:
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