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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.

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|January 18, 2024
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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.

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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.