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

儿童是最自然的体力活动的人;减少体力活动是一个主要的迹象， 儿童疾病，运动测试提供了对健康和疾病的机械见解， 当孩子休息的时候藏起来尽管如此，由于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，健康和身体活动的生物标志物 尚未被广泛纳入儿童健康的转化研究和临床实践。这个目标 该项目旨在解决阻碍心肺运动试验（CPET）最佳使用的障碍 小儿目的1是重新思考和改变目前典型的CPET在儿童中的临床研究应用 通过新颖的逐呼吸技术和数据分析方法的实现。目标二：发展 新的运动测试协议（多次短暂的运动回合），更接近地模仿现实生活中的模式， 身体活动，并在这样做，更好地评估相关的病理生理学。目标3：识别和克服 后勤问题限制了涉及运动生物标志物的多中心研究。我们的用例，镰状细胞 疾病和囊性纤维化，突出了非常不同的疾病如何损害锻炼和身体活动。的 新的CPET方法的价值将通过多种方式进行分析，包括：1）建立指数 健康（例如，身体组成），2）习惯性身体活动，整体健康的新兴指标，以及3） 循环血液中新的运动反应基因表达信号。结合健康 作为比较，我们的项目将在广泛的范围内描述CPET生物标志物的使用， 儿科健康和疾病。我们将利用赠款周期和研究队列前瞻性作为我们的 参与者从坦纳2-3岁成长到5岁，大约3年的时间间隔。这提供了独特的 有机会在成长的关键时期纵向研究CPET的健康和疾病。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独立儿童的阵列 经常参与多中心儿科转化研究的医院：1）位于欧文的加州大学 西北大学临床与转化科学研究所（2） 南加州临床和转化科学研究所，洛杉矶儿童医院 洛杉矶，南加州大学。每个中心都致力于服务不足的人群。在 此外，我们还将与北美儿科运动医学协会和美国 运动医学学院，每个致力于推进运动作为医学的儿童。通过我们 建议：1）常用CPET数据分析的创新，2）开发新的测试范式，3） 为研究界提供基本数据，以确定统计功效和分析方法 具体的运动生物标志物，和4）提高多中心试验的互操作性，该项目将刺激 儿童健康临床研究，其中运动生物标志物被用作关键结果变量。

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.