2011-05-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651750摘要：預測 背景：急性肺損傷是加護病房病患之重要死因。其原因包含：敗血症、吸入性肺炎、全身 性炎症反應、外傷、輸血等。以目前種種加護病房之醫療，對於此疾病之診斷確認及預 後之評估，仍然相當地不準確。持續地尋找新的生物診斷標記及預後因子，對於此類的 病患而言，仍是相當重要的工作。代謝體學為近年來一個新興的研究領域，其為整體而大規模的量測不同生理狀態下 的代謝物濃度分布。目前已有關於各類疾病的研究發現，各種疾病間及治療前後期，身 體之的代謝物分布有明顯的不同，這也顯示代謝體的分析是有相當的潛力成為未來診斷 或治療的方式之一。呼氣濃縮物(exhaled breath condensate, EBC)，也是近年來發展出的非侵襲性檢查方式。冷凝後的呼氣濃縮物含有許多易揮發或非揮發物質，利用代謝體學、質譜儀等相關 技術，可以檢測出其中有意義之生物標記；先前廣泛被應用的例子為利用呼氣中之一氧 化氮濃度來評估氣喘患者氣喘控制的程度好壞。我們希望經由呼氣濃縮物的代謝體研究，可以幫助我們了解急性肺損傷病患治療前 後的代謝物分佈異同，從中找出有意義的生物標記，以提供未來一個非侵襲性的診斷及 預後評估的方法。方法：在3年内，收集300名接受人工呼吸器之呼吸衰竭患者之呼氣濃縮物，進行代謝體 分析。藉由這些病患的各種臨床資訊與代謝體之分析，從中找出得以幫助診斷或預後的 生物標記。<br> Abstract: Introduction and BackgroundAcute lung injury (ALI) is one of the leading causes of mortality and morbidity in the intensive care unit. The causes of ALI differ from patient to patient, including sepsis, aspiration, systemic inflammation, trauma, blood transfusion, etc. With early detection and treatment, the survival rate may improve significantly. However, it is often difficult to differentiate ALI from cardiogenic pulmonary edema or other causes, even with advanced and invasive tools. A potential tool is the breath chemical test, ranging from exhaled gas measurement, such as exhaled nitric oxide or carbonic monoxide, to volatile organic compound determination and nonvolatile biomarker profiling. Being completely noninvasive, sampling of the exhaled breath condensates (EBC) allows clinicians and researchers to assess body functions in an easier and flexible manner. Exhaled breath contains thousands of volatile and nonvolatile compounds in trace amounts. Therefore, it is not until recently, after the development of highly sensitive cutting-edge technologies in sample analysis, that the evaluation of this type of human specimens becomes possible. Advanced technologies in proteomics, metabolomics, GC/LC-Mass Spectrometry and pattern recognition computation generate a field of exhaled biomarker profiling, called “breathomics” The current proposal is aimed to establish the metabolomic profiling of EBC in patients with ALI in order to setup a useful noninvasive tool for ALI detection, which will then guide the therapy and predict the outcome.MethodsThree hundred of patients with the diagnosis of acute hypoxemic respiratory failure will be recruited. EBC will be collected on the first day, 2 weeks and 4 weeks, respectively. In this study, we chose a comprehensive metabolomic approach by using three distinct mass based analytical methods to examine the complement of small molecules, including primary and secondary metabolites up to 1500Da in size, in the biological samples. Recent advances in column technology, such as hydrophilic interaction chromatography (HILIC) coupled to electrospray mass spectrometry (ESI-MS), allow the detection of highly polar compounds that also occur in biological fluid. Analytical platforms used in this study include 2D*GC-TOF, RP-UHPLC-TOF, and HILIC-UHPLC-TOF. Reproducibility of the LC-TOF and GC-TOF data will be tested by randomized the order of plasma specimens split before measurement with unique identification numbers and proceed for measurement.AimsMetabolomics and clinical data will be correlated to find specific markers and patterns for the disease diagnosis, severity stratification and outcome prediction. Finally, the resulted will be validated on another group of test patients.急性肺損傷呼氣濃縮物代謝體學呼氣體學acute lung injurybreathomicsmetabolomicsexhaled breath condensate