Ruzsics Istvan, Nagy Lajos, Keki Sandor, Sarosi Veronika, Illes Balazs, Illes Zsolt, Horvath Ildiko, Bogar Lajos, Molnar Tihamer
a 1 Department of Pulmonology, University of Pecs , Pecs , Hungary.
b 2 Department of Applied Chemistry, University of Debrecen , Debrecen , Hungary.
COPD. 2016;13(2):139-45. doi: 10.3109/15412555.2015.1045973. Epub 2015 Oct 29.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains a major cause of mortality. Clinical criteria of AECOPD are subjective. Biomarkers for AECOPD may aid in the initiation of early treatment. Increased production of asymmetric and symmetric dimethylarginine (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD.
L-arginine metabolites quantified by high-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects.
Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p < 0.001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p < 0.001, respectively). A cut-off value ≥0.57 for SDMA was an independent variable to confirm AECOPD in a regression model (OR: 1.632, p = 0.001). All markers were significantly higher in the sera of both patient groups compared to the controls (p < 0.05, respectively).
COPD is associated with elevated L-arginine, ADMA and SDMA serum levels. In patients with AECOPD, production of ADMA and SDMA are more pronounced presumably due to more severe hypoxic insult. Methylated arginine derivatives in the sera may help early recognition of AECOPD.
慢性阻塞性肺疾病急性加重（AECOPD）仍是主要的死亡原因。AECOPD的临床标准具有主观性。AECOPD的生物标志物可能有助于早期治疗的启动。不对称和对称二甲基精氨酸（ADMA、SDMA）产量增加与缺氧有关。在慢性阻塞性肺疾病（COPD）中，ADMA升高导致L-精氨酸分解发生变化，从而导致气道阻塞。我们旨在比较有和没有AECOPD患者的血清ADMA、SDMA和L-精氨酸水平。
对32例COPD患者、12例AECOPD患者和30名健康受试者进行前瞻性研究，通过高效液相色谱法对静脉血样本中的L-精氨酸代谢物进行定量，并检测部分毛细血管氧分压。
与稳定期COPD相比，AECOPD患者的ADMA和SDMA均显著升高（分别为p = 0.004和p < 0.001）。毛细血管中的氧含量与血清ADMA浓度相关。然而，AECOPD和稳定期COPD之间L-精氨酸的浓度没有差异。ADMA和SDMA对AECOPD的诊断具有较高的敏感性和特异性（AUC分别为：0.81，p = 0.001；0.91，p < 0.001）。在回归模型中，SDMA≥0.57的截断值是确诊AECOPD的独立变量（OR：1.632，p = 0.001）。与对照组相比，两组患者血清中的所有标志物均显著升高（分别为p < 0.05）。
COPD与血清L-精氨酸、ADMA和SDMA水平升高有关。在AECOPD患者中，ADMA和SDMA的产生更为明显，可能是由于更严重的缺氧损伤。血清中的甲基化精氨酸衍生物可能有助于AECOPD的早期识别。
