A BREATH TEST FOR HEART TRANSPLANT REJECTION

背景：呼气测试可以为心脏移植排斥反应提供一种非侵入性测试。排斥会引起心肌中氧自由基 (OFR) 活性增加，从而通过脂质过氧化作用降解细胞膜，产生挥发性有机化合物 (VOC)，并通过呼吸排出。第一阶段研究设计：在预定的心内膜心肌活检当天对心脏移植患者进行了 213 次呼吸测试。两名病理学家独立对排斥程度进行分级。通过气相色谱法和质谱法测定呼吸挥发性有机化合物。第一阶段研究结果：心脏移植受者的氧化应激增加。呼吸测试对于需要治疗的患者（活检时的 II 级和 III 级排斥反应）具有高度敏感性和特异性。实验计划：七个学术医疗中心的 1656 名心脏移植患者呼吸测试的敏感性和特异性。七个学术医疗中心将重新评估 1656 名心脏移植患者的排斥反应。该研究的长期目标：如果第一阶段的研究结果得到证实，呼气测试的广泛使用可以识别出具有高排斥风险的心脏移植受者。该测试可以大大减少每年进行的心内膜心肌活检的数量，从而降低该过程的死亡率、发病率和医疗费用。拟议的商业应用：呼气测试可以为早期检测心脏移植排斥反应提供一种非侵入性新工具，并减少常规心内膜心肌活检的需要。

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.