Noninvasive Diagnostic Markers of Lower Respiratory Tract Infection in Mechanically Ventilated Patients

项目摘要/摘要 下呼吸道感染(LRTI)是最常见的传染病死亡原因。LRTI影响患者 更多的是在ICU，特别是使用机械呼吸机的患者。早期使用短程抗生素 治疗是治疗下呼吸道感染机械通气患者的基石。但是，使用当前的 根据临床标准，只有在下呼吸道感染良好后才能诊断为下呼吸道感染。 已经成立了。为了解决目前的限制，分子诊断技术，如聚合酶链 基于聚合酶链式反应(PCR)的多重分析已经发展起来。然而，他们不能区分 殖民和感染。因此，需要一种更复杂的诊断方法来诊断LRTI 诊断和管理。人类呼出的空气具有巨大的潜力来解决目前在 诊断LRTI。然而，缺乏合适的临床使用的收集系统给 探索利用人类呼出的空气的医学潜力。为了解决这些限制，齐特奥科技公司 更新了捕获机制，并开发了一种新的收集系统BreathBiomicsTM，用于 用于人体呼气分析的生物分子。具体地说，我们演示了BreathBiomicsTM可以 配置成机械呼吸器，用于收集插管患者呼出的空气中的生物分子 重症监护室。最重要的是，通过使用质谱学来表征这些生物分子，我们 鉴定了截短的蛋白形式，这是激活的蛋白酶的产物，并证明了 在一项先导性研究中，截短的蛋白形式具有诊断LRTI的潜力。考虑到这一证据，我们 建议确定人类呼出空气中截断的蛋白质形式是否可用作非侵入性 机械通气患者下呼吸道感染的诊断及早期预测方法我们的工作是 在很大程度上帮助临床医生做出抗生素治疗的决策，并显著改善患者的 通过限制抗生素需求和最大限度地减少不必要抗生素的有害暴露的临床结果 治疗。

Project Summary/Abstract Lower respiratory tract infection (LRTI) is the most common infectious cause of death. LRTI affects patients more often in ICUs, especially patients with mechanical ventilators. Early initiation of short-course antibiotic therapy is the cornerstone in managing mechanically ventilated patients with LRTI. However, using the current clinical criteria, a diagnosis of LRTI is typically not made until an infection in the lower respiratory tract is well established. To address the current limitations, molecular diagnostic technologies such as polymerase chain reaction (PCR)-based multiplex assays have been developed. However, they cannot distinguish between colonization and infection. Therefore, a more sophisticated diagnostic methodology is needed for LRTI diagnosis and management. Human exhaled air has great potential to address the current limitations in diagnosing LRTI. However, the lack of a suitable collection system for clinical use put a major barrier to exploring the medical potential of using human exhaled air. To address these limitations, Zeteo Tech renovated the capture mechanism and developed a novel collection system, BreathBiomicsTM, for biomolecules for human breath analysis. Specifically, we demonstrated that BreathBiomicsTM could be configured into mechanical ventilators for collecting biomolecules in the exhaled air from intubated patients in intensive care units. Most importantly, by characterizing these biomolecules using mass spectrometry, we identified truncated proteoforms, which are the products of activated proteases, and demonstrated that truncated proteoforms had the diagnostic potential for LRTI in a pilot study. Considering this evidence, we propose to determine whether truncated proteoforms in human exhaled air can be used as a noninvasive method for LRTI diagnosis and early prediction of LRTI in mechanically ventilated patients. Our work would largely assist decision-making for clinicians regarding antibiotic treatment and dramatically improve patients' clinical outcomes by limiting antibiotic requirements and minimizing harmful exposure to unnecessary antibiotic treatment.