Physiologic Predictors of Respiratory Failure in Patients Presenting with Dyspnea

项目摘要 呼吸衰竭的表现可以从需要补充氧气的轻度到更严重 需要有创机械通气（即，急性呼吸窘迫综合征或ARDS）。年初 呼吸衰竭患者通常具有气体交换、呼吸控制和/或肺功能的异常。 力学在持续的COVID-19大流行期间，一些研究表明， 呼吸驱动与更差的临床结果相关，而其他研究则证明了相反的结果。 我们还证明了使用肺泡气体测量仪进行气体交换的非侵入性评估 (AGM)可以预测谁将因COVID-19感染而需要补充氧气。其他研究 在COVID-19大流行之前的研究表明， 变化和死腔升高均与ARDS的不良结局相关。但许多 这些研究集中于已经插管和机械通气的患者。关于这一点，我们所知甚少。 这些参数在自主呼吸个体中的相关性。几年来， 患者自身造成的肺损伤（P-SILI）在医学文献中得到了越来越多的关注。基本概念是 由于现有肺损伤而即将发生呼吸衰竭的患者可能会导致其 肺如果患者自主呼吸，呼吸驱动过高， 过度的负吸气努力导致主要的经尿道压力变化。的结果 这些异常是大的潮气量，如机械通气的人与伤害潮气量 在低潮气量通气（LTVV）出现之前。此外，回顾性审查大型队列研究， 对ARDS患者的随机对照试验表明， 插管往往产生过大的潮气量。他们随后的肺损伤是否 完全由于其潜在的ARDS病理或部分由于叠加的P-SILI尚不清楚。如果 存在自发呼吸个体中即将发生呼吸衰竭的生理特征， 与升高的呼吸驱动相关，随后可以采取步骤来减轻增加的驱动， 研究这些变量在发生呼吸衰竭的患者中的纵向影响。此外，如果这样的 签名存在，干预消除了一些随后的肺损伤，这是一个强有力的证据， 体内P-SILI的概念。我们的目标是测试三个独立但相关的假设。首先，年度股东大会是一部小说 和简单的技术，可用于确定患者在呼吸衰竭的风险增加， 传统的度量。其次，屏气动作是一种有效的技术，以评估控制呼吸 可以识别出呼吸道预后不良的患者。第三，气道阻塞压力将提供 在识别高风险患者方面具有额外的预测价值。该提案将为PI奠定基础， 获得经验和培训，为长期和富有成效的学术医疗生涯。

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.