Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by small airway inflammation and alveolar damage. Recent evidence has demonstrated that low-grade systemic inflammation is an important hallmark of COPD which correlates with higher mortality rates. However, the cellular and transcriptomic alterations of blood immune cells in COPD patients have not yet been deciphered. Specifically, despite their contribution to lung pathophysiology, the neutrophil population structure remains undetermined.
Aims and objectives: We assessed the heterogeneity of blood immune cells in COPD patients and focused on the prediction value of neutrophil signatures in both blood and bronchoalveolar fluid (BALF).
Methods: Peripheral blood and BALF from control and COPD patients was analyzed with multi-color flow cytometry and scRNA-seq. The identified neutrophil signatures in both compartments were correlated with patient clinical data.
Results: We observed increased oxidative phosphorylation and cell migration but reduced translation initiation in blood leukocytes from COPD patients. Neutrophil frequencies were associated with lung function decline and they comprised distinct transcriptomic states. Notably, a blood subset expressing interferon response genes strongly correlated with lung function decline, smoking habits and exacerbation frequency in COPD patients. Similarly, neutrophil gene signatures in BALF discriminated among mild and more severe COPD stages.
Conclusions: Blood leukocytes undergo transcriptomic reprogramming in COPD. Moreover, neutrophils from peripheral blood and BALF are highly heterogeneous and express gene signatures that predict disease severity.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA1596.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
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 2021