Airoldi Cristina, Ciaramelli Carlotta, Fumagalli Marco, Bussei Rita, Mazzoni Valeria, Viglio Simona, Iadarola Paolo, Stolk Jan
Department of Biotechnology and Biosciences, University of Milano-Bicocca , 20126 Milan, Italy.
Department of Pulmonology, Leiden University Medical Center , 2333 Leiden, The Netherlands.
J Proteome Res. 2016 Dec 2;15(12):4569-4578. doi: 10.1021/acs.jproteome.6b00648. Epub 2016 Oct 5.
The metabolomic analysis of exhaled breath condensate (EBC) may provide insights on both the pathology of pulmonary disorders and the response to therapy. This pilot study describes the ability of nuclear magnetic resonance (NMR)-based metabolomics to discriminate α1-antitrypsin deficient (AATD)-patients, who were diagnosed with moderate to severe emphysema, from healthy individuals. Comparative analysis of samples from these two homogeneous cohorts of individuals resulted in the generation of NMR profiles that were different from both a qualitative and a quantitative point-of-view. Among the identified metabolites that separated patients from controls, acetoin, propionate, acetate, and propane-1,2 diol were those presenting the biggest difference. Unambiguous confirmation that the two groups could be completely differentiated on the basis of their metabolite content came from the application of univariate and multivariate statistical analysis (principal component analysis, partial least squares discriminant analysis (PLS-DA), and orthogonal PLS-DA). MetaboAnalyst 3.0 platform, used to define a relationship among metabolites, allowed us to observe that pyruvate metabolism is the most-involved pathway, most of metabolites being originated from pyruvate. These preliminary data suggest that NMR, with its ability to differentiate the metabolic fingerprint of EBC of AATD patients from that of healthy controls, has a potential "clinical applicability" in this area.
呼出气冷凝液（EBC）的代谢组学分析可能为肺部疾病的病理学及治疗反应提供见解。这项初步研究描述了基于核磁共振（NMR）的代谢组学区分α1-抗胰蛋白酶缺乏症（AATD）患者与健康个体的能力，其中AATD患者被诊断为中度至重度肺气肿。对这两组同质个体样本的比较分析产生了在定性和定量方面均不同的NMR图谱。在区分患者与对照的已鉴定代谢物中，乙偶姻、丙酸盐、乙酸盐和1,2-丙二醇的差异最大。单变量和多变量统计分析（主成分分析、偏最小二乘判别分析（PLS-DA）和正交PLS-DA）的应用明确证实，两组可根据其代谢物含量完全区分。用于定义代谢物之间关系的MetaboAnalyst 3.0平台使我们能够观察到，丙酮酸代谢是最相关的途径，大多数代谢物都源自丙酮酸。这些初步数据表明，NMR能够区分AATD患者与健康对照的EBC代谢指纹，在该领域具有潜在的“临床适用性”。
