This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this proposal is to further understand the pathogenesis of acute respiratory failure in children with community-acquired pneumonia (CAP). The central hypothesis is that the continuum of CAP-induced lung injury, from minimal lung injury to severe respiratory failure and acute respiratory distress syndrome (ARDS), represents, in part, an imbalance between pro-inflammatory/pro-fibrotic/and anti-inflammatory/anti-fibrotic mediators, and that this imbalance is in part influenced by genetic determinants. This proposal will examine if specific genetic polymorphisms are associated with the clinical presentation of, or outcome from, CAP-induced lung injury and respiratory failure in children. The project will seek evidence of genetic markers called single nucleotide polymorphisms (SNPs) that can be utilized to predict children with CAP that are at high risk for poor outcomes and may benefit from earlier or more aggressive intervention. To test our hypothesis, the specific aim of this proposal is as follows: To test the prediction that known (SNPs) in genes involving inflammation, specifically IL-1beta and IL-1 receptor antagonist, are associated with CAP-induced severe lung injury and respiratory failure in children. This proposal will utilize a multi-disciplinary approach to analyze and compare frequencies of specific genetic polymorphisms in children with varying degrees of CAP-induced severe lung injury and respiratory failure. The research team will include investigators trained in Pediatric Critical Care at Le Bonheur Children's Medical Center and Pediatric Critical Care at Children's Memorial Hospita
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