VOLATILE MARKERS OF PULMONARY TUBERCULOSIS IN THE BREATH

描述(申请人提供)：背景：肺结核是一个日益严重的公共卫生问题，但在疑似疾病的患者中确认诊断通常是昂贵和耗时的。临床医生迫切需要一种更快、更好、更便宜的活动性肺结核筛查测试。理想的肺结核筛查试验应该是高度敏感和特异的，以及快速、廉价和非侵入性的。目前没有一种检测方法满足这些标准：抗酸杆菌痰染色具有较高的特异性但敏感性较差，痰培养具有较高的敏感性，但成本较高且耗时较长。然而，一项第一阶段的试点研究提供了证据，表明对呼气中的挥发性有机化合物(VOCs)进行呼气测试可以提供一种临床上有用的新标志物。呼吸中氧化应激标志物模式识别诊断活动性肺结核的敏感性和特异性分别为94.1%和95.1%。呼气VOCs模糊逻辑分析预测活动性肺结核感染的敏感性为100%，特异性为83.3%。 假设：呼气VOCs检测与模式识别分析或模糊逻辑分析相结合可以提供一种新的肺结核筛查方法，该方法具有高敏感性和特异性，以及快速、廉价和非侵入性。 计划验证这一假设：我们将在一项大型多中心试验中对呼气测试的患者子集进行评估，该试验旨在评估抗体检测分析在检测肺结核中的作用。呼气试验的结果将与结核分枝杆菌痰培养的“金标准”进行比较。呼吸VOCs的模式识别分析和模糊逻辑分析将被用来在训练的患者集中开发预测模型。这些模型将在一组患者中进行评估和比较，以确定呼气测试作为活动性肺结核标志物的敏感性、特异性和预测价值。 长期目标： A.科学性：在更大的受试者群体中验证第一阶段研究的临床结果。 B.技术：开发一种相对便宜、小型化和快速的呼吸测试，适用于护理点筛查。 C.商业：获得食品和药物管理局(FDA)对该设备的批准并将其推向市场。 这项研究的重要性：肺结核病的呼气测试可以以低成本快速发现新感染病例，并通过监测治疗的影响，从而产生重要的临床影响。此外，它还有可能降低由肺结核引起的死亡率和发病率。

DESCRIPTION (provided by applicant): Background: Pulmonary tuberculosis (TB) is a growing public health problem, but confirming the diagnosis in patients with suspected disease is often costly and time-consuming. Clinicians urgently need a screening test for active pulmonary tuberculosis that is faster, better and cheaper. An ideal screening test for pulmonary TB would be highly sensitive and specific as well as rapid, inexpensive and non-invasive. No test in current use fulfills these criteria: sputum staining for acid fast bacilli has high specificity but poor sensitivity, and culturing sputum for Mycobacteria has higher sensitivity, but it is expensive and time consuming. However, a Phase 1 pilot study provided evidence that a breath test for volatile organic compounds (VOCs) in the breath could provide a clinically useful new marker. Pattern recognition analysis of oxidative stress markers in breath identified patients with active pulmonary TB infection with 94.1% sensitivity and 95.1% specificity. Fuzzy logic analysis of breath VOCs predicted active pulmonary tuberculosis infection with sensitivity = 100% and specificity = 83.3%. Hypothesis: A test for breath VOCs combined with pattern recognition analysis or fuzzy logic analysis could provide a new screening test for pulmonary TB that is highly sensitive and specific as well as rapid, inexpensive and non-invasive. Plans to test the hypothesis: We will evaluate the breath test in a subset of patients enrolled in a large multicenter trial designed to evaluate antibody-detection assays in the detection of pulmonary TB. Results of the breath test will be compared to the "gold standard" of sputum culture for M. tuberculosis. Pattern recognition analysis and fuzzy logic analysis of breath VOCs will be employed to develop predictive models in a training set of patients. These models will be evaluated and compared in a test set of patients to determine the sensitivity, specificity and predictive value of the breath test as a marker of active pulmonary TB. Long term aims: a. Scientific: To validate the clinical findings of the Phase 1 study in a larger group of subjects. b. Technical: to develop a comparatively inexpensive miniaturized and rapid breath test suitable for point of care screening. c. Commercial: To obtain Food and Drug Administration (FDA) approval of the device and to market it. Importance of the research: A breath test for pulmonary TB could make an important clinical impact by detecting new infections rapidly at low cost, and also by monitoring the impact of therapy. Also, it could potentially reduce the mortality and morbidity caused by pulmonary TB.