Non-invasive oscillometry to measure lung mechanics, response to treatments, and predict longer-term pulmonary outcomes among preterm infants: a prospective cohort study

摘要 这项以患者为导向的导师研究职业发展奖(K23)的目的是提供 科尔姆·特拉弗斯，医学博士，拥有成为 独立的临床科学家和新生儿肺结局研究的领导者。他长期的职业生涯 目标是减轻36万早产幸存者日益增加的呼吸道疾病负担 每年在美国通过新的观察性和干预性研究和大规模多中心临床 减少肺损伤的干预措施的试验。为了实现这些目标，并过渡到独立。 特拉弗斯和他的导师制定了一项全面的研究和职业发展计划，其中包括 来自具有良好指导记录的杰出科学家团队的指导；密集的说教 培训，包括完成公共卫生成果研究理学硕士学位；以及一项研究 有目的地提供体验式学习的计划，高级研究方法研究 早产儿的肺部结局。早产幸存者喘息的风险增加， 儿童时期的哮喘和肺功能异常试验(PFT)。早产儿肺功能的研究 婴儿一直受到完成婴儿PFT的困难的限制，限制了测量能力 疾病严重程度，评估治疗反应，并了解发育肺健康轨迹。Dr。 特拉弗斯最近使用一种创新的非侵入性振荡法完成了两项前瞻性队列研究 对足月和早产儿自主呼吸的肺力学进行量化的技术。他的早期 研究发现，足月儿和早产儿之间的肺力学差异是可以重复的。 测量并持续到排出。在这份K23提案中概述的研究计划中，特拉弗斯博士将 在这部小说的基础上展开，他的具体研究目标与他的培训计划直接一致 以下是：(1)确定健康足月婴儿之间肺力学差异的程度 出生后有或没有肺部疾病的早产儿一直持续到出院或40周后 月经后年龄，(2)量化接受药物治疗的早产儿的肺力学变化 对于肺部疾病，以及(3)确定检测到肺力学异常的程度 出院前持续存在，并在24个月时预测较长期的肺部结果。一种非侵入性方法 在出院前测量肺力学并预测较长期的肺结果可以 从根本上改变我们对出生后早期肺发育对肺功能影响的理解 在早产儿身上。此外，一种非侵入性床边设备，可以客观地测量对 治疗将是一项重要的研究和临床工具。以所获得的技能和洞察力为基础 通过拟议的培训和研究计划，特拉弗斯博士将申请R01以确定效果 儿童早期对肺力学和肺健康的早期干预和治疗。

SUMMARY The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Colm Travers, MD, with the mentorship, training, and research experience needed to become an independent clinician scientist and leader in neonatal pulmonary outcomes research. His long-term career goal is to reduce the increasing burden of respiratory morbidity among the 360,000 survivors of preterm birth per year in the US through novel observational and interventional studies and large scale multi-center clinical trials of interventions that reduce lung injury. To achieve these goals and transition to independence, Dr. Travers and his mentors developed a comprehensive research and career development plan that includes mentorship from an exceptional team of scientists with proven track records of mentorship; intensive didactic training including completion of a Master of Science in Public Health in Outcomes Research; and a research plan that is purposefully designed to provide experiential learning in advanced research methods to study pulmonary outcomes among preterm infants. Survivors of preterm birth are at increased risk for wheeze, asthma, and abnormal pulmonary function tests (PFTs) during childhood. Studies of lung function in preterm infants have been limited by the difficulties with completing infant PFTs, restricting the ability to measure illness severity, assess response to treatments, and understand developmental lung health trajectories. Dr. Travers recently completed two prospective cohort studies using an innovative non-invasive oscillometry technique to quantify pulmonary mechanics in spontaneously breathing term and preterm infants. His early work observed that differences in lung mechanics between term and preterm infants can be reproducibly measured and persist until discharge. In the research plan outlined in this K23 proposal, Dr. Travers will expand upon this novel work, and his specific research aims are directly aligned with his training plan as follows: (1) To determine the extent to which differences in lung mechanics between healthy term infants and preterm infants with and without lung disease after birth persist until discharge from hospital or 40 weeks’ postmenstrual age, (2) To quantify changes in lung mechanics among preterm infants receiving medications for lung disease, and (3) To determine the extent to which abnormalities in pulmonary mechanics detected before discharge persist and predict longer-term pulmonary outcomes at 24 months. A non-invasive method to measure lung mechanics and predict longer-term pulmonary outcomes before discharge from hospital can fundamentally change our understanding of the effect of early postnatal lung development on lung function in preterm infants. In addition, a non-invasive bedside device that objectively measures response to treatments would be both a vital research and clinical tool. Building upon the skills and insights acquired through the proposed training and research plan, Dr. Travers will apply for an R01 to determine the effects of early interventions and therapies on lung mechanics and pulmonary health in early childhood.