A BREATH TEST FOR HEART TRANSPLANT REJECTION

背景：呼吸测试可以为心脏移植排斥反应提供一种非侵入性测试。排斥反应导致心肌中氧自由基（OFR）活性增加，其通过脂质过氧化降解膜，释放挥发性有机化合物（VOC），其在呼吸中排出。1期研究设计：213例心脏移植患者在计划的肌内膜活检当天进行呼吸试验。两名病理学家独立地对排斥反应的程度进行分级。采用气相色谱-质谱联用技术对呼吸中挥发性有机物进行分析。1期研究结果：心脏移植受者的氧化应激增加。呼气泰特对需要治疗的患者（活检时出现II级和III级排斥反应）具有高度敏感性和特异性。实验计划：呼吸试验在7个医学中心1656例心脏移植患者中的敏感性和特异性。将在七个学术医疗中心的1656名心脏移植患者中重新评估排斥反应。这项研究的长期目标是：如果第一阶段的研究结果得到证实，呼吸测试的广泛使用可以识别心脏移植受者的排斥风险。这项测试可以大大减少每年进行的子宫内膜活检的数量，从而降低死亡率，发病率和医疗保健费用的程序。拟议的商业应用：呼吸测试可以为心脏移植排斥反应的早期检测提供一种非侵入性的新工具，并减少常规肌内膜活检的需要。

Background: Breath testing may provide a non-invasive test for heart transplant rejection. Rejection elicits increased oxygen free radical (OFR) activity in the myocardium which degrades membranes by lipid peroxidation, evolving volatile organic compounds (VOCs) which are excreted in the breath. Phase 1 study design: 213 breath test were performed in heart transplant patients on the day of scheduled endomyocardial biopsy. Two pathologists independently graded the degree of rejection. Breath VOCs were assayed by gas chromatography and mas spectroscopy. Phase 1 study results: Oxidative stress was increased in heart transplant recipients. The breath tet was highly sensitive and specific for patients requiring treatment (Grades II and III rejection on biopsy). Experimental plan: The sensitivity and specificity of the breath test for heart trans in 1656 heart transplant patients at seven academic medical centers. rejection will be reevaluated in 1656 heart transplant patients at seven academic medical centers. The long-term aim of the research: If the Phase I findings are confirmed, widespread use of the breath test could identify heart transplant recipients at high risk of rejection. This test could dramatically reduce the number of endomyocardial biopsies performed every year, thereby reducing the mortality, morbidity and health-care costs of the procedure. PROPOSED COMMERCIAL APPLICATIONS: Breath testing could provide a non-invasive new tool for the early detection of heart transplant rejection, and reduce the need for routine endomyocardial biopsy.