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

机械通气患者下呼吸道感染的无创诊断标志物

• 批准号: 10697471
• 负责人: Dapeng Chen
• 金额: $ 96.75万
• 依托单位: ZETEO TECH, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697471
• 关键词: Address; Affect; Air; Algorithms; Antibiotic Therapy; Antibiotics; Biological Assay; Biological Markers; Breath Tests; Cause of Death; Clinical; Collaborations; Collection; Communicable Diseases; Control Groups; Critical Care; Decision Making; Deterioration; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Early Diagnosis; Early Intervention; Economic Burden; Exhalation; Exposure to; Face; Functional disorder; Future; Healthcare Systems; Hospitals; Human; Individual; Infection; Intensive Care Units; Intubation; Lipids; Literature; Lower Respiratory Tract Infection; Lower respiratory tract structure; Lung infections; Mass Spectrum Analysis; Mechanical Ventilators; Mechanical ventilation; Medical; Methodology; Methods; Outcome; Patients; Peptide Hydrolases; Performance; Phase; Pilot Projects; Polymerase Chain Reaction; Process; Proteins; Proteolysis; Proteomics; Publishing; Risk; Sampling; Sepsis; Septic Shock; Surgical Intensive Care; Symptoms; System; Technology; Testing; Time; Training; Treatment Cost; Work; air sampling; clinical diagnosis; design; diagnostic accuracy; diagnostic biomarker; diagnostic technologies; expectation; experience; high risk; improved; innovation; invention; molecular diagnostics; mortality; multiplex assay; noninvasive diagnosis; novel; novel diagnostics; pathogen; prevent; product development; validation studies; verification and validation

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.

项目摘要/摘要 下呼吸道感染（LRTI）是最常见的感染原因。 LRTI影响患者 在ICU中，尤其是具有机械呼吸机的患者。早期开始短途抗生素 治疗是管理LRTI机械通风患者的基石。但是，使用电流 临床标准，直到下呼吸道感染良好，通常才能对LRTI进行诊断 已确立的。为了解决当前局限性，分子诊断技术（例如聚合酶链） 已经开发了基于反应（PCR）的多重分析。但是，他们无法区分 定植和感染。因此，LRTI需要更复杂的诊断方法 诊断和管理。人类呼气的空气具有巨大的潜力，可以解决当前的局限 诊断LRTI。但是，缺乏适合临床使用的收集系统为 探索使用人类呼出空气的医疗潜力。为了解决这些限制，Zeteo Tech 翻新了捕获机制，并开发了一种新颖的收集系统，Hearthbiomicstm 用于人类呼吸分析的生物分子。具体来说，我们证明了呼吸道可能是 配置为机械呼吸机，用于从插管患者的呼出空气中收集生物分子 重症监护病房。最重要的是，通过使用质谱法来表征这些生物分子，我们 鉴定出截短的蛋白质成型，这是活化蛋白酶的产物，并证明 在一项初步研究中，截短的蛋白质成型型具有LRTI的诊断潜力。考虑到这一证据，我们 提议确定是否可以将截短的蛋白质成型用于人类呼气的空气中 机械通风患者中LRTI诊断和早期预测LRTI的方法。我们的工作会 在很大程度上协助临床医生关于抗生素治疗的决策，并大大改善患者 通过限制抗生素需求并最大程度地减少对不必要的抗生素的有害暴露的临床结果 治疗。