Recent discoveries across a broad range of basic science, technology and translational research have enhanced our understanding of disease processes and resulted in a multitude of potentially effective treatments for critically ill and injured children that require evaluation in the clinical environment. There is a tremendous need for a collaborative research network in pediatric critical care to facilitate the swift and effectie translation of scientific and technologic discoveries into clinical advances as well as to facilitae the flow of ideas from the bedside back to the laboratory. Access to appropriate patients and expertise in the execution of clinical trials must be linked to scientists and laboratories working within and across disciplines at the cutting edge of scientific advancement. At the University of Colorado Denver (UCD) and Children's Hospital Colorado (CHCO), we have a long history of successful collaborative basic and translational science programs, focused on integrated studies of cardiovascular-pulmonary responses to injurious stimuli at the molecular, cellular, organ, whole animal, and human subject levels. We will provide several unique areas of strength to the CPCCRN, including: 1) a distinctive translational approach to cardiovascular-pulmonary diseases, 2) experience with pediatric clinical trials execution, including innovative programs to enhance research awareness and participation among patients and families, 3) an eight state catchment area with high volumes of critically ill and injured children, 4) an in-house rehabilitation program and extensive outpatient outreach program in all pediatric specialties capable of providing follow-up care to nearly all our critically ill patients, and 5) a dynamic partnership with the Colorado Clinical Translational Science Institute to provide extensive research resources. Utilizing these assets, we will augment the contributions of CPCCRN to the care of critically ill children through innovative translational and clinical trial proposals, participation in Network leadership committees, and training the next generation of pediatric critical care researchers. Our concept proposal demonstrates our capacity to design innovative and relevant studies utilizing cutting edge methodologies. Ventilator associated pneumonia (VAP) is a serious complication of mechanical ventilation in critically ill children, yet there is limited understanding of the microbial and host factors associated with VAP. Endogenous bacteria are likely critical regulators of both pathogen behavior and host responses in the airways, modulating the virulence of potential pathogens. Limited understanding of the microbial and host factors associated with VAP has precluded development of truly effective prevention and treatment strategies. This study will assess how viral infection, bacterial populations, and the balance between host immune activation and immune suppression interact to determine whether a given patient develops VAP. Understanding how these critical interactions are involved in the pathogenesis of VAP will improve public health by identifying targets for more effective prevention and treatment strategies that will decrease the burden of VAP. 1
This proposal for the University of Colorado/Children's Hospital Colorado Pediatric Critical Care Program to join the CPCCRN research network describes our institution's commitment to pediatric critical care research and the extensive capabilities and experience which we would add to the network. We include a concept proposal for a study of the airway microbiome in critically ill children to determine how viral infection, bacterial populations, and the balance between host immune activation and immune suppression interact to determine whether a given patient develops ventilator associated pneumonia (VAP), and identify targets for more effective prevention and treatment strategies that will decrease the burden of VAP.