Quantitative Assessment of Pulmonary Extracellular Matrix Remodelling as a Platform to Enable Regenerative Lung Interventions

Aberrant remodelling of the lung extracellular matrix (ECM) is a key process in the development of chronic lung diseases but has not been the focus of work on lung regeneration to date. There is a need for new approaches to enable early detection and quantification of ECM derangement. Probe-based confocal laser endomicroscopy (pCLE) offers a promising solution, enabling direct imaging of the pulmonary ECM. This study aims to characterise ECM remodelling in COPD using pCLE imaging techniques. We conducted pCLE bronchoscopy on 12 volunteers with normal lung function, 19 former or current smokers exhibiting physiological signs of SAD, and 10 patients with mild to moderate COPD. We quantified the alignment of airway elastin fibres (ELS) using our in-house developed image analysis software. ELS was higher in subjects with COPD and the SAD group compared to healthy volunteers (94.01 (85.88-97.05), 83.23 (75.73-95.88), 72.43 (67.82-78.57), respectively, p=0.005), indicating greater disorder in elastin fibre alignment. ELS was also associated with physiological markers of SAD, including FEV1(%), FEV1/FVC, MEF25%-75%, AX, and R5-R20 (<xref>Table 1</xref>). <table-wrap><object-id>erjor;11/suppl_15/TP128/TP128T1</object-id><object-id>T1</object-id><object-id>TP128T1</object-id><label>Table 1.</label><caption> ELS correlations with spirometry and IOS parameters (*p<0.05) </caption><table><colgroup><col></col><col></col><col></col><col></col><col></col><col></col></colgroup><tbody><tr><td></td><td>FEV1</td><td>FEV1/FVC</td><td>MEF25%-75%</td><td>AX</td><td>R5-R20</td></tr><tr><td>ELS</td><td>-0.35*</td><td>-0.44*</td><td>-0.50*</td><td>0.360*</td><td>0.369*</td></tr></tbody></table></table-wrap> This study offers important insights into the role of elastin fibre organisation in COPD. Abnormalities in elastin fibre orientation can be detected even before spirometric changes become clinically significant. These findings highlight the potential of pCLE as a tool for assessment of ECM abnormalities enabling the assessment of new approaches to restore lung architecture and health.