Gulcev Makedonka, Reilly Cavan, Griffin Timothy J, Broeckling Corey D, Sandri Brian J, Witthuhn Bruce A, Hodgson Shane W, Woodruff Prescott G, Wendt Chris H
Department of Medicine.
Division of Biostatistics, School of Public Health.
Int J Chron Obstruct Pulmon Dis. 2016 Sep 29;11:2435-2446. doi: 10.2147/COPD.S107844. eCollection 2016.
Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD).
We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry. We used a mixed-effect model to compare metabolite levels in cases compared to controls and a paired -test to test for differences between days 0 and 30 in the AECOPD group.
We identified 377 analytes at a false discovery rate of 5% that differed between cases (day 0) and controls, and 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%). Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity.
Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity.
急性加重是慢性阻塞性肺疾病（COPD）发病的主要原因。本研究的目的是确定慢性阻塞性肺疾病急性加重（AECOPD）的代谢组学生物标志物。
我们通过质谱（MS）测定了33例AECOPD患者入院后24小时内（第0天）、30天后以及65例匹配对照的血浆中的代谢物。通过质谱选择性反应监测来测量单个代谢物。我们使用混合效应模型比较病例组与对照组的代谢物水平，并使用配对检验来检测AECOPD组第0天和第30天之间的差异。
我们在错误发现率为5%的情况下，确定了377种在病例组（第0天）和对照组之间存在差异的分析物，以及31种在AECOPD病例组第0天和第30天之间存在差异的分析物（错误发现率：5%）。与对照组相比，AECOPD第0天时色氨酸水平降低，这与吲哚胺2,3-双加氧酶活性增加相对应。
AECOPD患者具有独特的代谢组学特征，包括色氨酸水平降低，这与吲哚胺2,3-双加氧酶活性增加一致。
