Cough collection as a replacement for sputum samples for diagnosing Tuberculosis

描述（由申请人提供）：活动性结核病（TB）每年导致约200万人死亡。据估计，全世界每年有930万人患结核病，其中440万人未得到诊断。如果诊断得当，大多数结核病病例是可以得到治疗的。目前，痰痰是诊断结核病最常用的抽样方法。部分患者（儿童和老年人）痰液难以收集，痰证不足的患者（20%）痰液难以收集。痰液还受到口咽菌群、唾液、粘液和细胞碎片的污染，这对诊断的敏感性和特异性产生负面影响，并降低其对治疗决策的影响。Deton的设备通过直接从咳嗽气雾剂中收集空气传播的细菌以进行后续诊断，从而避免了痰样本的所有缺点。所有患者均可咳嗽；因此，可以从整个患者人群中采集样本，包括不能咳痰的患者。此外，咳嗽收集将细菌浓缩在支持脆弱生物体生存的小样本缓冲液中；而痰液浓度（每mL固定细胞数）和培养基不能改变。最后，收集的咳嗽飞沫物质可能不含痰中的各种口咽污染物。第一阶段的目标是：目的1：研究收集的咳嗽样本是否比痰样本具有更高的诊断敏感性和特异性。目标2：改进设备几何形状，以最大限度地提高收集效率，并为实验室和临床评估提供新设计。第一阶段的目标是在第二阶段对该设备进行不同肺部感染的测试，如非结核分枝杆菌感染和社区获得性肺炎。此外，基于第二个原型和患者数据，可以制造出对患者更友好的一次性设备。

DESCRIPTION (provided by applicant): Active Tuberculosis (TB) causes approximately 2 million annual deaths. An estimated 9.3 million people worldwide develop TB every year, of which 4.4 million are undiagnosed. When diagnosed properly, most TB cases can be treated. Currently, sputum expectorate is the most common sampling method used for TB diagnosis. Sputum is difficult to collect from some patients (children and elderly), and is unattainable from ex- pectoration deficient patients ( 20% of patients). Sputum is also contaminated by oropharyngeal flora, saliva, mucus, and cell debris which negatively affects the sensitivity and specificity of diagnostics, and lowers their impact on treatment decisions. Deton's device avoids all the disadvantages of sputum samples by collecting air- borne bacteria directly from cough aerosol for subsequent diagnosis. All patients can produce cough; therefore, samples can be collected from the entire patient population, including patients who cannot expectorate sputum. Furthermore, the cough collection concentrates bacteria in a small sample volume of buffer that supports the viability of fragile organisms; whereas, sputum concentration (fixed number of cells per mL) and medium cannot be altered. Finally, the collected cough droplet material is potentially free of the various oropharyngeal contaminants in sputum. The Phase I aims of the proposed work are: Aim 1: Investigate whether collected cough samples result in higher diagnostic sensitivity and specificity than sputum samples. Aim 2: Improve the device geometry to maximize collection efficiency and machine the new design for lab and clinical evaluations. Phase I aims will enable the testing of the device for different lung infections such as non-tuberculosis mycobacterial infections and community acquired pneumonia in Phase II. Furthermore, a more patient-friendly disposable device can be manufactured based on the second prototype and the patient data.