Expired CO2/O2 Analysis to Diagnose Pulmonary Embolism

过期 CO2/O2 分析诊断肺栓塞

• 批准号: 7429742
• 负责人: JEFFREY A KLINE
• 金额: $ 35.25万
• 依托单位: BREATHQUANT MEDICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7429742
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Adenocarcinoma; Age; Agreement; Alveolar; Alveolus; Anesthesia procedures; Angiography; Area; Bilateral oophorectomy; Biological Assay; Blood; Blood Vessels; Blood flow; Breathing; Carbon Dioxide; Catheters; Cessation of life; Chest; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Colectomy; Communicable Diseases; Condition; Connective Tissue; Connective Tissue Diseases; Cystectomy; Data; Devices; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diagnostic Specificity; Disease; Embolism; Environmental air flow; Exhalation; Fibrin fragment D; Focal Infection; Fracture; Funding; Gases; Goals; Hand; Hemodialysis; Hip region structure; Hospitalization; Hysterectomy; Image; Inferior; Inflammatory; Invasive; Lung; Malignant Neoplasms; Measurement; Measures; Methodology; Methods; Monitor; Myocardial Infarction; Nephrectomy; Operative Surgical Procedures; Orthopedics; Outcome; Ovariectomy; Pancreatectomy; Partial Pressure; Pathway interactions; Patients; Perfusion; Phase; Phlebography; Physicians; Physiology; Plasma; Postoperative Period; Pregnancy; Pulmonary Embolism; Range; Receiver Operating Characteristics; Reference Standards; Research; Research Design; Risk; Role; Sample Size; Sampling; Sensitivity and Specificity; Sepsis Syndrome; Side; Specificity; Spinal; Staging; Stress; Stroke; Testing; Thromboembolism; Trauma; Venous; Week; adjudicate; cancer surgery; capsule; day; deep vein; diagnostic accuracy; follow-up; knee replacement arthroplasty; monitoring device; novel diagnostics; point of care

DESCRIPTION (provided by applicant): A rapid, noninvasive, and accurate, point-of-care device to diagnose and exclude pulmonary embolism (PE) remains an unmet need, especially for patients with conditions that activate inflammatory and coagulation pathways and therefore predispose to PE. These conditions include surgery, cancer, age >70 years, prolonged hospitalization, hemodialysis, connective tissue and infectious diseases. In patients with these conditions, the quantitative blood D-dimer assay consistently shows a diagnostic specificity below 25% for PE, thus limiting its usefulness as a rule-out test in the patients who engender the most worry for PE. Although many diseases elevate the D-dimer, few diseases besides PE obstruct blood flow to large volumes of alveoli. The novel diagnostic device, the Carboximeter(r), measures the effect of high-ventilation, low-perfusion mismatch from PE on the composition of exhaled breaths. The central hypothesis states that the instantaneous ratio of the expired partial pressure of CO2/O2 at the end of the alveolar phase of steady- state tidal breathing (Carboximetry(r)) will accurately discriminate patients with PE from patients who have other conditions that mimic PE. Three prior clinical trials of 370 patients (n=77 PE+) have demonstrated that the CO2/O2 ratio >0.45 has diagnostic sensitivity and specificity at least equivalent to the quantitative D-dimer <500 ng/mL. In symptomatic post-surgical patients, we hypothesize that Carboximetry will be especially useful to monitor for PE if the CO2/O2 ratio could be compared with preoperative measurements: a minimal change in this ratio would suggest absence of PE whereas a significant decrease would suggest PE. Therefore, in phase I, we will measure the pre- and post-operative CO2/O2 ratio and quantitative D-dimer in 100 high-risk orthopedic and oncological surgery patients. Patients will be followed prospectively to establish outcome with respect to diagnosis of PE. The specific aim is to measure variability caused by anesthesia-surgery on the ratio. If the coefficient of variability (CV) for the CO2/O2 ratio is substantially less than the CV for the D-dimer in patients without PE, this will provide initial evidence that Carboximetry can be used as a monitoring device for PE in high-risk surgical patients. In phase II, we will directly test the diagnostic accuracy of the CO2/O2 ratio versus the quantitative D-dimer in 350 symptomatic patients with conditions known to predispose to PE and elevate the D-dimer. All patients in phase II will undergo CT angiography-venography and 30 day follow-up. Sample size is computed to test the hypothesis of diagnostic equivalence between Carboximetry and the quantitative D-dimer for the area under the receiver operating characteristic (ROC) curve. Secondary analysis of phase II will test if the combination of either a CO2/O2 ratio >0.45 or a D-dimer <500 ng rules out PE with sensitivity >98% and specificity >50%. These highly feasibly specific aims will provide background data needed to establish Carboximetry as a viable alternative or adjunct to the D-dimer to screen for PE in high-risk patients. The condition of clots in the lung, termed pulmonary embolism (PE), is the second leading cause of sudden, unexpected death in the U.S. Physicians lack a quick, accurate method to diagnose and exclude PE at the bedside, especially in patients at risk for PE. This project will fund a clinical study designed to test the diagnostic accuracy of a hand- held breath device that detects the altered gas exchange physiology caused by PE in post-surgical and other patients at high risk for PE.

