Physiologic Predictors of Respiratory Failure in Patients Presenting with Dyspnea

呼吸困难患者呼吸衰竭的生理预测因素

• 批准号: 10606999
• 负责人: William Cameron McGuire
• 金额: $ 8.33万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10606999
• 关键词: Accident and Emergency department; Acute Respiratory Distress Syndrome; Address; Air; Alveolar; Animal Experiments; Brain; Breathing; COVID-19 pandemic; COVID-19 patient; Cannulas; Clinical; Cohort Studies; Critical Illness; Data; Deterioration; Devices; Dyspnea; Equipment; Gases; Hospitalization; Impairment; Individual; Injections; Intervention; Intubation; Laboratories; Life Support Systems; Literature; Longitudinal Studies; Lung; Lung diseases; Measurement; Mechanical ventilation; Mechanics; Medical; Nose; Outcome; Oxygen; Oxygen Therapy Care; Pathogenesis; Pathology; Patient Triage; Patients; Physiological; Physiology; Predictive Value; Probability; Productivity; Prognosis; Randomized, Controlled Trials; Research Design; Respiratory Failure; Respiratory Muscles; Respiratory physiology; Risk; SARS-CoV-2 infection; Salicylic Acids; Shortness of Breath; Stress; Structure of parenchyma of lung; Symptoms; Techniques; Testing; Therapeutic; Tidal Volume; Traction; Training; Vaccines; Viral Respiratory Tract Infection; career; cisterna magna; cohort; experience; high risk; human data; in vivo; lung injury; lung pressure; meter; millisecond; murine nodule inducing virus; novel; pandemic disease; point of care testing; pressure; prevent; prognostication; progression risk; respiratory; supplemental oxygen; theories; tool; ventilation; Accident and Emergency department; Acute Respiratory Distress Syndrome; Address; Air; Alveolar; Animal Experiments; Brain; Breathing; COVID-19 pandemic; COVID-19 patient; Cannulas; Clinical; Cohort Studies; Critical Illness; Data; Deterioration; Devices; Dyspnea; Equipment; Gases; Hospitalization; Impairment; Individual; Injections; Intervention; Intubation; Laboratories; Life Support Systems; Literature; Longitudinal Studies; Lung; Lung diseases; Measurement; Mechanical ventilation; Mechanics; Medical; Nose; Outcome; Oxygen; Oxygen Therapy Care; Pathogenesis; Pathology; Patient Triage; Patients; Physiological; Physiology; Predictive Value; Probability; Productivity; Prognosis; Randomized, Controlled Trials; Research Design; Respiratory Failure; Respiratory Muscles; Respiratory physiology; Risk; SARS-CoV-2 infection; Salicylic Acids; Shortness of Breath; Stress; Structure of parenchyma of lung; Symptoms; Techniques; Testing; Therapeutic; Tidal Volume; Traction; Training; Vaccines; Viral Respiratory Tract Infection; career; cisterna magna; cohort; experience; high risk; human data; in vivo; lung injury; lung pressure; meter; millisecond; murine nodule inducing virus; novel; pandemic disease; point of care testing; pressure; prevent; prognostication; progression risk; respiratory; supplemental oxygen; theories; tool; ventilation

