2011-05-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656543摘要：敗血症起因於宿主對入侵生物感染的先天免疫反應。敗血症死亡率居高不下，死因多為多重器官衰竭，故需將目前醫學知識應用於早期診斷、辨識高風險病人及病程監測，亦即需更好的生物標記。目前生物標記對敗血症一般多用單一標記，但皆面臨困難，起因於臨床表現分歧。另一研究方式利用整體策略將所有可測得的分子或代謝物質進行同步大規模分析，亦即代謝體研究。該方式已廣為應用於系統性生物學研究。利用質子核磁共振譜儀分析以及液態色層分析合併質譜儀，得知生物代謝體資料及其改變。用於生物液體如血清，可針對敗血症這類全身性反應進行分析，具有很高研究及臨床應用潛能，能瞭解小分子代謝物的結構組成，並具快速而較低成本的特性。此門研究中，呼氣凝集液(EBC)分析屬新興領域，即呼氣體學，以收集呼出氣體冷凝所得液體進行代謝體分析。雖尚未如血液代謝體研究普遍，牽涉生化過程相當複雜，所含分子包括揮發性及不揮發性分子。本計畫目標在利用 EBC 為研究樣本，代謝體分析為工具，試圖瞭解敗血症病人EBC中是否能尋得合適的生物標記，分析分子是否可預測敗血症病人發生多重器官衰竭。計畫分三年執行，逐步建立EBC 收集處理、分析及資料整合作業，預計建立敗血症EBC 生物標記應用模式。<br> Abstract: Sepsis, defined as infection plus systemic manifestations of infection, is a complex anddisastrous clinical syndrome resulting from host innate immune response to invasive infection.Despite advances in resuscitation, its mortality rate remains high, mainly due to multi-organfailure. The need has emerged for translation of current knowledge into practice such asearlier diagnosis, more accurate identification of patients at risk and reliable monitoring ofpatients with sepsis and its sequelae; that is, we need reliable biomarkers.There are different approaches for biomarker identification and evaluation. For sepsis, anumber of biomarkers have been advocated in the clinical field, such as endotoxin, TNF-α,IL-6, C-reactive protein, procalcitonin, etc., but it has remained very difficult to use one oremore of these biomarkers, because of apparent heterogeneity of patients in presentation andresponse to treatment. More holistic approaches involve techniques for simultaneousdetection of variation in transcript, protein or metabolite levels have lead to the application ofgenome-wide searches, including the metabolomics.Metabolomics analysis now is a well-developed platform for researches in systemsbiology, using high-throughput screening processes in clinical diagnosis. It aims at detectingand using holistic metabolic patterns. Proton nuclear magnetic resonance (1H NMR)spectroscopy and liquid chromatography combined with mass spectrometry (LC/MS) havebeen applied for detecting changes in metabolic profiles. Importantly, 1H NMR spectroscopicanalysis of biofluids, such as serum, may offer a high potential for the understanding ofbiochemical processes associated with sepsis, and may provide information on both thestructure and the composition of low-molecular-mass metabolites in biological fluids, and is arapid and low-cost technique for exploring pathological metabolic processes.Exhaled breath condensate (EBC) may be a promising candidate for analysis ofmetabolomics in sepsis, besides the most widely used serum. Nevertheless, it is very complexfor analysis, involving signals originating from hundreds of metabolites. Breath chemical testsrange from exhaled gas measurement to volatile organic compound determination andnonvolatile biomarker profiling in exhaled breath condensate. Exhaled breaths containthousands of volatile and nonvolatile compounds in trace amounts. Sampling of the breathmay allow clinicians and researchers to assess the effect of mitochondrial dysfunction on themetabolism of lung and respiratory tract in septic patients. Through the advancedtechnologies in proteomics, metabolomics, GC/LC-MS, and pattern recognition computation,exhaled biomarker profiling could be performed to generate “breathomics”.The current 3-year proposal is aimed to establish the breathomic profiling of EBC inpatients with sepsis and to evaluate the value of breathomic profiling as a predictor fordevelopment of multi-organ failure in patients with sepsis.敗血症代謝體學吐氣濃縮液Sepsismetabolomicsexhaled breath condensate