Transforming Exercise Testing and Physical Activity Assessment in Children: New Approaches to Advance Clinical Translational Research in Child Health

儿童是体力活动最活跃的人类；体力活动减少是儿童健康的主要标志 儿童疾病和运动测试提供了对健康和疾病的机械性见解，这些通常是 在孩子休息时隐藏起来。尽管如此，因为数据分析和测试协议未能 与使能技术和计算能力保持同步，健身和体力活动的生物标记物 尚未广泛纳入儿童健康的转化性研究和临床实践。这样做的目的是 该项目旨在解决阻碍心肺运动试验(CPET)最佳使用的障碍 在孩子们身上。目标1是重新思考和改变目前儿童典型CPET的临床研究应用 通过新的逐个呼吸技术和数据分析方法的实施。目标2是发展 新的运动测试方案(多个简短的运动回合)，更接近现实生活中的模式 体力活动，并在这样做时，更好地评估相关的病理生理学。目标3是识别和克服 后勤问题限制了涉及运动生物标记物的多中心研究。我们的用例，镰状细胞 疾病和囊性纤维化，突出了不同的疾病如何会损害运动和体力活动。这个 将通过各种方式分析新的CPET方法的价值，包括：1)建立指数 健康(例如，身体成分)；2)习惯性体力活动，这是衡量整体健康的新兴指标；3) 循环血液中新的运动反应基因表达信号。与健康相结合 作为比较，我们的项目将描述CPET生物标记物在广泛的 儿科健康和疾病。我们将利用赠款周期并前瞻性地研究队列，因为我们的 参与者的成长和成熟从2-3岁到5岁，大约间隔3年。这提供了独一无二的 有机会在关键的成长时期纵向研究CPET对健康和疾病的影响。我们的团队 代表了多样化和具有挑战性的学术健康中心和附属的独立儿童 经常参与多中心儿科转化研究的医院：1)加州大学欧文分校 2)西北大学临床与翻译科学研究所 3)洛杉矶儿童医院南加州临床和翻译科学研究所 南加州大学洛杉矶分校。这些中心中的每个都致力于服务不足的人群。在……里面 此外，我们将与北美儿科运动医学会和美国 运动医学学院，每个致力于促进运动即医学的儿童。通过我们的 建议：1)常用CPET数据分析的创新，2)开发新的测试范式，3) 向研究界提供基本数据，以确定统计能力和分析方法 针对运动生物标记物，以及4)改善多中心试验的互操作性，该项目将刺激 将运动生物标记物用作关键结果变量的儿童健康临床研究。

Children are the most naturally physically active human beings; reduced physical activity is a cardinal sign of childhood disease, and exercise testing provides mechanistic insights into health and disease that are often hidden when the child is at rest. Despite this, and because data analytics and testing protocols have failed to keep pace with enabling technologies and computing capacity, biomarkers of fitness and physical activity have yet to be widely incorporated into translational research and clinical practice in child health. The goal of this project is to address the obstacles that have impeded optimal use of cardiopulmonary exercise testing (CPET) in children. Aim 1 is to rethink and transform current clinical research applications of typical CPET in children by novel implementation of breath-by-breath technologies and data analytic approaches. Aim 2 is to develop new exercise testing protocols (multiple brief exercise bouts) that more closely mimic real-life patterns of physical activity and, in so doing, better assess relevant pathophysiology. Aim 3 is to identify and overcome logistical issues that have limited multicenter studies involving exercise biomarkers. Our use-cases, sickle cell disease and cystic fibrosis, highlight how very different diseases can impair exercise and physical activity. The value of the new CPET approaches will be analyzed in a variety of ways, including by: 1) established indexes of health (e.g., body composition), 2) habitual physical activity, an emerging metric of overall health, and 3) novel exercise-responsive gene expression signals in the circulating blood. In combination with healthy children as comparisons, our project will delineate the use of CPET biomarkers across a broad spectrum of pediatric health and disease. We will take advantage of the grant cycle and study cohorts prospectively as our participants grow and mature from Tanner 2–3 to 5, roughly a 3-year interval. This provides the unique opportunity to study CPET longitudinally in health and disease over a critical period of growth. Our team represents the diverse and challenging array of academic health centers and affiliated stand-alone children’s hospitals often involved in multicenter pediatric translational research: 1) University of California at Irvine Institute for Clinical and Translational Science, 2) Northwestern University Clinical and Translational Sciences Institute, and 3) the Southern California Clinical and Translational Science Institute, Children’s Hospital of Los Angeles, University of Southern California. Each of these centers is committed to underserved populations. In addition, we will collaborate with the North American Society of Pediatric Exercise Medicine and the American College of Sports Medicine, each dedicated to advancing exercise-as-medicine in children. Through our proposed: 1) innovations in data analytics of commonly used CPET, 2) developing new testing paradigms, 3) providing the research community with essential data to determine statistical power and analytic approaches specific for exercise biomarkers, and 4) improving interoperability in multicenter trials, the project will stimulate child health clinical research in which exercise biomarkers are used as key outcome variables.