Every year, more than 100,000 children in the United States require admission to a Pediatric Intensive Care Unit (PICU) with mechanical ventilation support. Of these, one in ten have significant acute lung injury referred to as Pediatric Acute Respiratory Distress Syndrome (PARDS). The majority of these children survive their arduous PICU course, but little is known about their long-term functional outcomes. Adult survivors of mechanical ventilation and ARDS are known to suffer from long-term significant impairments including decreased exercise tolerance, inability to return to work, and low health-related quality of life (HRQOL). There remains a significant knowledge gap in the understanding of long-term outcomes in children who survive prolonged mechanical ventilation and PARDS. In this proposal, we will employ two methods to evaluate the long-term physical functioning of children who survive mechanical ventilation and PARDS. First, we will link detailed data from the inpatient electronic health record to post-discharge outpatient insurance claims data to identify natural clusters of functional outcome phenotypes and the predictive patient and hospitalization characteristics in a large retrospective cohort of children admitted to our PICU who require > 3 days of mechanical ventilation (Aim 1). Second, we will establish a prospective cohort of critically-ill mechanically ventilated children to evaluate post-discharge HRQOL, functional status, and physical activity (Aim 2). We will use accelerometry, a novel, objective measure of physical activity to build upon the currently used, subjective measures of physical functioning. We hypothesize that we will be able to identfy and validate functional outcome phenotypes and predictors of phenotype clusters (Aim 1). Additionally, we hypothesize that severity of PARDS as well as a threshold of duration of mechanical ventilation, a metric of exposure to PICU-related therapies, will be associated with worse functional outcomes including impaired functional recovery and decreased physical activity (Aim 2). The results of this proposal will identify a cohort of critically ill children who are at high risk of poor functional recovery and most likely to benefit from targeted interventions to improve long-term outcomes. These studies will lay the groundwork for Dr. Maddux to obtain the necessary expertise in pediatric critical care outcomes research to employ accurate, clinically-meaningful long-term outcome measures to evaluate targeted in-hospital and post-discharge therapies in clinical trials with the goal to improve the long-term physical functioning of critically ill children. Addditionally, a well orchestrated career development plan will provide the necessary training for Dr. Maddux to become an independent investigator focused on long-term outcomes after critical illness with the skills to evaluate large databases and perform prospective cohort follow-up.
Children who survive Acute Respiratory Distress Syndrome and critical illness requiring prolonged mechanical ventilation likely suffer the significant and long-lasting impairments described in adults and these morbidities may be improved through targeted inpatient or post-discharge interventions. We will use a large retrospective cohort of critically ill children who survived an episode of prolonged mechanical ventilation to identify functional outcome phenotypes and predictors available from their index hospitalization and a similar prospectively enrolled cohort to perform an in-depth evaluation of post-discharge health-related quality of life, functional status, pulmonary function, and physical activity level. This proposal will inform future clinical trials in critically ill children by generating prognostically enriched cohorts and validated outcome measures to test targeted interventions to improve long-term outcomes in children who survive prolonged mechanical ventilation and acute respiratory distress syndrome.
