Pneumonia is the leading killer of children worldwide, responsible for one in five pediatric deaths annually, including nearly 2 million deaths each year among children less than 5 years of age. In the United States (US), despite low overall mortality, pneumonia remains the most common indication for hospitalization among children, with a significant proportion of children experiencing severe disease requiring intensive cardiorespiratory interventions and prolonged hospitalization. Despite this enormous burden, substantial knowledge gaps exist regarding precise determinants of disease severity and expected outcomes for children with pneumonia. The result is wide variation in management-including site of care decisions, diagnostic testing, and use of antimicrobials-with downstream effects on individual outcomes and societal costs. Thus, improving our understanding of pneumonia disease severity, including the ability to accurately predict outcomes, is a critical area of unmet need. The research detailed in this proposal responds directly to this need and includes the following scientific aims: 1) Develop and rigorously validate a clinical prediction rue using proportional odds logistic regression that predicts risk for severe outcomes among children hospitalized with community-acquired pneumonia (CAP); 2) Incorporate the determination of microbiologic data into the model to assess the influence of pneumonia etiology on performance characteristics of the prediction rule; 3) Externally validate the clinical prediction rule among a prospective observational cohort of children presenting to the emergency department with CAP. For the past two and one half years, the candidate has worked closely with his mentor and other investigators to conduct prospective, population-based surveillance for CAP hospitalizations among children in three US cities to determine disease incidence and comprehensive microbiologic etiology. This study includes over 2500 children with CAP and will serve as the exclusive data source for the development and initial validation of the proposed prognostic studies (scientific aims 1 and 2).
Aim 3 will enroll 300 children in the emergency department requiring hospital admission for CAP in a prospective validation study to ensure accurate predictive performance of the developed models in new populations and assess their potential clinical applicability. The overarching objective of this mentored career development experience is for the candidate to emerge as an independent clinical investigator leading a multidisciplinary research program to improve care and outcomes for children with pneumonia. To accomplish this goal, the candidate will augment his prior research training with advanced coursework and practical skills development in predictive modeling, clinical research, implementation science, and leadership training. Throughout the award period, the candidate will work closely with a multidisciplinary team of mentors and advisors-including experts in infectious diseases, biostatistics, hospital medicine, and epidemiology-to carry out his stated career and scientific aims.

Public Health Relevance

This proposal seeks to better understand determinants of disease severity for children with pneumonia, the leading killer of children worldwide and the most common reason for childhood hospitalization in the United States. Knowledge of these factors and their often complex interactions will be used to predict risk for severe outcomes among children hospitalized with pneumonia, and could be applied in clinical settings to improve care and outcomes for this population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
6K23AI104779-05
Application #
9252817
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Lu, Kristina
Project Start
2013-02-01
Project End
2017-01-31
Budget Start
2016-05-01
Budget End
2017-01-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232
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Stockmann, Chris; Ampofo, Krow; Killpack, Jarrett et al. (2018) Procalcitonin Accurately Identifies Hospitalized Children With Low Risk of Bacterial Community-Acquired Pneumonia. J Pediatric Infect Dis Soc 7:46-53
Bozio, Catherine H; Flanders, W Dana; Finelli, Lyn et al. (2018) Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia. Open Forum Infect Dis 5:ofy061
Self, Wesley H; Balk, Robert A; Grijalva, Carlos G et al. (2017) Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clin Infect Dis 65:183-190
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Neuman, Mark I; Hall, Matthew; Lipsett, Susan C et al. (2017) Utility of Blood Culture Among Children Hospitalized With Community-Acquired Pneumonia. Pediatrics 140:
Harris, Aaron M; Bramley, Anna M; Jain, Seema et al. (2017) Influence of Antibiotics on the Detection of Bacteria by Culture-Based and Culture-Independent Diagnostic Tests in Patients Hospitalized With Community-Acquired Pneumonia. Open Forum Infect Dis 4:ofx014
Williams, Derek J; Edwards, Kathryn M; Self, Wesley H et al. (2017) Effectiveness of ?-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia. JAMA Pediatr 171:1184-1191
Schlaberg, Robert; Ampofo, Krow; Tardif, Keith D et al. (2017) Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia. J Infect Dis 216:688-696
Bramley, Anna M; Reed, Carrie; Finelli, Lyn et al. (2017) Relationship Between Body Mass Index and Outcomes Among Hospitalized Patients With Community-Acquired Pneumonia. J Infect Dis 215:1873-1882

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