Prosper: pulmonary recovery and outcomes after severe pediatric respiratory illness

The National Heart, Lung, and Blood Institute awarded Seattle Children's Hospital $930,637 under the Cardiovascular Diseases Research program (CFDA 93.837) on September 1, 2026, to conduct PROSPER (Pulmonary Recovery and Outcomes After Severe Pediatric Respiratory Illness), a multicenter prospective longitudinal cohort study examining how impaired pulmonary function contributes to physical and health-related quality-of-life morbidity among children surviving acute respiratory failure.

The study will enroll children treated with invasive or non-invasive mechanical ventilation for acute parenchymal or lower airway disease and assess pulmonary function, physical activity, sleep, resting heart and respiratory rate, and patient- and caregiver-reported outcomes serially over one year following hospital discharge. The research addresses a gap in understanding lung function recovery trajectories following acute respiratory illness in pediatric populations, where small prior studies were limited by high attrition, single-timepoint assessment, and applicability only to children six years and older without cognitive impairment. The objectives include describing recovery trajectories of pulmonary function, identifying risk factors for poor long-term outcomes, and determining targets for interventions to improve outcomes in this growing population.

The award funds work performed at Seattle Children's Hospital in Seattle, Washington, with a period of performance from September 1, 2026, through May 31, 2031. The assistance type is a Project Grant.

Abstract

Acute respiratory failure, typically resulting from conditions such as severe pneumonia, bronchiolitis, or asthma, is the most common cause of critical illness among U.S. Children. Children surviving acute respiratory failure experience morbidities across a range of heath domains including physical function, health-related quality of life, and social reintegration. IT is not well understood, however, how lung function recovers following acute respiratory illness, or the degree to which impaired pulmonary function impacts a child's physical activity, quality of life, or participation in school and activities. Small studies have demonstrated high but variable prevalence of impaired pulmonary function among children surviving severe hypoxemic respiratory failure, but most only assessed patients at a single timepoint and were limited by high study attrition due to the burden of returning for in-person testing. Additionally, these studies only evaluated participants using spirometry, which can only be performed by children ages 6 years and older without cognitive impairment. The objectives of this study are to understand how impaired pulmonary function contributes to physical and health-related quality of life morbidity among children surviving acute respiratory failure and to identify risk factors for poor outcomes in order to identify targets for interventions to improve long-term outcomes in this growing population. We will conduct a multicenter, prospective, longitudinal cohort study of children treated with invasive or non-invasive mechanical ventilation for acute parenchymal or lower airway disease and assess pulmonary function, physical activity, sleep, resting heart and respiratory rate, and patient- and caregiver-reported outcomes serially over one year following hospital discharge. Specifically, we aim to 1) describe the trajectory of recovery of pulmonary function over the year following pediatric ARF and quantify the severity of pulmonary function impairment relative to that of a matched disease control cohort without recent acute respiratory illness; 2) evaluate associations between the trajectory of recovery of pulmonary function and the trajectories of recovery of physical activity, physiologic measures, respiratory symptoms, hrql, and participation in school and activities; and 3) identify patient and clinical risk factors for impaired pulmonary function recovery. We will use novel technologies to expand cohort representation and retention, assessing pulmonary function using remote spirometry for children 6 years and older and portable oscillometry for younger children and those with cognitive impairment, who represent the majority of pediatric intensive care unit patients with respiratory failure. These innovations will facilitate the largest-scale evaluation to date of pulmonary function following pediatric acute respiratory failure and will for the first time assess the intersection of pulmonary function with physical activity and patient-reported outcomes. Identification of children at highest risk for impaired recovery of pulmonary function and related morbidities will facilitate development of targeted interventions aimed at pulmonary and physical recovery following pediatric acute respiratory failure.