A BREATH TEST FOR HEART TRANSPLANT REJECTION

背景：呼吸试验可为心脏移植排斥反应提供一种无创检测方法。排斥反应引起心肌中氧自由基（OFR）活性增加，通过脂质过氧化降解膜，产生挥发性有机化合物（VOCs），并在呼吸中排出。第一阶段研究设计：213例心脏移植患者在预定的心内膜心肌活检当天进行呼吸测试。两名病理学家独立评定排斥程度。呼气挥发性有机化合物采用气相色谱法和能谱法测定。1期研究结果：心脏移植受者的氧化应激增加。呼吸测试对需要治疗的患者具有高度敏感性和特异性（活检结果为II级和III级排斥反应）。实验计划：7个学术医疗中心1656例心脏移植患者呼吸试验的敏感性和特异性。将对7个学术医疗中心的1656名心脏移植患者的排斥反应进行重新评估。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，呼吸测试的广泛应用可以识别出心脏移植受者有很高的排斥风险。这项检查可以大大减少每年进行的心内膜活组织检查的次数，从而降低死亡率、发病率和手术的保健费用。提出的商业应用：呼吸测试可以为心脏移植排斥反应的早期检测提供一种无创的新工具，并减少常规心内肌活检的需要。

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.