Hagens Laura A, Heijnen Nanon F L, Smit Marry R, Verschueren Alwin R M, Nijsen Tamara M E, Geven Inge, Schultz Marcus J, Bergmans Dennis C J J, Schnabel Ronny M, Bos Lieuwe D J
Department of Intensive Care, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Intensive Care, Maastricht University Medical Center+, Maastricht, The Netherlands.
Ann Transl Med. 2021 Aug;9(15):1262. doi: 10.21037/atm-21-1384.
Acute respiratory distress syndrome (ARDS) is currently diagnosed by the Berlin Definition. Diagnosis is subjective and often late. Untargeted metabolomics analysis of exhaled breath with gas chromatography and mass spectrometry (GC-MS) showed that the breath concentration of octane has a high diagnostic accuracy for ARDS. To facilitate rapid bedside measurement of this biomarker, a point-of-care (POC) breath test was developed. A prototype already showed good reproducibility and repeatability for the detection of octane. In this study we aim to measure octane in exhaled breath of invasively ventilated intensive care unit (ICU) patients and validate the diagnostic accuracy of the breath test for the early diagnosis of ARDS.
This is a multicentre observational cohort study in patients admitted to the ICU receiving invasive ventilation for at least 24 hours. At least 500 patients in two academic hospitals in The Netherlands will be included. ARDS patients will be compared to patients without ARDS. ARDS diagnosis will be based on the Berlin Definition. Two diagnostic assessments will be performed during the first 72 hours of invasive ventilation, including breath sampling, arterial blood gas analysis and lung ultrasound (LUS). In patients fulfilling the criteria for ARDS, three additional breath samples will be taken to assess resolution. The primary endpoint is the diagnostic accuracy for ARDS, defined by the area under the receiver operating characteristics curve (AUROCC) of octane concentration in exhaled breath. Secondary endpoints are the association between exhaled breath octane and ARDS adjusted for confounders, and the added diagnostic accuracy of the breath test on top of the Lung Injury Prediction Score (LIPS).
This is the first study that validates a metabolic biomarker of ARDS in an adequate sample size. The major novelty is the use of a POC breath test that has been specifically developed for the purpose of diagnosing ARDS. Strengths are; assessment in the early phase, in patients at risk for ARDS, longitudinal sampling and an expert panel to reliably diagnose ARDS. This study will provide a decisive answer on the question if exhaled breath metabolomics can be used to diagnose ARDS.
The trial is registered at trialregister.nl (ID: NL8226) with the tag "DARTS".
急性呼吸窘迫综合征（ARDS）目前采用柏林定义进行诊断。诊断具有主观性且往往较晚。采用气相色谱和质谱联用（GC-MS）对呼出气体进行非靶向代谢组学分析表明，呼出气体中辛烷的浓度对ARDS具有较高的诊断准确性。为便于在床边快速检测该生物标志物，开发了一种即时检测（POC）呼气试验。一种原型产品已显示出检测辛烷的良好重现性和重复性。在本研究中，我们旨在测量接受有创通气的重症监护病房（ICU）患者呼出气体中的辛烷，并验证呼气试验对ARDS早期诊断的诊断准确性。
这是一项多中心观察性队列研究，研究对象为入住ICU且接受有创通气至少24小时的患者。荷兰两家学术医院至少500例患者将被纳入研究。ARDS患者将与非ARDS患者进行比较。ARDS诊断将基于柏林定义。在有创通气的前72小时内将进行两次诊断评估，包括呼气采样、动脉血气分析和肺部超声（LUS）。对于符合ARDS标准的患者，将额外采集三份呼气样本以评估病情缓解情况。主要终点是ARDS的诊断准确性，由呼出气体中辛烷浓度的受试者工作特征曲线下面积（AUROCC）定义。次要终点是校正混杂因素后呼出气体辛烷与ARDS之间的关联，以及呼气试验在肺损伤预测评分（LIPS）基础上增加的诊断准确性。
这是第一项在足够样本量下验证ARDS代谢生物标志物的研究。主要创新点是使用了专门为诊断ARDS而开发的POC呼气试验。优点包括：在早期阶段对有ARDS风险的患者进行评估、纵向采样以及由专家小组可靠地诊断ARDS。本研究将对呼出气体代谢组学是否可用于诊断ARDS这一问题给出决定性答案。
该试验已在trialregister.nl（ID：NL8226）注册，标签为“DARTS”。
