Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations.
Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations.
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DOI：
10.2147/copd.s113256
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发表时间：
2016
影响因子：
2.8
通讯作者：
Douvdevani A
中科院分区：
文献类型：
--
作者：
Avriel A;Rozenberg D;Raviv Y;Heimer D;Bar-Shai A;Gavish R;Sheynin J;Douvdevani A
慢性阻塞性肺疾病急性加重（COPDE）与发病率和死亡率增加相关。游离 DNA (cfDNA) 是一种与多种疾病状态的临床结果相关的新型生物标志物，但尚未在 COPD 中进行研究。本研究的目的是评估 COPDE 期间的 cfDNA 水平，评估 cfDNA 与临床参数的关联，并探讨 cfDNA 水平对长期生存的预后影响。这是一项观察性研究，评估了因 COPDE 入院的患者的 cfDNA 水平。将 COPDE 患者的血浆 cfDNA 水平与匹配的稳定 COPD 患者和健康对照进行比较。使用多变量和 Cox 回归分析来评估 cfDNA 水平与血气参数和长期生存的关联。总共纳入 62 名患者（46 名男性，1 秒用力呼气量 [FEV1] 38%±13%）。 COPDE 患者入院时的中位 cfDNA 水平为 1,634 ng/mL（四分位距 [IQR] 1,016–2,319），而与年龄和疾病严重程度相匹配的稳定 COPD 患者为 781 ng/mL (IQR 523–855)，健康对照为 352 ng/mL (IQR 209–636)（P<0.0001，对于比较）。 cfDNA 与二氧化碳分动脉压 (PaCO2, r=0.35) 和 pH (r=-0.35) 相关，两个比较的 P=0.01。在多变量分析中，PaCO2 是 cfDNA 的唯一独立预测因子。使用 1,924 ng/mL 的 cfDNA 水平（PaCO2 异常阈值），那些水平较高的人在根据年龄、性别和 FEV1% 进行调整后，有 5 年死亡风险增加的趋势（风险比 1.92，95% 置信区间 0.93–3.95，P=0.08）。血浆 cfDNA 可能提供一种新技术来识别 COPD 患者不良结果风险增加的情况，但这种测量的预后效用需要进一步研究。
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. 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. 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). 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.