Prognostic modeling of pediatric tracheostomy-associated respiratory tract infections
NIH
JOHNS HOPKINS UNIVERSITY
PROJECT SUMMARY: Each year over 4,000 children undergo tracheotomy and account for more than 20,000 hospitalizations annually most commonly due to acute tracheostomy-associated respiratory infections (TARI). These hospitalizations are most often due to Pseudomonas aeruginosa infection. Efforts to improve the care of children with tracheostomy are challenged by the limited body of evidence on how patient factors, features of P. aeruginosa itself, and the child's immune response impact the risk of recurrent infection. This proposal will address this critical knowledge gap by identifying and characterizing prognostic factors for frequent rehospitalization in children hospitalized for TARI. In this K23 Mentored Career Development Award, Dr. John Morrison will: 1) leverage existing data from a six-center prospective cohort study of children hospitalized for TARI to identify clinical factors associated with recurrent TARI hospitalization; 2) prospectively determine the association of pathogen-specific factors and features of the host immune response with frequency of recurrent TARI hospitalization, and 3) derive a novel prognostic model incorporating clinical and molecular factors to identify patients at increased risk for recurrent TARI hospitalization. Achieving these aims will facilitate Dr. Morrison's long-term goal of leading prognostically-stratified interventional studies aimed at improving outcomes for children with tracheostomy and others affected by frequent respiratory infections. The applicant has dedicated his career to improving the care for children with chronic respiratory failure and other medical complexity as a physician-scientist. He is an Assistant Professor of Pediatrics with the Johns Hopkins University (JHU) School of Medicine at Johns Hopkins All Children's Hospital (JHACH) who seeks a mentored career development award during which he will develop the advanced training, education, and experience to become an independently funded investigator in biomarker-informed prognostic models and risk- stratified clinical trials in children with tracheostomy. This proposal will provide Dr. Morrison with the support needed to advance his career by 1) acquiring knowledge on the development and application of prognostic modeling, 2) developing expertise in conducting biospecimen-based translational research, 3) preparing to conduct a prospective, multicenter study validating a prognostic model and examining therapeutic strategies, and 4) expanding his practical understanding of individual- and system-level factors contributing to recurrent admissions among children with tracheostomy. Dr. Morrison will be supported by the extensive resources of the Institutes for Clinical and Translational Research at JHACH and JHU and has assembled a strong team of mentors with expertise in biomarker discovery, biomarker-informed prognostic modeling, and risk-stratified clinical trials. He will also pursue coursework through the JHU Bloomberg School of Public Health in biostatistics, molecular epidemiology, and clinical trial conduct to complement his experience in the basic and clinical sciences and acquire the skills necessary to transition to independence. PROJECT NARRATIVE: Little is known regarding why children with tracheostomy experience recurrent respiratory infections despite receiving clinically appropriate antibiotic therapy. This proposal seeks to derive a novel prognostic model that incorporates clinical factors and mechanistically-based laboratory measures of pathogen antibiotic resistance and host immune response to identify children at greatest risk for recurrent tracheostomy-associated respiratory infections (TARIs). The findings of this work under a career development award will provide the basis for future risk-stratified interventional trials employing targeted therapies to reduce the frequency of TARI hospitalization among children with tracheostomy.
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