Kramer R, Sauer-Heilborn A, Welte T, Guzman C A, Höfle M G, Abraham W-R
Research Group Chemical Microbiology, Helmholtz Centre for Infection Research (HZI), Inhoffenstrasse 7, 38124, Braunschweig, Germany.
Eur J Clin Microbiol Infect Dis. 2015 Apr;34(4):745-51. doi: 10.1007/s10096-014-2286-5. Epub 2014 Nov 28.
For easy handling and speed of lung diseases diagnostics, approaches based on volatile organic compounds (VOCs), including those emitted by pathogenic microorganisms, are considered but currently require considerable sampling efforts. We tested whether easy-to-handle and fast detection of lung infections is possible using solid-phase microextraction (SPME) of 100 ml of exhaled breath. An analytical procedure for the detection of VOCs from the headspace of epithelial lung cells infected with four human pathogens was developed. The feasibility of this method was tested in a cystic fibrosis (CF) outpatient clinic in vivo. Exhaled breath was extracted by SPME and analyzed by gas chromatography-mass spectrometry (GC-MS). The compositions of VOCs released in the infection model were characteristic for all individual pathogens tested. Exhaled breath of CF patients allowed clear distinction of CF patients and controls by their VOC compositions using multivariate analyses. Interestingly, the major specific VOCs detected in the exhaled breath of infected CF patients in vivo differed from those monitored during bacterial in vitro growth. SPME extraction of VOCs from 100 ml of human breath allowed the distinction between CF patients and healthy probands. Our results highlight the importance of assessing the entire pattern of VOCs instead of selected biomarkers for diagnostic purposes, as well as the need to use clinical samples to identify reliable biomarkers. This study provides the proof-of-concept for the approach using the composition of exhaled VOCs in human breath for the rapid identification of infectious agents in patients with lower respiratory tract infections.
为了便于操作并加快肺部疾病的诊断速度,基于挥发性有机化合物(VOCs)的方法,包括那些由病原微生物释放的化合物,已被考虑,但目前需要大量的采样工作。我们测试了使用固相微萃取(SPME)对100毫升呼出气体进行简单操作和快速检测肺部感染是否可行。开发了一种从感染四种人类病原体的上皮肺细胞顶空中检测挥发性有机化合物的分析程序。该方法的可行性在囊性纤维化(CF)门诊进行了体内测试。呼出气体通过固相微萃取进行提取,并通过气相色谱 - 质谱联用仪(GC - MS)进行分析。在感染模型中释放的挥发性有机化合物的组成对于所有测试的单个病原体来说都是独特的。使用多变量分析,CF患者的呼出气体通过其挥发性有机化合物组成能够清晰地区分CF患者和对照组。有趣的是,在体内感染的CF患者呼出气体中检测到的主要特异性挥发性有机化合物与细菌体外生长期间监测到的不同。从100毫升人体呼出气体中进行固相微萃取挥发性有机化合物,能够区分CF患者和健康受试者。我们的结果强调了评估挥发性有机化合物的整体模式而非选择生物标志物用于诊断目的的重要性,以及使用临床样本识别可靠生物标志物的必要性。本研究为利用人体呼出挥发性有机化合物的组成快速识别下呼吸道感染患者中的感染病原体的方法提供了概念验证。