Early Respiratory Care in Amyotrophic Lateral Sclerosis Patients at High Risk for Respiratory Failure

项目摘要/摘要 呼吸衰竭通常发生在肌萎缩侧索硬化症(ALS)中，并导致显著的发病率 和死亡率。开始出现呼吸无力预示着与球相关的吸入风险增加。 肌肉无力和无效咳嗽，慢性低通气引起的高碳酸血症呼吸衰竭，以及 肺部感染，最终导致死亡。尽管呼吸衰竭在发病率和死亡率中起着关键作用 与肌萎缩侧索硬化症相关的死亡率，仍然存在关于最佳启动和维持的不确定性 这种疾病的呼吸系统护理。肌萎缩侧索硬化症的临床表现和症状非常不同。 进展，这会导致呼吸损害的不同演变。鉴于呼吸系统的重要性 这种疾病的发病率与不清楚的时间相结合，识别高危亚组可能有助于 研究早期呼吸干预的结果。我们小组发布了一种临床预测工具， 可以预测ALS患者在六个月内发生呼吸衰竭的高风险。我们还出版了一个潜在的班级 肌萎缩侧索硬化症患者不同用力肺活量轨迹亚型分析 时间到了。将我们的临床预测工具和表型知识应用于ALS患者样本 确定一个适合未来临床试验的亚组。然而，考虑到ALS的情感负担，患者 对呼吸干预措施的看法对成功实施至关重要。据我们所知，一个 对呼吸衰竭高风险的ALS患者队列的前瞻性研究尚未进行。 这项研究的目标是使用我们的临床预测工具来确定新诊断的ALS的患病率 高危呼吸衰竭患者，阐明患者对早期呼吸护理的看法，并 在高危患者中开展肺容量募集试点。这项提议将涉及一个多中心 在费城的三个学术中心学习。我们将对患有以下疾病的患者进行前瞻性队列研究 ALS，应用我们的临床预测工具，并在一年多的时间里监测他们的呼吸衰竭。我们将使用半- 有组织的访谈，收集患者关于他们在什么情况下会接受的观点 肌萎缩侧索硬化症的早期呼吸护理。第三，实施单臂肺容量募集试点干预 在新诊断的ALS患者中，呼吸衰竭的高危患者在六个月内。 该项目将为研究项目拨款申请提供必要的初步数据，该申请将(1)进行 高危ALS患者早期呼吸治疗的随机对照试验(2)阐明医生和 护理人员对ALS患者呼吸护理的看法，以及(3)确定哪些特征与 具有不同的呼吸功能轨迹，从而允许个性化用药。

Project Summary/Abstract Respiratory failure commonly occurs in amyotrophic lateral sclerosis (ALS) and leads to significant morbidity and mortality. The onset of respiratory weakness heralds an increased risk of aspiration related to bulbar muscle weakness and ineffective cough, hypercapnic respiratory failure due to chronic hypoventilation, and pulmonary infections, ultimately leading to death. Despite the key role of respiratory failure in the morbidity and mortality associated with ALS, there remains uncertainty concerning optimum initiation and maintenance of respiratory care for this disease. ALS has a very heterogeneous clinical presentation and symptom progression, which causes variable evolution of respiratory involvement. Given the significance of respiratory morbidity with this disease combined with the unclear timing, identifying high-risk subgroups may facilitate studying outcomes of early respiratory interventions. Our group has published a clinical prediction tool which can predict a high risk of respiratory failure within six months in ALS. We have also published a latent class analysis to identify subphenotypes of ALS patients by their differing trajectories of forced vital capacity over time. Applying our clinical prediction tool and knowledge of phenotypes to a sample of ALS patients would identify a subgroup suitable for future clinical trials. However, given the emotional burden of ALS, patient perspectives on respiratory interventions are critical to successful implementation. To our knowledge, a prospective investigation on a cohort of ALS patients at high risk of respiratory failure has yet to be performed. The goals of this study are to use our clinical prediction tool to identify the prevalence of newly-diagnosed ALS patients at high risk of respiratory failure, to elucidate patient perspectives on early respiratory care, and to implement a pilot trial of lung volume recruitment in high-risk patients. This proposal will involve a multicenter study at three academic centers in Philadelphia. We will perform a prospective cohort study of patients with ALS, apply our clinical prediction tool, and monitor them for respiratory failure over one year. We will use semi- structured interviews to gather patient perspectives regarding circumstances under which they would accept early respiratory care in ALS. Third, we will perform a single-arm pilot intervention of lung volume recruitment in newly-diagnosed ALS patients at high risk of respiratory failure within six months. This project will provide essential preliminary data for a Research Project Grant application that will (1) conduct a randomized controlled trial of early respiratory therapy in high-risk ALS patients (2) elucidate physician and caregiver perspectives regarding respiratory care in ALS, and (3) identify which characteristics are associated with different trajectories of respiratory function, thus allowing for personalized medicine.