S91 Gateway to the hidden zone: using pCLE to study relationships between elastin remodelling and small airways disease in the COPD lung

Introduction Small airways disease (SAD) is a hallmark of COPD and often precedes the development of airflow obstruction and clinically evident emphysema. SAD requires study however, this has been complicated by the absence of direct sampling and imaging techniques and is beyond the resolution of CT. Probe-based confocal laser endomicroscopy (pCLE) produces fluorescence images of tissue obtained in vivo during endoscopy. pCLE can image extra-cellular matrix (ECM) remodelling in the submucosa of airway walls. We developed imaging and analysis techniques and used these to describe the ECM remodelling and relationships to features of SAD and early COPD. Methods We performed pCLE-bronchoscopy to directly visualise the airways in 8 never smokers (mean [+/- SD] age, 48 +/- 8), 8 smokers with normal spirometry (mean [+/- SD] age, 55 +/- 5) and 12 patients with COPD (mean [+/- SD] age, 61 +/- 4, mean [+/- SD] FEV1%, 83.5% +/- 13.5). Alveolar opening dimensions were measured, and the structural disorder caused by the remodelling process was objectively quantified and expressed as an elastin linearity score (ELS) using novel quantitative image analysis software. Results COPD was associated with larger mean alveolar opening diameter (350.1µm ± 15.1 vs 289.8µm ± 21.6, p = 0.000) and greater cross-sectional area. There was greater disorder of airway elastin fibre alignment, even in mild COPD (mean [± SD] ELS, 54.9 ± 6 vs 44.7 ± 9, p = 0.002). ELS was inversely correlated with several lung function and CT imaging parameters including FEV1% (r = -0.477, p = 0.016) FEV1/FVC% (r = -0.640, p = 0.001) MEF25–75% (r = -0.649, p = 0.001), and mean expiratory to inspiratory ratio of the mean lung density (E/I MLD) (r = 0.438, p =0.032). Conclusions This is the first pCLE study to describe airway microscopic changes related to lung function and CT indices of small airways disease in COPD. These results suggest this novel imaging analysis technique may help uncover the earliest signs of airway remodelling in COPD offering new insights into key mechanisms of disease and potential novel endpoints for development of novel disease modifying treatments for this important disease.