The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelinesare used to guide clinical practices for treating Chronic Obstructive Pulmonary Disease (COPD). GOLD focuses heavily on stable COPD patients, limiting its use fornon-stable COPD patients such as those with severe, acute exacerbations of COPD (AECOPD) that require hospitalization. Although AECOPD can be heterogeneous, it can lead to deterioration of health and early death. Electronic health records (EHRs) can be used to analyze patient data for understanding disease progression and generating guideline evidence for AECOPD patients. However, because of its structure and representation, retrieving, analyzing, and properly interpreting EHR data can be challenging, and existing tools do not provide granular analytic capabil-ities for this data.<div><br></div><div>This dissertation presents, develops, and implements a novel approach that systematically captures the effect of interventions during patient medical encounters, and hence may support evidence generation for clinical guidelines in a systematic and principled way. A conceptual framework that structures components, such as data storage, aggregation, extraction, and visualization, to support EHR data analytics for granular analysis is introduced. We develop a software framework in Python based on these components to create longitudinal representations of raw medical data extracted from the Medical Information Mart for Intensive Care (MIMIC-III) clinical database. The software framework consists of two tools: Patient Aggregated Care Events (PACE), a novel tool for constructing and visualizing entire medical histories of both individual patients and patient cohorts, and Mark SIM, a Markov Chain Monte Carlo modeling and simulation tool for predicting clinical outcomes through probabilistic analysis that captures granular temporal aspects of aggregated, clinicaldata.<br></div><div><br></div><div>We assess the efficacy of antibiotic treatment and the optimal time of initiationfor in-hospitalized AECOPD patients as an application to probabilistic modeling. We identify 697 AECOPD patients of which 26.0% were administered antibiotics. Our model simulations show a 50% decrease in mortality rate as the number of patients administered antibiotics increase, and an estimated 5.5% mortality rate when antibiotics are initially administrated after 48 hours vs 1.8% when antibiotics are initially administrated between 24 and 48 hours. Our findings suggest that there may be amortality benefit in initiation of antibiotics early in patients with acute respiratory failure in ICU patients with severe AECOPD.<br></div><div><br></div><div>Thus, we show that it is feasible to enhance representation of EHRs to aggregate patients’ entire medical histories with temporal trends and support complex clinical questions to drive clinical guidelines for COPD.<br></div>