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

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 t...

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Autores principales: Avriel, Avital, Rozenberg, Dmitry, Raviv, Yael, Heimer, Dov, Bar-Shai, Amir, Gavish, Rachel, Sheynin, Jony, Douvdevani, Amos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158140/
https://www.ncbi.nlm.nih.gov/pubmed/28003743
http://dx.doi.org/10.2147/COPD.S113256
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author Avriel, Avital
Rozenberg, Dmitry
Raviv, Yael
Heimer, Dov
Bar-Shai, Amir
Gavish, Rachel
Sheynin, Jony
Douvdevani, Amos
author_facet Avriel, Avital
Rozenberg, Dmitry
Raviv, Yael
Heimer, Dov
Bar-Shai, Amir
Gavish, Rachel
Sheynin, Jony
Douvdevani, Amos
author_sort Avriel, Avital
collection PubMed
description 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 [FEV(1)] 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 (PaCO(2), r=0.35) and pH (r=−0.35), P=0.01 for both comparisons. In a multivariable analysis, PaCO(2) was the only independent predictor of cfDNA. Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO(2)), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV(1)% (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.
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spelling pubmed-51581402016-12-21 Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations Avriel, Avital Rozenberg, Dmitry Raviv, Yael Heimer, Dov Bar-Shai, Amir Gavish, Rachel Sheynin, Jony Douvdevani, Amos Int J Chron Obstruct Pulmon Dis Original Research 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 [FEV(1)] 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 (PaCO(2), r=0.35) and pH (r=−0.35), P=0.01 for both comparisons. In a multivariable analysis, PaCO(2) was the only independent predictor of cfDNA. Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO(2)), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV(1)% (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. Dove Medical Press 2016-12-09 /pmc/articles/PMC5158140/ /pubmed/28003743 http://dx.doi.org/10.2147/COPD.S113256 Text en © 2016 Avriel et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Avriel, Avital
Rozenberg, Dmitry
Raviv, Yael
Heimer, Dov
Bar-Shai, Amir
Gavish, Rachel
Sheynin, Jony
Douvdevani, Amos
Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations
title Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations
title_full Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations
title_fullStr Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations
title_full_unstemmed Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations
title_short Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations
title_sort prognostic utility of admission cell-free dna levels in patients with chronic obstructive pulmonary disease exacerbations
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158140/
https://www.ncbi.nlm.nih.gov/pubmed/28003743
http://dx.doi.org/10.2147/COPD.S113256
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