Csanky Ezster, Rühl Ralph, Scholtz Beata, Vasko Attila, Takacs Laszlo, Hempel William M
Department of Pulmonology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary.
Electrophoresis. 2009 Apr;30(7):1228-34. doi: 10.1002/elps.200800722.
One-step global profiling of analyte (mRNA, protein, metabolite) biomarkers may soon replace conventional blood and histological/biopsy diagnostics technologies. It is important to establish whether the numerous blood and other body fluid-derived potential novel diagnostics will be sufficiently efficacious and precise to replace, for example, imaging and functional diagnostic tests. Currently, imaging technologies and spirometry are indispensable for the diagnosis and management of chronic obstructive pulmonary disease (COPD). To validate the concept of using body fluid biomarkers in COPD and to address the question of whether biomarker levels correlate with lung function, we measured the level of a number of biologically relevant lipids and metabolites in the bronchoalveolar lavage (BAL) fluid of COPD and control subjects and examined whether these correlate with numeric parameters of lung function. Both the diagnosis and management of COPD rely on costly and labor intensive lung function tests. Thus, there is an imminent need to replace the current diagnostic approaches with simpler clinical assays. As a first step, we demonstrate proof of principle; the correlation of lipid biomarkers as measured by LC-MS with lung function. In the apparently BAL-accessible fluid compartment, the total recovered lipid metabolite amount, particularly prostaglandin D(2) and eicosapentaenoic acid show a remarkable linear correlation with lung function (R(2)>0.7). The study outcome is encouraging for the continuation of the work toward the measurement of lipid metabolite levels in more easily obtainable biological fluids such as sputum, exhaled air condensate, urine and plasma.
对分析物(mRNA、蛋白质、代谢物)生物标志物进行一步式全面分析,可能很快会取代传统的血液及组织学/活检诊断技术。确定众多源自血液和其他体液的潜在新型诊断方法是否足够有效和精确,以取代例如成像和功能诊断测试,这一点很重要。目前,成像技术和肺活量测定法对于慢性阻塞性肺疾病(COPD)的诊断和管理不可或缺。为了验证在COPD中使用体液生物标志物的概念,并解决生物标志物水平是否与肺功能相关的问题,我们测量了COPD患者和对照受试者支气管肺泡灌洗(BAL)液中多种生物学相关脂质和代谢物的水平,并检查这些是否与肺功能的数值参数相关。COPD的诊断和管理都依赖于成本高昂且劳动强度大的肺功能测试。因此,迫切需要用更简单的临床检测方法取代当前的诊断方法。作为第一步,我们证明了原理;通过液相色谱-质谱法测量的脂质生物标志物与肺功能之间的相关性。在明显可通过BAL获取的液体部分中,回收的脂质代谢物总量,特别是前列腺素D(2)和二十碳五烯酸与肺功能呈现出显著的线性相关性(R(2)>0.7)。该研究结果对于继续开展在更容易获取的生物流体(如痰液、呼出气体冷凝物、尿液和血浆)中测量脂质代谢物水平的工作而言是令人鼓舞的。