Sputum Azurocidin-1 is a marker of disease severity and microbiome dysbiosis in adult bronchiectasis, and increases in response to Rhinovirus challenge in COPD.

<bold>Introduction:</bold> Azurocidin-1 (AZU1) is a neutrophil granule protein similar in structure to neutrophil elastase but without protease activity. Its’ role in bronchiectasis and in acute viral infection is unknown. <bold>Methods:</bold> We measured AZU1 by ELISA in soluble sputum from 142 bronchiectasis patients enrolled in the European, multicentre EMBARC-BRIDGE study. We linked results to clinical severity markers and microbial composition at species level measured by full length 16s rRNA sequencing. We then measured AZU1 in broncho-alveolar lavage samples from days 5, 9, and 42 following rhinovirus challenge in 9 COPD patients, 9 healthy smokers and 8 healthy non-smokers. <bold>Results:</bold> In the bronchiectasis cohort, AZU1 was higher in patients with bacterial infection, previous hospitalisation and greater radiological severity. The proteobacteria Haemophilus influenzae and Pseudomonas aeruginosa were the most differentially abundant species defining patients with high AZU1 while Rothia mucilaginosa differentiated those with low AZU1. Alpha diversity was lower in patients with high sputum AZU1. In the Rhinovirus challenge study, median sputum AZU1 level rose from 6.23 μg/ml (IQR 2.39-8.77) at baseline to 73.44 μg/ml (IQR 29.58-196.6) by day 9 post-challenge in patients with COPD (p <0.001). There was no significant change in sputum AZU1 among either healthy controls or current smokers. Participants with high AZU1 by day 9 had higher upper respiratory tract symptoms score, higher sputum viral load and higher sputum mucin concentration. <bold>Conclusions:</bold> AZU1 is a novel inflammatory biomarker in chronic lung diseases.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa5322
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
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article
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article

Sputum Azurocidin-1 is a marker of disease severity and microbiome dysbiosis in adult bronchiectasis, and increases in response to Rhinovirus challenge in COPD.

Francesco Blasi, Arietta Spinou, Josje Altenburg, Michal Shteinberg et al.
Chronic Obstructive Pulmonary Disease (COPD) Research
article

Sputum Azurocidin-1 is a marker of disease severity and microbiome dysbiosis in adult bronchiectasis, and increases in response to Rhinovirus challenge in COPD.

Francesco Blasi, Arietta Spinou, Josje Altenburg, Michal Shteinberg, Emma J. Johnson, Amy Gilmour, Patrick Mallia, Oriol Sibila, Michael R. Loebinger, Charles Haworth, Felix C. Ringshausen, Raja Dhar, Katerina Dimakou, Sebastian Lennox Johnston, Pieter Goeminne, Erin Cant, Natalie Lorent, Aran Singanayagam, Sanjay H. Chotirmall, Tobias Welte, Amelia Shoemark, James Chalmers, Anthony De Soyza, Morven Shuttleworth, Stefano Aliberti, Joseph Footit, Megan Crichton, Merete Bridget Long
article en

Abstract

<bold>Introduction:</bold> Azurocidin-1 (AZU1) is a neutrophil granule protein similar in structure to neutrophil elastase but without protease activity. Its’ role in bronchiectasis and in acute viral infection is unknown. <bold>Methods:</bold> We measured AZU1 by ELISA in soluble sputum from 142 bronchiectasis patients enrolled in the European, multicentre EMBARC-BRIDGE study. We linked results to clinical severity markers and microbial composition at species level measured by full length 16s rRNA sequencing. We then measured AZU1 in broncho-alveolar lavage samples from days 5, 9, and 42 following rhinovirus challenge in 9 COPD patients, 9 healthy smokers and 8 healthy non-smokers. <bold>Results:</bold> In the bronchiectasis cohort, AZU1 was higher in patients with bacterial infection, previous hospitalisation and greater radiological severity. The proteobacteria Haemophilus influenzae and Pseudomonas aeruginosa were the most differentially abundant species defining patients with high AZU1 while Rothia mucilaginosa differentiated those with low AZU1. Alpha diversity was lower in patients with high sputum AZU1. In the Rhinovirus challenge study, median sputum AZU1 level rose from 6.23 μg/ml (IQR 2.39-8.77) at baseline to 73.44 μg/ml (IQR 29.58-196.6) by day 9 post-challenge in patients with COPD (p <0.001). There was no significant change in sputum AZU1 among either healthy controls or current smokers. Participants with high AZU1 by day 9 had higher upper respiratory tract symptoms score, higher sputum viral load and higher sputum mucin concentration. <bold>Conclusions:</bold> AZU1 is a novel inflammatory biomarker in chronic lung diseases.

Humanitas University (IT), Nanyang Technological University (SG), University of Dundee (GB), King's College London (GB), University of Milan (IT), Royal Papworth Hospital (GB), Medizinische Hochschule Hannover (DE), Royal Brompton Hospital (GB), Carmel Medical Center (IL), Vlaamse Vereniging voor Obstetrie en Gynaecolo (BE), Fortis Hospital (IN), Mylan (Switzerland) (CH), The London College (GB), Sotiria General Hospital (GR), Universitat de Barcelona (ES), Newcastle University (GB), KU Leuven (BE)
Medical Research Council
Openalex Percentile: Top 62%
Chronic Obstructive Pulmonary Disease (COPD) Research
DOISourceOpenAlex
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