Urinary Proadrenomedullin to Improve Risk Stratification of Children with Community-Acquired Pneumonia

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PROJECT SUMMARY/ABSTRACT Although community-acquired pneumonia (CAP) is one of the most common serious bacterial infections in children, no validated decision tools exist to gauge illness severity among children with CAP. Without objective tools, management decisions are inefficient and potentially inaccurate, resulting in the use of unnecessary tests, therapies and hospitalizations in low-risk children or delays in critically important therapies in those at high risk of severe outcomes. The long-term goal of this research is to improve risk stratification of children with lower respiratory tract infections. Proadrenomedullin (proADM) is a vasodilatory peptide that, when measured in blood, has shown great potential to improve severity prediction in adults and children with CAP. Obtaining blood for biomarker measurements in children has several disadvantages, including pain, anxiety, invasiveness, and need for technical and procedural expertise. Proadrenomedullin can also be measured in urine, offering several important advantages, including ease of collection, cost effectiveness, and lack of discomfort. There is a paucity of data, however, on the role of urinary proADM in predicting clinical outcomes in children with suspected CAP. The overall objective of this R03 is to perform a proof-of-principle study to examine the ability of urinary proADM to predict clinical outcomes and disease severity in pediatric CAP. The scientific premise of the proposed study is based on (a) strong preliminary data from the PI's K23 that plasma proADM is associated with severe outcomes in suspected CAP in children, (b) feasibility testing finding a normally distributed range of concentrations of proADM in urine, (c) data demonstrating that plasma and urinary proADM levels are correlated, and (d) a body of literature suggesting that proADM is strongly associated with severe outcomes in adults with CAP. The specific aim of this R03 is to evaluate the association between urinary proADM levels and clinical outcomes in children with suspected CAP. The central hypothesis is that higher levels of urinary proADM will be associated with severe clinical outcomes. The investigators will leverage existing clinical data and urine specimens collected from 407 children at the time of initial evaluation as part of the PI's K23, a prospective cohort study of children 3 months to 18 years of age with suspected CAP who presented to the emergency department (ED). The proposed research is innovative in that it represents a new and substantive departure from the status quo by shifting the paradigm from inaccurate, subjective, or invasive risk stratification methods to an objective, accurate, rapid, and non-invasive approach that can be applied across multiple settings. This contribution is significant because effectively predicting disease severity in children with suspected CAP using proADM will ultimately improve the accuracy and reliability of management decisions by stratifying children into a high-risk group in need of focused and intensive therapies and a low-risk group for whom such therapies and resource use is unnecessary, ineffective, and potentially harmful.