Real-time mass spectrometric identification of metabolites characteristic of chronic obstructive pulmonary disease in exhaled breath

Real-time mass spectrometric identification of metabolites characteristic of chronic obstructive pulmonary disease in exhaled breath
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DOI:
10.1016/j.clinms.2018.02.003
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发表时间:
2018-01-01
影响因子:
2.1
通讯作者:
Zenobi, Renato
Zenobi, Renato
中科院分区:
医学4区
文献类型:
--
作者:
Bregy, Lukas;Nussbaumer-Ochsner, Yvonne;Zenobi, Renato

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背景:分析呼出气的新质谱 (MS) 技术有可能更好地定义气道疾病。在这里,我们介绍了我们的工作,利用实时 MS 分析慢性阻塞性肺疾病 (COPD) 患者呼出气中的挥发性有机化合物 (VOC),并将这种疾病特异性呼吸分析与功能性疾病标志物联系起来。方法:在一项匹配队列研究中,根据 GOLD 标准招募了 COPD 患者。使用二次电喷雾电离 - 高分辨率 MS (SESI-HRMS) 进行非靶向 MS 呼出气分析。 结果:22 名 COPD 患者(平均年龄 58.6 +/- 6.9 岁,FEV1 预测值 58.5 +/- 19.9%,吸烟年数 32.4 +/- 19.2 包年)和 14 名对照者(平均年龄 58.1 +/- 8.1 岁)的呼出气年,FEV1 102.5 +/- 11.3% 预测,23.6 +/- 12.5 包年吸烟)使用 SESI-HRMS 进行分析。从 1441 个不同的特征中,鉴定出 43 个标记物,可以区分两组,准确度为 89% (CI 74-97%),敏感性为 93%,特异性为 86%。这些标记物被确定为氧化应激过程的代谢物,例如肺肌肉退化产生的脂肪酸、醛和氨基酸。结论:SESI-MS 的实时呼吸分析可以对呼出气体进行分子分析,可以将 COPD 患者与匹配的健康对照区分开来,并提供对疾病发病机制的见解。
Background: New mass spectrometry (MS) techniques analysing exhaled breath have the potential to better define airway diseases. Here, we present our work to profile the volatile organic compounds (VOCs) in exhaled breath from patients with chronic obstructive pulmonary disease (COPD), using real-time MS, and relate this disease-specific breath profile to functional disease markers.Methods: In a matched cohort study, patients with COPD, according to GOLD criteria, were recruited. Exhaled breath analysis by untargeted MS was performed using secondary electrospray ionization - high-resolution MS (SESI-HRMS).Results: Exhaled breath from 22 patients with COPD (mean age 58.6 +/- 6.9 years, FEV1 58.5 +/- 19.9% predicted, 32.4 +/- 19.2 pack years smoking) and 14 controls (mean age 58.1 +/- 8.1 years, FEV1 102.5 +/- 11.3% predicted, 23.6 +/- 12.5 pack years smoking) was analysed using SESI-HRMS. From 1441 different features, 43 markers were identified that allowed discrimination between the two groups with an accuracy of 89% (CI 74-97%), a sensitivity of 93%, and a specificity of 86%. The markers were determined to be metabolites of oxidative stress processes, such as fatty acids, aldehydes and amino acids, resulting from lung muscle degradation.Conclusion: Real-time breath analysis by SESI-MS allows molecular profiling of exhaled breath, can distinguish patients with COPD from matched healthy controls and provides insights into the disease pathogenesis.