Minimally invasive techniques to measure upper airway obstruction in children

描述（由申请人提供）：这是一个令人难以置信的特权，以照顾儿童在他们最关键的时刻。作为儿科重症监护医生，我们必须能够为这些儿童提供及时和有证据的护理，并支持家庭了解自己选择的治疗方法是基于证据和经验的。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，我有责任为我的病人提供最高的，基于证据的护理，并通过进行研究来收集最佳实践的证据，帮助我们的专业发展。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个彻底和严格的临床研究人员。虽然我在统计学和临床调查方面有本科和研究生水平的经验，但由于儿科疾病的“罕见性”，需要多中心研究来得出有关危重儿童的有意义的结论。这对于机械通气的儿童尤其重要，因为这是儿科重症监护中最常见但最多变的干预措施。为了进行多中心机械通气试验，我必须掌握有关设计和实施此类试验的知识和技能，并获得评估通气儿童试验潜在客观结果的专业知识。本申请中详细介绍的具体研究项目是培养这些技能的第一步。利用动物模型验证上气道阻塞的微创测量，并随后将该测量应用于单个部位的机械通气儿童，我希望掌握与肺功能评估相关的技能， 特别是上呼吸道阻塞。上呼吸道阻塞是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。这是一个更大的问题，在儿童（与成人相比），因为它是估计在临床上的理由，1/3的所有小儿拔管失败的原因是上呼吸道阻塞。然而，拔管后气道阻塞的危险因素和针对拔管后气道阻塞的治疗是不一致的，可能是因为缺乏测量上气道阻塞的临床敏锐性。因此，该项目描述了验证一种微创技术来测量上呼吸道阻塞，最初在恒河猴。然后将其应用于儿童，以评估临床喘鸣量表的准确性，并通过证明客观、非侵入性措施的改善来确定常用治疗或支持性护理是否影响气道阻塞的解决。虽然这项研究将使我具备进行临床试验的重要技能，但我将通过与NICHD协作儿科重症监护研究网络（CPCCRN）和儿科急性肺损伤和脓毒症研究者（PALISI）网络的一系列会议和活动，获得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中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变为现实。

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.