Individualizing Steroid Use in Pneumonia

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PROJECT SUMMARY/ABSTRACT Pneumonia is the leading infectious cause of death worldwide. While inflammation is a hallmark pathologic feature of pneumonia, the use of corticosteroids to blunt the profound inflammatory response remains undefined. Decades of studies in heterogeneous populations failed to show a consistent benefit, leading to conflicting guidelines on the use of corticosteroids. Although corticosteroids have been shown to be effective in COVID-19 pneumonia, the use of corticosteroids in other infectious pneumonia remains unclear with high variability in clinical practice. This variability in practice presents an opportunity to see how corticosteroid administration in pneumonia can be optimized and tailored to patient specific characteristics. The objective of this study is to adapt advanced statistical and machine learning methods to already available robust observational data from the electronic health record to identify predictors of clinical deterioration and to develop an individualized treatment rule for steroid use in patients with community acquired pneumonia. This will be accomplished through three specific aims: 1) To develop and validate a machine learning prediction tool for in-hospital disease progression, 2) To develop and test an individualized treatment rule (ITR) for steroid use, and 3) To conduct a single center feasibility clinical trial comparing ITR and biomarker guided corticosteroid use and dosing to usual care in patients with community acquired pneumonia. We hypothesize that: 1) a combination of demographics, physiological parameters, clinical and laboratory data will be accurate in predicting risk of in-hospital disease progression and identifying steroid-responsive patients in whom benefit from adjunct corticosteroid treatment outweighs potential harm, and 2) ITR and biomarker-guided corticosteroid use, and dosing will be feasible. This career development award will provide important preliminary data for future larger clinical trials focused on optimizing corticosteroid use in pneumonia while training a junior investigator in the essential skills needed to become an independent researcher.