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的不等。 需要有创性机械通气(即急性呼吸窘迫综合征或ARDS)。早些时候 呼吸衰竭患者常有气体交换、呼吸控制和/或肺功能异常。 机械师。在正在进行的新冠肺炎大流行期间，一些研究表明， 呼吸驱动与较差的临床结果有关，而其他研究结果则相反。 我们还证明了使用肺泡气体计对气体交换进行非侵入性评估 (AGM)是对谁需要新冠肺炎感染的补充氧气的预测。其他研究 在新冠肺炎大流行之前显示吸气努力增加，大的跨肺压 改变、增加死腔均与ARDS的预后较差有关。然而，许多人 这些研究的重点是已经插管和机械通气的患者。人们对此知之甚少 这些参数在自主呼吸个体中的相关性。几年来，人们一直认为 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 因现有肺损伤而即将发生呼吸衰竭的患者可能会对其 肺部。如果患者自发呼吸，呼吸动力过高，那么他们可能会产生 过度负的吸气努力导致较大的经肺压力变化。结果是 这些异常是巨大的潮气量，就像机械通风一样，会损害潮气量。 在低潮气量呼吸机(LTVV)出现之前。此外，对大型队列研究和 对ARDS患者的随机对照试验表明，自主呼吸患者在 插管往往会产生过大的潮气量。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P-Sili尚不清楚。如果一个 自主呼吸个体即将发生呼吸衰竭的生理特征是存在的 与升高的呼吸驱动相关联，随后可以采取步骤来减轻增加的驱动和 研究这些变量对发生呼吸衰竭患者的纵向影响。而且，如果这样的一个 签名的存在和干预消除了一些后续的肺损伤，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，可以用来更好地识别呼吸衰竭风险增加的患者 传统指标。其次，屏气动作是评估呼吸控制的有效技术 可以识别呼吸预后较差的患者。第三，气道闭塞压力将提供 在识别高危患者方面具有额外的预测价值。这项提议将为国际和平研究所奠定基础 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.