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）每年造成约200万人死亡。据估计，全世界每年有930万人患结核病，其中440万人未被诊断。如果诊断正确，大多数结核病病例都可以得到治疗。目前，痰是结核病诊断最常用的采样方法。一些患者（儿童和老年人）的痰液难以收集，并且无法从呼吸困难患者（20%的患者）中获得。痰液还被口咽植物群、唾液、粘液和细胞碎片污染，这对诊断的灵敏度和特异性产生负面影响，并降低它们对治疗决策的影响。迪顿的设备避免了痰样本的所有缺点，直接从咳嗽气雾剂中收集空气传播的细菌，用于随后的诊断。所有患者均可咳嗽;因此，可从整个患者人群（包括不能咳出痰液的患者）中采集样本。此外，咳嗽收集将细菌浓缩在支持脆弱生物体活力的小样本体积缓冲液中;而痰液浓度（每mL固定细胞数）和培养基不能改变。最后，收集的咳嗽液滴物质可能不含痰中的各种口咽污染物。所提出的工作的第一阶段的目标是：目的1：调查收集的咳嗽样本是否导致更高的诊断灵敏度和特异性比痰液样本。目的2：改进器械几何结构，以最大限度地提高收集效率，并对新设计进行机加工，以进行实验室和临床评价。第一阶段的目标是在第二阶段测试该器械用于不同肺部感染，如非结核分枝杆菌感染和社区获得性肺炎。此外，可以基于第二原型和患者数据来制造对患者更友好的一次性装置。

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.