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

Abstract

<b>Introduction:</b> 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. <b>Methods:</b> 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. <b>Results:</b> COPD was associated with larger alveolar diameter (352µm +/− 15 vs 293µm +/− 27, p&lt;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). <b>Conclusion:</b> 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.