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

项目概要/摘要 下呼吸道感染（LRTI）是最常见的感染性死亡原因。LRTI影响患者 在ICU中更常见，尤其是使用机械呼吸机的患者。早期使用短程抗生素 治疗是管理LRTI机械通气患者的基石。然而，使用当前 根据临床标准，下呼吸道感染的诊断通常要等到下呼吸道感染的症状消失后才能做出。 确立了习为了解决目前的局限性，分子诊断技术，如聚合酶链 已经开发了基于PCR的多重测定。然而，他们无法区分 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。人类呼出的空气有很大的潜力来解决目前的限制， 诊断LRTI。然而，缺乏适合临床使用的收集系统是一个主要障碍 探索人类呼出气体的医学潜力。为了解决这些限制，Zeteo Tech 更新了捕获机制，并开发了一种新的收集系统BreathBiomicsTM， 用于人体呼吸分析的生物分子。具体来说，我们证明了BreathBiomicsTM可以 配置成机械净化器，用于收集插管患者呼出空气中的生物分子， 重症监护室最重要的是，通过使用质谱仪表征这些生物分子， 鉴定了截短的蛋白形式，其是活化蛋白酶的产物，并证明， 在一项初步研究中，截短的蛋白酶体具有诊断LRTI的潜力。考虑到这些证据，我们 建议确定人类呼出气中截短的蛋白质是否可以用作非侵入性的 用于机械通气患者LRTI诊断和早期预测的方法。我们充其量 这在很大程度上有助于临床医生关于抗生素治疗决策， 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来实现临床结局 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.