Validation of Point-of-Care Breath Test for Pulmonary TB

肺结核护理点呼吸测试的验证

• 批准号: 8832195
• 负责人: Michael Phillips
• 金额: $ 23.13万
• 依托单位: MENSSANA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-05 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832195
• 关键词: AIDS/HIV problem; Acoustics; Adoption; Africa South of the Sahara; Algorithms; Automobile Driving; Biological Markers; Blinded; Breath Tests; Bronchial Spasm; Bronchitis; Cause of Death; Certification; Cessation of life; Chest; Collection; Communicable Diseases; Cost Analysis; Country; Detection; Developing Countries; Diagnosis; Diagnostic; Diagnostic tests; Disease; Genus Mycobacterium; Goals; Good Clinical Practice; Healthcare; High Prevalence; In Vitro; Incidence; India; Infection Control; International; Laboratories; Laboratory Diagnosis; Lung diseases; Marketing; Mass Fragmentography; Medical center; Microscopy; Minority Groups; Modeling; Multicenter Studies; Mycobacterium Infections; Mycobacterium tuberculosis; Nucleic Acid Amplification Tests; Operating System; Outcome; Patients; Persons; Phase; Philippines; Pneumonia; Population; Procedures; Pulmonary Tuberculosis; Reporting; Research; Resources; Risk; Sampling; Sensitivity and Specificity; Small Business Innovation Research Grant; Solutions; Specificity; Sputum; Study Subject; Surface; System; Testing; Time; Training; Tuberculosis; Validation; World Health Organization; base; case finding; cost; cost effective; disability; experience; high risk; phase 1 study; point of care; public health relevance; response; screening; tool; volatile organic compound

 DESCRIPTION (provided by applicant): The problem: Active pulmonary tuberculosis (TB) is a leading cause of death from infectious disease throughout the world. Two billion people, one third of the world's population, are infected with Mycobacterium tuberculosis and 1.6 million died from the disease in 2005. Sputum microscopy and culture remains the mainstay of laboratory diagnosis, accompanied more recently by nucleic acid amplification tests (NAAT). However, sputum culture may require several weeks' incubation, while NAAT is rapid but expensive. An ideal diagnostic test would be sensitive and specific for active pulmonary TB, non-invasive, suitable for use in low- resource countries, faster than sputum culture, and less expensive than NAAT. A new solution to the problem: Mycobacteria manufacture unique volatile organic compounds (VOCs) as metabolites in vitro. A sensitive breath test employing gas chromatography-mass spectrometry (GC-MS) identified VOC biomarkers of active pulmonary TB similar to VOC metabolites of M. tuberculosis detected in vitro. BreathLink is a new point-of-care breath test employing GC with surface acoustic wave detection (GC- SAW), and it delivers results in six minutes. In a multicenter study in India, UK, and the Philippines, BreathLink identified active pulmonary TB with 98% sensitivity and 50% specificity. The high sensitivity of the BreathLink suggests that it could be used as a "rule out" test to identify the majority without TB. Experimental plans: BreathLink will be validated at medical centers in India and the Philippines for its ability to "rule out" subjects who are not infected with active pulmonary TB. I the Phase I (unblinded) study, the "rule out" cutoff points will be validated by comparison to the outcomes of chest x-ray and with sputum testing with microscopy, culture and NAAT. In the Phase II blinded study, a larger study will be performed with view to confirming the efficacy of BreathLink as a screening "rule out" test for active pulmonary TB. Potential impact of the research: If confirmed as effective, a "rule out" breath test could reduce the current high cost of finding new cases of active pulmonary TB, and dramatically reduce the deaths and disabilities that TB now causes in high-burden countries where health care dollars are scarce.

 描述（由申请人提供）： 问题：活动性肺结核 (TB) 是全世界传染病死亡的主要原因。 20 亿人（占世界人口的三分之一）感染了结核分枝杆菌，2005 年有 160 万人死于该病。痰镜检查和培养仍然是实验室诊断的支柱，最近还伴随着核酸扩增检测 (NAAT)。然而，痰培养可能需要数周的培养时间，而 NAAT 速度快但价格昂贵。理想的诊断测试应对活动性肺结核敏感且特异、非侵入性、适合在资源匮乏国家使用、比痰培养更快、比 NAAT 便宜。该问题的新解决方案：分枝杆菌在体外制造独特的挥发性有机化合物（VOC）作为代谢物。采用气相色谱-质谱 (GC-MS) 进行的灵敏呼气测试鉴定出活动性肺结核的 VOC 生物标志物，与体外检测到的结核分枝杆菌的 VOC 代谢物相似。 BreathLink 是一种新型护理点呼气测试，采用 GC 和表面声波检测 (GC-SAW)，可在六分钟内得出结果。在印度、英国和菲律宾进行的一项多中心研究中，BreathLink 识别活动性肺结核的敏感性为 98%，特异性为 50%。 BreathLink 的高灵敏度表明它可以用作“排除”测试来识别大多数人，而无需 结核病。实验计划：BreathLink 将在印度和菲律宾的医疗中心得到验证，因为它能够“排除”未感染活动性肺结核的受试者。在第一阶段（非盲）研究中，“排除”截止点将通过与胸部 X 光检查结果以及显微镜、培养和 NAAT 痰液检测结果进行比较来验证。在第二阶段盲法研究中，将进行更大规模的研究，以确认 BreathLink 作为活动性肺结核筛查“排除”测试的功效。研究的潜在影响：如果证实有效，“排除”呼气测试可以降低目前的高成本 发现新的活动性肺结核病例，并在医疗费用匮乏的高负担国家大幅减少结核病造成的死亡和残疾。