Project Summary Presentations of respiratory failure can vary from mild requiring supplemental oxygen to more severe requiring invasive mechanical ventilation (i.e., acute respiratory distress syndrome or ARDS). Early in respiratory failure patients often have abnormalities in gas exchange, control of breathing, and/or pulmonary mechanics. During the ongoing COVID-19 pandemic, some studies have demonstrated that increased respiratory drive is associated with worse clinical outcomes while others have demonstrated contrary findings. We have also demonstrated that a noninvasive assessment of gas exchange using the alveolar gas meter (AGM) is predictive of who will require supplemental oxygen from COVID-19 infection. Additional studies predating the COVID-19 pandemic showed that increased inspiratory effort, large transpulmonary pressure changes, and elevated dead space were all associated with worse outcomes in ARDS. However, many of these studies focused on patients already intubated and mechanically ventilated. Less is known about the relevance of these parameters in spontaneously breathing individuals. For a few years now the notion of patient self-inflicted lung injury (P-SILI) has been gaining traction in the medical literature. The basic concept is that patients with impending respiratory failure from existing lung injury can cause worsening damage to their lungs. If patients are spontaneously breathing with excessively high respiratory drive, then they may generate excessively negative inspiratory efforts leading to major transpulmonary pressure changes. The results of these abnormalities are large tidal volumes like mechanically ventilating someone with injurious tidal volumes prior to the advent of low tidal volume ventilation (LTVV). Also, retrospective review of large cohort studies and randomized controlled trials of ARDS patients have demonstrated that spontaneously breathing patients prior to intubation often generated excessively large tidal volumes. Whether their subsequent lung injury was entirely due to their underlying ARDS pathology or partially due to superimposed P-SILI is not known. If a physiological signature of impending respiratory failure in spontaneously breathing individuals exists and it is associated with elevated respiratory drive, steps can subsequently be taken to mitigate the increased drive and study the longitudinal effects of these variables in patients who develop respiratory failure. Moreover, if such a signature exists and intervention abrogates some of the subsequent lung injury, this is a strong proof of concept for P-SILI in vivo. We aim to test three independent but related hypotheses. First, the AGM is a novel and simple technique which can be used to identify patients at increased risk for respiratory failure better than traditional metrics. Second, the breath hold maneuver is a validated technique to assess control of breathing that can identify patients with poor respiratory prognosis. Third, the airway occlusion pressure will provide additional predictive value in identifying high risk patients. This proposal will lay the groundwork for the PI to gain experience and training for a long and productive academic medical career.

项目摘要 呼吸衰竭的表现可能从需要补充氧气到更严重 需要侵入性的机械通气（即急性呼吸窘迫综合征或ARDS）。早期 呼吸衰竭患者通常在气体交换，呼吸控制和/或肺部有异常 力学。在正在进行的COVID-19大流行期间，一些研究表明，增加了 呼吸驱动与临床结果较差有关，而其他呼吸驱动则表现出相反的发现。 我们还证明了使用肺泡气表对气体交换的无创评估 （AGM）可以预测谁将需要从COVID-19感染中补充氧气。其他研究 早于199年大流行，表明灵感的努力增加，肺上压力很大 变化和升高的死空间都与ARDS的结果差有关。但是，很多 这些研究的重点是已经插管和机械通风的患者。对 这些参数在自发呼吸中的相关性。几年来 患者自我造成的肺损伤（P-SILI）一直在医学文献中受到关注。基本概念是 现有肺损伤呼吸衰竭的患者可能会导致对其的损害恶化 肺。如果患者自发呼吸呼吸驱动过高，则可能会产生 过度负面的鼓舞性努力导致重大的转肺压力变化。结果 这些异常是大潮汐量，例如机械通风有害的潮汐量的人 在低潮汐音量通风（LTVV）出现之前。此外，对大型队列研究和 ARDS患者的随机对照试验表明，自发呼吸患者之前 插管通常会产生过多的潮汐体积。他们随后的肺部受伤是否是 完全是由于其潜在的ARDS病理或部分原因是由于叠加的p-sili所致。如果a 自发呼吸个体的呼吸衰竭的生理特征存在，这是 与升高呼吸道驱动有关，随后可以采取步骤来减轻驱动器的增加和 研究这些变量对发生呼吸衰竭的患者的纵向影响。而且，如果这样 签名存在和干预废除了随后的一些肺损伤，这是一个有力的证明 p-sili in Vivo的概念。我们旨在检验三个独立但相关的假设。首先，股东大会是一本小说 和简单的技术，可用于识别患者呼吸衰竭风险增加的患者比 传统指标。其次，呼吸保持机动是一种评估呼吸控制的验证技术 可以确定呼吸预后不良的患者。第三，气道阻塞压力将提供 识别高风险患者的其他预测价值。该建议将为PI奠定基础 在长期且富有成效的学术医疗职业中获得经验和培训。