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Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations

Authors Avriel A, Rozenberg D, Raviv Y, Heimer D, Bar-Shai A, Gavish R, Sheynin J, Douvdevani A

Received 20 May 2016

Accepted for publication 26 September 2016

Published 9 December 2016 Volume 2016:11(1) Pages 3153—3161

DOI https://doi.org/10.2147/COPD.S113256

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 4

Editor who approved publication: Dr Richard Russell


Avital Avriel,1 Dmitry Rozenberg,2 Yael Raviv,1 Dov Heimer,1 Amir Bar-Shai,3 Rachel Gavish,4 Jony Sheynin,5,6 Amos Douvdevani6

1Department of Medicine, Pulmonology Institute, Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel; 2Division of Respirology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 3Department of Medicine, Pulmonology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, 4Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel; 5Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; 6Department of Clinical Biochemistry, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel

Background: Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality. Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD. The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival.
Methods: This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE. Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls. Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival.
Results: A total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included. The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016–2,319) compared to 781 ng/mL (IQR 523–855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209–636) for healthy controls (P<0.0001, for both comparisons). cfDNA was correlated with partial arterial pressure of carbon dioxide (PaCO2, r=0.35) and pH (r=-0.35), P=0.01 for both comparisons. In a multivariable analysis, PaCO2 was the only independent predictor of cfDNA. Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO2), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV1% (hazard ratio 1.92, 95% confidence interval 0.93–3.95, P=0.08).
Conclusion: Plasma cfDNA might offer a novel technique to identify COPD patients at increased risk of poor outcomes, but the prognostic utility of this measurement requires further study.

Keywords: chronic obstructive pulmonary disease, exacerbation, cell-free DNA, biomarker, prognosis


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