B109-06 A Cellular Map of Pre-chronic Obstructive Pulmonary Disease

Abstract Rationale Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide. However, a considerable number of people present symptoms despite not qualifying for the GOLD criteria of a FEV1/FVC ratio 0.7. Current diagnostic criteria alone are thus not sufficient to screen for at-risk patients. The term Pre-COPD has therefore been introduced to define patients in whom spirometry is unable to detect airflow obstruction but who are at increased risk of subsequently developing COPD based on their symptoms and functional or structural abnormalities. Indeed, we have previously revealed that the lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodelling even in the absence of physiologic airway obstruction. Methods To understand the molecular profile of Pre-COPD patients, we have here generated the first single nuclei atlas of lung tissues isolated from Pre-COPD patients and compared with healthy controls and different stages of COPD. We performed single-nucleus sequencing using the10X platform from samples procured from 10 Pre-COPD patients, 20 mild COPD patients, 9 severe COPD patients, and 10 Control donors. Results We found a significant reduction of type I epithelial cells (AT1), endothelial cells, and terminal bronchiole associated secretory cells (TBASC) already in Pre-COPD. The marked reduction in TBASCs is consistent with the presence of small airway disease in Pre-COPD, as we revealed previously. Further, we found that severe COPD patients have a distinct transcriptomic profile compared to pre- and mild COPD, suggesting that severe COPD findings cannot be extrapolated to earlier stages. Conclusion Based on the transcriptomic profile, we have identified key cell types implicated in Pre-COPD pathology which opens avenues for further mechanistic insights into the development of COPD. This abstract is funded by: German Center for Lung Research (DZL)