Minimally invasive techniques to measure upper airway obstruction in children

描述(由申请人提供)：在孩子们最关键的时刻照顾他们，这是一种难以置信的特权。作为儿科重症监护从业者，我们必须能够为这些儿童提供及时和有证据的护理，并支持家庭，使他们知道自己选择的治疗是基于证据和经验。然而，作为一个专业，我们只能通过严格的临床研究来创建基于证据的标准。致力于重症监护医学的职业生涯，为我的患者提供最高水平的循证护理，并通过开展研究为最佳实践收集证据，帮助我们的专业发展是我的责任。要做到这一点，我必须学习必要的技能，以促进我的发展成为一名彻底和严谨的临床研究人员。虽然我在统计学和临床调查方面有本科生和研究生水平的经验，但由于儿科疾病的“罕见”，需要多点研究来得出关于危重儿童的有意义的结论。这对机械通气的儿童尤其重要--这是儿科重症监护中最常见但最可变的干预措施。为了寻求进行多中心机械通风试验，我必须让自己掌握设计和实施此类试验的知识和技能，并获得评估有关呼吸机儿童试验的潜在客观结果的专业知识。申请表中详细说明的具体研究项目是我发展这些技能的第一步。使用动物模型验证上呼吸道阻塞的微创测量，然后将该测量应用于在单个位置进行机械通气的儿童，我希望掌握与肺功能评估相关的技能， 尤其是上呼吸道阻塞。上呼吸道阻塞是机械通气试验中的一个复杂因素，因为它延长了机械通气的时间。这在儿童中是一个更大的问题(与成人相比)，因为根据临床理由估计，所有儿童拔管失败的三分之一是由于上呼吸道阻塞造成的。然而，拔管后呼吸道阻塞的危险因素和治疗方法是不一致的，可能是因为缺乏测量上呼吸道阻塞的临床敏锐性。因此，这个项目描述了验证一种微创技术来测量上呼吸道阻塞，最初是在恒河猴身上。然后将其应用于儿童，以评估临床喘息评分的准确性，并通过展示客观、非侵入性措施的改善，确定常用的治疗方法或支持性护理是否影响呼吸道阻塞的解决。虽然这项研究将使我掌握进行临床试验的重要技能，但我将通过与NICHD儿科重症监护协作性研究网络(CPCCRN)和儿科急性肺损伤和脓毒症调查员网络(PALISI)的一系列会议和活动，获得关于多机构试验细微差别的具体经验。这些网络已经在危重儿童身上进行了许多多中心试验，并将帮助我学习必要的技能，将多中心试验从想法转化为现实。

DESCRIPTION (provided by applicant): It is an incredible privilege to take care of children at their most critical juncture. As pediatric critical care practitioners we must be able to provide timely and evidenced based care for these children, and support families with the knowledge that one's chosen treatment is based upon evidence and experience. However, as a specialty we can only create evidence based standards through rigorous clinical research. Committed to a career in intensive care medicine, it is my duty to provide my patients with the highest, evidence based care, and help our specialty grow by conducting studies to gather evidence for the best practices. To do this, I must learn the necessary skills to foster my development into a thorough and rigorous clinical researcher. While I have undergraduate and graduate level experience in statistics and clinical investigation, with the "rarity" of pediatric disease, multi-ite studies are needed to draw meaningful conclusions about critically ill children. This is particularly important for mechanically ventilated children-the most common yet most variable intervention in pediatric critical care. Seeking to conduct multi-center mechanical ventilation trials, I must equip myself with knowledge and skills about the design and implementation of such trials, and also gain expertise on evaluating potential objective outcomes for trials on ventilated children. The specific research project detailed in this application is the first step fr me to develop these skills. Using an animal model to validate a minimally invasive measure of upper airway obstruction and subsequently applying this measure to mechanically ventilated children at a single site, I hope to master skills related to the evaluation of pulmonary function, particularly upper airway obstruction. Upper airway obstruction is a complicating factor in ventilation trials because it prolongs length of mechanical ventilation. It is a bigger problem in children (compared to adults) as it is estimated on clinical grounds that 1/3 of all pediatric extubation failures result from upper airway obstruction. However, risk factors for and therapies targeting post-extubation airway obstruction are inconsistent, likely because clinical acumen to measure upper airway obstruction is lacking. Therefore, this project describes validating a minimally invasive technique to measure upper airway obstruction, initially in Rhesus Monkeys. It will then be applied in children to evaluate the accuracy of clinical stridor scales, and determine whether commonly applied therapeutics or supportive care impact resolution of airway obstruction, by demonstrating improvement in the objective, non-invasive measures. While this study will equip me with important skills to conduct clinical trials, I will get specifi experience with the nuances of multi-institutional trials through a series of meetings and activities with the NICHD Collaborative Pediatric Critical Care Research Network (CPCCRN) and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. These networks have undertaken many multi-center trials in critically ill children, and will help me learn the necessary skills to take a multi-center trial from an idea to reality.