Measurements of desmosine and isodesmosine by mass spectrometry in COPD
Measurements of desmosine and isodesmosine by mass spectrometry in COPD
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DOI：
10.1378/chest.06-2251
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发表时间：
2007-05-01
期刊：
影响因子：
9.6
通讯作者：
Turino, Gerard M.
中科院分区：
文献类型：
--
作者：
Ma, Shuren;Lin, Yong Y.;Turino, Gerard M.
目的：应用质谱仪(MS)直接测定尿液、血浆和痰中桥连素(D)和异桥素(I)作为弹性蛋白降解的标记物，作为α(1)抗胰蛋白酶缺乏症(AATD)和非AATD相关COPD患者弹性蛋白降解的标志物。背景：COPD患者的肺发生弹性蛋白损伤，可以通过测定体液中的D和I作为弹性蛋白降解的特异性标志物，利用MS的特异性和敏感性进行监测。方法：血浆酸解、24小时尿液和痰标本测定，然后用色谱分离进行质谱分析。结果：各病例组的血浆D、I水平均显著高于对照组。AATD患者的血浆α(1)-抗胰蛋白酶(AAT)水平高于COPD患者。24小时尿液中D和I的总水平在对照组和患者之间无显著差异，但显示尿液中D和I的游离浓度，在COPD伴和不伴AAT的患者中有统计学意义的升高。AATD患者痰中的D和I水平高于AAT正常的COPD患者。结论：MS可以敏感和特异地分析体液中的D和I。痰中D和I的定量，以及血浆中D和I的增加，以及尿中D和I的游离成分的升高，提供了COPD患者的特征指标，并可与病程和/或治疗相关。
Objectives: Application of mass spectrometry (MS) for direct measurements of desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of elastin degradation in patients with alpha(1)-antitrypsin deficiency (AATD) and non-AATD-related COPD.Background: In COPD patients, the lungs undergo elastin injury, which can be monitored by measurements of D and I in body fluids as specific markers of elastin degradation using the specificity and sensitivity of MS.Methods: Acid hydrolysis of blood plasma, 24-h urine and sputum measurements, followed by chromatographic separation for mass spectrometric analysis. Results: Each patient group had levels of plasma D and I that were statistically significantly higher than those of control subjects. AATD patients had higher levels than COPD patients with normal alpha(1)-antitrypsin (AAT) levels. Twenty-four-hour urine measurements demonstrated no significant difference in total levels of D and I among control subjects and patients but showed a free (unbound) concentration of D and I in urine, which was statistically significantly higher in patients with COPD with and without AAT. The D and I levels in the sputum of patients with AATD exceeded the levels in COPD patients with normal AAT levels.Conclusions: MS allows a sensitive and specific analysis of D and I in body fluids. The quantification of D and I in sputum, along with increases of D and I in plasma and an elevated free component of D and I in urine provide indexes that characterize patients with COPD and can be followed in relation to the course of the disease and/or therapy.