Zang Xiaoling, Monge María Eugenia, McCarty Nael A, Stecenko Arlene A, Fernández Facundo M
School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
Centro de Investigaciones en Bionanociencias (CIBION), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Godoy Cruz 2390, C1425FQD, Ciudad de Buenos Aires, Argentina.
J Proteome Res. 2017 Feb 3;16(2):550-558. doi: 10.1021/acs.jproteome.6b00675. Epub 2016 Dec 2.
Progressive lung function decline and, ultimately, respiratory failure are the most common cause of death in patients with cystic fibrosis (CF). This decline is punctuated by acute pulmonary exacerbations (APEs), and in many cases, there is a failure to return to baseline lung function. Ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry was used to profile metabolites in exhaled breath condensate (EBC) samples from 17 clinically stable CF patients, 9 CF patients with an APE severe enough to require hospitalization (termed APE), 5 CF patients during recovery from a severe APE (termed post-APE), and 4 CF patients who were clinically stable at the time of collection but in the subsequent 1-3 months developed a severe APE (termed pre-APE). A panel containing two metabolic discriminant features, 4-hydroxycyclohexylcarboxylic acid and pyroglutamic acid, differentiated the APE samples from the stable CF samples with 84.6% accuracy. Pre-APE samples were distinguished from stable CF samples by lactic acid and pyroglutamic acid with 90.5% accuracy and in general matched the APE signature when projected onto the APE vs stable CF model. Post-APE samples were on average more similar to stable CF samples in terms of their metabolomic signature. These results show the feasibility of detecting and predicting an oncoming APE or monitoring APE treatment using EBC metabolites.
进行性肺功能下降以及最终的呼吸衰竭是囊性纤维化（CF）患者最常见的死亡原因。这种下降以急性肺部加重（APE）为特征，并且在许多情况下，肺功能无法恢复到基线水平。采用超高效液相色谱四极杆飞行时间质谱法对17例临床稳定的CF患者、9例因APE严重到需要住院治疗的CF患者（称为APE组）、5例从严重APE恢复过程中的CF患者（称为APE后组）以及4例采集时临床稳定但在随后1 - 3个月内发生严重APE的CF患者（称为APE前组）的呼出气冷凝物（EBC）样本中的代谢物进行分析。一个包含4 - 羟基环己基羧酸和焦谷氨酸这两种代谢判别特征的检测组，以84.6%的准确率区分了APE样本和稳定CF样本。乳酸和焦谷氨酸以90.5%的准确率区分了APE前样本和稳定CF样本，并且在投影到APE与稳定CF模型上时，APE前样本总体上与APE特征相符。APE后样本在代谢组学特征方面平均与稳定CF样本更相似。这些结果表明，利用EBC代谢物检测和预测即将发生的APE或监测APE治疗具有可行性。
