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Cell-free DNA levels associate with COPD exacerbations and mortality
Sarah A Ware1, Corrine R Kliment2, Luca Giordano1
1Department of Medicine, Division of Cardiology, Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, 200 Lothrop Street BST W1044, Pittsburgh, PA, 15261, USA.
Respiratory Research
|January 18, 2024
Summary
Plasma cell-free mitochondrial and nuclear DNA (cf-mtDNA and cf-nDNA) can predict chronic obstructive pulmonary disease (COPD) progression. Elevated cf-nDNA is linked to increased mortality risk in COPD patients.
Area of Science:
- Biomarkers
- Genomics
- Pulmonary Medicine
Background:
- Chronic obstructive pulmonary disease (COPD) lacks reliable indicators for predicting disease progression and phenotypes.
- Cigarette smoke damages nuclear and mitochondrial DNA, releasing cell-free DNA (cf-DNA) into circulation.
- Plasma cf-DNA may reflect disease physiology and clinical outcomes in COPD.
Purpose of the Study:
- To investigate the association between plasma cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) levels and COPD severity, exacerbations, and mortality.
- To evaluate the potential of cf-mtDNA and cf-nDNA as predictive biomarkers in COPD.
Main Methods:
- Quantification of mtDNA and nDNA copy numbers in plasma from 2,702 participants in the ECLIPSE study.
- Analysis of associations between cf-mtDNA and cf-nDNA levels and clinical parameters, including disease severity, exacerbations, and mortality.
Main Results:
- Plasma cf-mtDNA levels correlated positively with future exacerbation rates in mild/moderate and severe COPD patients, and those with high eosinophil counts.
- Plasma cf-nDNA levels were positively associated with an increased mortality risk (HR 1.33).
- Combined low cf-mtDNA and high cf-nDNA further elevated mortality risk (HR 1.62).
Conclusions:
- Plasma cf-mtDNA and cf-nDNA show potential as quantitative biomarkers for assessing COPD severity and progression.
- Integrating cf-mtDNA and cf-nDNA into clinical assessments may improve patient management and outcome prediction in COPD.
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