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COPD Origins: Understanding Extracellular Matrix (ECM) Remodelling using bio-imaging techniques

C W Kong, T Havelock, M Bennett, J M B Sand, S R Rønnow, C M Spalluto, S Karl, K Ostridge, H Burke, A Freeman, A Fazleen, T Wilkinson
European Respiratory Journal 2022 60: 352; DOI: 10.1183/13993003.congress-2022.352
C W Kong
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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T Havelock
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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M Bennett
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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J M B Sand
2Nordic Bioscience, Biomarkers and Research, Herlev, Denmark, HERLEV, Denmark
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S R Rønnow
2Nordic Bioscience, Biomarkers and Research, Herlev, Denmark, HERLEV, Denmark
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C M Spalluto
3Clinical and Experimental Sciences, Faculty of Medicine, University Hospital Southampton, Southampton, UK, Southampton, United Kingdom
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S Karl
3Clinical and Experimental Sciences, Faculty of Medicine, University Hospital Southampton, Southampton, UK, Southampton, United Kingdom
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K Ostridge
4Translational Science and Experimental Medicine, Research and Early development, Respiratory and Immunology R&D BioPharmaceuticals, Astrazeneca, Gothenburg, Sweden, Gothenburg, Sweden
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H Burke
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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A Freeman
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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A Fazleen
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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T Wilkinson
1Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK, Southampton (Hampshire), United Kingdom
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Abstract

Introduction: Probe-based confocal laser endomicroscopy (pCLE) images the elastin structure in the airway walls whilst serum markers of protein fragments (neo-epitopes) of elastin and collagen are associated with disease activity in COPD. This study aims to characterise ECM remodelling in COPD by pCLE imaging and the serological assessment of neo-epitopes.

Methods: We completed pCLE-bronchoscopy in 15 patients with COPD and 18 healthy subjects. Alveolar dimensions were measured and the alignment of airway fibres was quantified using our novel image analysis software. We assessed serum levels of neo-epitopes in 61 patients with COPD and 54 healthy controls for the evaluation of elastin (ELP-3, EL-NE, EL-CG) and collagen type I (C1M), type IV (C4M) and type VI (C6M) remodelling.

Results: COPD was associated with larger alveolar diameter (352µm +/− 15 vs 293µm +/− 27, p<0.001) and greater disorder of airway elastin fibre alignment related to markers of small airways disease including FEV1/FVC, MEF25%-75% and mean lung density expiratory/inspiratory ratio. COPD was associated with higher serum levels of ELP-3, EL-CG, C1M, C6M whilst ELP-3, EL-CG, C1M, C4M and C6M were related to lung function impairment (see Fig1).

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Conclusion: Novel imaging and neo-epitope biomarkers identify evidence of ECM remodelling which underpin the development of abnormal lung function and insights into key mechanisms driving the origins of COPD.

  • COPD - diagnosis
  • Biomarkers
  • Measurement properties

Footnotes

Cite this article as Eur Respir J 2022; 60: Suppl. 66, 352.

This article was presented at the 2022 ERS International Congress, in session “-”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2022
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COPD Origins: Understanding Extracellular Matrix (ECM) Remodelling using bio-imaging techniques
C W Kong, T Havelock, M Bennett, J M B Sand, S R Rønnow, C M Spalluto, S Karl, K Ostridge, H Burke, A Freeman, A Fazleen, T Wilkinson
European Respiratory Journal Sep 2022, 60 (suppl 66) 352; DOI: 10.1183/13993003.congress-2022.352

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COPD Origins: Understanding Extracellular Matrix (ECM) Remodelling using bio-imaging techniques
C W Kong, T Havelock, M Bennett, J M B Sand, S R Rønnow, C M Spalluto, S Karl, K Ostridge, H Burke, A Freeman, A Fazleen, T Wilkinson
European Respiratory Journal Sep 2022, 60 (suppl 66) 352; DOI: 10.1183/13993003.congress-2022.352
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