2016-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/704914摘要：急性呼吸窘迫症候群(Acute respiratory distress syndrome, ARDS)是一種因系統性發炎造成微血管通透性增加，而導致肺水腫及肺傷害的疾病，急性呼吸窘迫症候群會造成肺部的順應性(Compliance)及氣體交換(Gas exchange)的嚴重損害，致死率極高。即便重症醫療技術在過去數十年已有長足的進步，急性呼吸窘迫症候群的死亡率仍高達30-40%。過去的研究顯示，急性呼吸窘迫症候群並非單一表現型疾病，而是在治療反應、臨床進程、及預後方面存在很大的異質性(Heterogeneity)，這些異質性被認為是過去臨床試驗在研究各種 ARDS 治療時，無法看出治療成效的原因之一，若欲改善 ARDS的治療成效及找出各種 ARDS 處置的適切治療對象，則首先必須對 ARDS 的臨床表現型(Phenotype)及異質性有更清楚的描述及研究。歐美 ARDS 聯合會議提議使用 GOCA system (Gas exchange, Organ failure, Cause, Associated diseases)來定義 ARDS 的表現型及異質性，但目前相關的研究仍然未有進展。此外，致病因(Etiology)是 ARDS 臨床表現發生異質性一個重要的因素，但致病因及疾病自然史的資料多來自於年代較久遠的研究。隨著近年來醫學處置的演進、人口老化、共病症增加、及新興呼吸道傳染病盛行等因素的影響，ARDS 的致病因及臨床病程可能已有相當大的改變。欲了解目前ARDS 的致病因及表現型，以及兩者所建構出的異質性，本研究欲透過一多中心的觀察性研究，提供 ARDS 致病因及呼吸生理表現型的完整資料，並依據致病因及呼吸生理的序列變化，希望能找出各 ARDS subgroups 適合的 ARDS 處置。此外，因應近年來流感病毒的盛行，流感相關的 ARDS 次族群亦會做特別分析。 第一年的研究計畫，將建立一網路登錄平台以利多個收案地點進行資料登錄，所有的嚴重低血氧(PaO2/FiO2 ≦ 300)呼吸衰竭的個案，包括 ARDS 及 non-ARDS 者皆會納入篩檢及追蹤，以利評估目前 ARDS 及 non-ARDS 之臨床進程及預後，而符合ARDS 定義者將在取得同意書後，進行 Etiology 診斷評估步驟，其中包含呼吸道檢體病毒檢測等步驟。 第二年的計畫除延續第一年的流行病學研究外，將更廣泛測量呼吸生理參數，測試對不同 PEEP 時的呼吸生理參數變化，並與胸部電腦斷層影像之表現型做相互對照。 第三年的計畫旨在擴大收案數目及範圍，並收入外部他院個案以驗證內部所得的研究數據。且在累積 2 年的個案數之後，將可評估各種 ARDS 治療的效益及併發症，以及在各個 ARDS 表現型中是否有不同的效果，研究的結果將有利進行下一步的臨床試驗，此外，也可利用多年的資料來了解 ARDS 致病因的季節性變化及流感病毒盛行的影響。 <br> Abstract: Acute respiratory distress syndrome (ARDS) is a consequence of diffuse and inflammatory lung injury that leads to increased pulmonary vascular permeability [1, 2]. It is a life-threatening condition because gas exchange and respiratory compliance are both severely impaired. Despite the advances in critical care medicine over the last decades, the mortality rate for ARDS remains high for around 30 to 40% [3]. Previous studies and clinical trials showed that there is considerable heterogeneity in ARDS regarding response to therapies, clinical course and outcome [4]. The heterogeneity may have contributed to failure to find a true intervention effect in previous clinical trials [4]. To improve the treatment outcomes of ARDS, the phenotypes and heterogeneity of ARDS should be defined before developing tailored therapy. GOCA system (Gas exchange, Organ failure, Cause, Associated diseases) had been proposed by American-European Consensus Conference to evaluate the heterogeneity of ARDS [5]. However, the relevant data are still very limited. In addition, the majority of the data about the inciting cause and clinical course of ARDS are out of date [5-8]. The modern concept of critical care and etiology change due to aging of population, high burden of concomitant comorbidities and emerging respiratory tract infections may have changed the clinical picture of ARDS. In this three-year study, we aimed to evaluate the inciting cause of ARDS in Taiwan and to observe the etiology-specific clinical course and phenotype of respiratory mechanics. These findings will help to find out feasible treatment modalities for specific phenotype of ARDS. The first-year project is intended to establish a web-based registry system and use the pre-defined screening protocol to evaluate the prevalence and burden of severe hypoxemic respiratory failure (PaO2/FiO2 ≦ 300) in modern ICUs. The clinical course and outcomes of ARDS and non-ARDS hypoxemic respiratory failure will be compared. In the meanwhile, a procedure to survey ARDS etiology will be performed. In the second year of the study, the ARDS etiology surveillance and clinical course recording will be continued. Respiratory mechanics including plateau pressure, dead space, static respiratory compliance and minute ventilation will be daily measured. A procedure to test responsiveness to PEEP will be performed [9, 10]. Chest CT imaging will be obtained for correlation analysis [11]. In the third year of the study, the main work is to expand sample size and validate the study findings by including patients outside the original study hospitals. With accumulated data in the previous two years, we can analyze the effects of various interventions for ARDS in each phenotype of ARDS. The data will be important to design tailored therapy for specific phenotype of ARDS and future clinical trials. In addition, the effects of seasonal change on ARDS etiology and the subgroup of influenza-related ARDS will be further evaluated.急性呼吸窘迫症候群流行性感冒病毒表現型呼吸衰竭呼吸力學ARDSinfluenzaphenotyperespiratory distress syndromerespiratory failurerespiratory mechanics