New, generalizable approaches are needed for measuring physical fitness and activity across a spectrum of pediatric health and disease.

Exercise in children and adolescents is not merely play but is an essential component of growth and development. Children are among the most spontaneously physically active human beings. It is not surprising that participation in PA (Physical Activity) is a major determinant of health across the lifespan and health-related quality of life in both healthy children and in children with chronic diseases. Despite this essential biologic role for PA, children have not been spared the relentless reduction in levels of PA that is creating a crisis in health care in our nation and throughout the world. Recognition of the enormous morbidity and cost of physical inactivity-related diseases, such as atherosclerosis, type 2 diabetes, and osteoporosis, has spurred new policy initiatives targeting preventive medicine early in life. The concept of pediatric origins of adult health and disease is gaining scientific merit, highlighting the need to transform existing notions of how to evaluate health in a growing child. A physically inactive (even normal weight) child may have no symptoms of disease, but evidence of deterioration in vascular health may already be present. As era of population health management and precision medicine are approaching, the notion of what it means to be a healthy child must change and include robust metrics of physical fitness.

Equally worrisome is that the deleterious health effects of physical inactivity and poor fitness are exacerbated in children with chronic disease and/or disabilities or with environmental-lifestyle conditions like obesity. Children with diseases or conditions previously associated with mortality during the first two decades of life (e.g., SCD, CF) are living longer due to remarkable advances in research and care, but are often unable to achieve levels of PA and fitness associated with health benefits in otherwise healthy children. Not surprisingly, the healthspan \[the period of life free from serious chronic diseases and disability of children with chronic diseases is threatened not only by the underlying disease, but by the compounding effects of insufficient PA and sedentary behavior. Increasing PA and fitness is feasible, but has proven quite challenging to implement in a systematic manner. Once a pattern of physical inactivity and a sedentary lifestyle is established, a vicious cycle ensues, in which constraints on PA harm immediate health and contribute to lifelong health impairment ranging from cardiovascular and metabolic disease to osteoporosis. Exactly what constitutes ideal physical fitness in a child with a chronic condition remains unknown. Finding beneficial levels of PA in children with chronic disease or disability is challenging because the optimal range of exercise is much narrower than in a healthy child. Finally, as a result of the COVID-19 pandemic a sizable number of children are experiencing long-term effects such as fatigue, and will be included in our study. Similar to children with CF and SCD, studies of exercise and physical activity will provide insight into disease mechanisms and possible therapies.