描述（由申请人提供）：一种快速，无创，准确的护理设备来诊断和排除肺栓塞（PE）仍然是未满足的需求，尤其是对于激活炎症和凝结途径并因此倾向于PE的患者而言。这些疾病包括手术，癌症，> 70岁，住院时间长，血液透析，结缔组织和传染病。在患有这些疾病的患者中，定量血液D-二聚体测定始终显示出PE低于25％的诊断特异性，从而限制了其在对PE最担心的患者中作为规则外测试的有用性。尽管许多疾病升高了D-二聚体，但除了PE以外，很少有疾病阻碍血液流向大量肺泡。新型的诊断装置，羧表仪（R），测量了高通风，PE的低渗透不匹配对呼气呼吸的组成的影响。中央假设指出，在稳态潮汐呼吸的肺泡相结束时，二氧化碳二氧化碳的瞬时比率（羧酸含量（R））将与患有其他模仿PE的患者准确区分患者的PE患者。 370例患者（n = 77 PE+）的三项先前的临床试验表明，CO2/O2比率> 0.45具有诊断敏感性和特异性，至少与定量的D-二聚体<500 ng/mL。在有症状的手术后患者中，我们假设如果可以将CO2/O2的比率与术前测量值进行比较，则羧酸法对于监测PE特别有用：该比率的最小变化表明缺乏PE，而显着降低会表明PE。因此，在第一阶段，我们将在100个高危骨科和肿瘤手术患者中测量术前和术后CO2/O2比和定量D-二聚体。前瞻性遵循患者，以确定PE的诊断结果。具体目的是衡量由该比率麻醉性手术引起的变异性。如果CO2/O2比率的可变性系数（CV）大大低于没有PE的患者的D-二聚体的CV，则这将提供最初的证据，表明羧酸含量可以用作高风险的高风险术患者PE的监测装置。在第二阶段，我们将直接测试350名有症状的患者中CO2/O2比的诊断准确性与定量D-二聚体的诊断准确性，该患者患有易感性和升高D-二聚体的疾病。 II期中的所有患者将进行CT血管造影术和30天的随访。计算样本量以测试羧化学与接收器操作特征（ROC）曲线下区域的定量D-二聚体之间诊断对等的假设。 II期的二级分析将测试CO2/O2比率> 0.45或D-Dimer <500 ng的组合，敏感性> 98％和特异性> 50％。这些高度可行的特定目标将提供所需的背景数据，以建立羧化学作为可行的替代方案或D-Dimer的辅助，以筛选高危患者的PE。肺中凝块的状况称为肺栓塞（PE），是美国医生突然，意外死亡的第二大主要原因，缺乏快速，准确的方法来诊断和排除PE在床边，尤其是在有PE风险的患者中。该项目将资助一项临床研究，旨在测试手持式呼气设备的诊断准确性，该设备检测PE在手术后和其他患者高风险的患者中PE引起的气体交换生理的改变。

项目成果

Leukocyte expression of heme oxygenase-1 [hmox1] varies inversely with severity of tricuspid regurgitation in acute pulmonary embolism.

血红素加氧酶-1 [hmox1] 的白细胞表达与急性肺栓塞中三尖瓣反流的严重程度成反比。

• DOI: 10.1016/j.thromres.2015.08.017
• 发表时间: 2015
• 期刊: Thrombosis research
• 影响因子: 7.5
• 作者: Kline,JeffreyA;Steuerwald,NuryM;Watts,JohnA;Courtney,Mark;Bonkovsky,HerbertL
• 通讯作者: Bonkovsky,HerbertL

Impact of anaesthesia-surgery on D-dimer concentration and end-tidal CO2 and O2 in patients undergoing surgery associated with high risk for pulmonary embolism.

麻醉手术对肺栓塞高风险手术患者 D-二聚体浓度以及呼气末 CO2 和 O2 的影响。

• DOI: 10.1111/j.1475-097x.2008.00789.x
• 发表时间: 2008
• 期刊: Clinical physiology and functional imaging
• 影响因子: 1.8
• 作者: Kline,JeffreyA;Hogg,MelanieM;Mauerhan,DavidR;Frick,StevenL
• 通讯作者: Frick,StevenL