Study of Progression of Community Acquired Pneumonia in the Hospital in Patients With More Severe Preexisting Diseases and Immunosuppression

Pneumonia is a common infectious disease of the lung, often requiring treatment in the hospital. Clinical scoring systems are available, identifying patients not requiring hospitalization. However, the course of disease of patients in the hospital remains hard to predict. While most patients will recover quickly, some will, despite appropriate treatment, develop a severe course leading to sepsis and systemic responses resulting in organ dysfunction. The PROGRESS consortium aims to identify clinical, genetic, and other molecular markers and combinations there of predicting a severe course of pneumonia in the hospital. Such predictors will, for instance, support decisions on earlier transfer of patients to intensive care and thus improving outcome. PROGRESS-COMORB aims to extend findings from the previous PROGRESS study to patients with more severe preexisting conditions and immunosuppression.

Pneumonia is a common infectious disease of the lung, often requiring treatment in the hospital. Clinical scoring systems are available, identifying patients not requiring hospitalization. However, the course of disease of patients in the hospital remains hard to predict. While most patients recover quickly, others will, despite appropriate treatment, develop a severe course leading to sepsis and systemic responses resulting in organ dysfunction. The PROGRESS consortium aims to identify clinical, genetic and other molecular markers and combinations there of predicting a severe course of pneumonia in the hospital. Such predictors will, for instance, support decisions on earlier transfer of patients to intensive care and thus improving outcome. PROGRESS-COMORB aims to extend findings from the previous PROGRESS study to patients with more severe preexisting conditions and immunosuppression. In this observational, longitudinal case-cohort study, patients are enrolled within 48 hours of hospitalization (within 7 days for patients directly admitted to intensive care) and patient's progress is followed in much detail for up to six days thereafter. Further data are collected until discharge from the hospital. Patients are followed up on at days 28, 180, and 360 after enrollment. Baseline assessment comprises sociodemographic, anamnestic, family history, and life-style information. Upon enrollment, Pneumonia Severity Index (PSI) and CURB-65 are determined. For the day of enrollment, up to six subsequent study days routine laboratory and clinical observations and information on therapy are documented as well as data for determining the Sequential Organ Failure Assessment (SOFA) score, Systemic Inflammatory Response Syndrome (SIRS) status, and organ dysfunction. Starting with enrollment, up to four consecutive sets of biomaterials are collected comprising serum, plasma, and materials for extraction of RNA. Blood for extraction of DNA is collected once. Follow up comprises vital status, housing situation, recurrence of pneumonia, stroke, myocardial infarction, occurrence of diabetes and a quality of life questionnaire. In the PROGRESS consortium, the transition (progression) from uncomplicated community-acquired pneumonia acquired pneumonia (uCAP) to severe CAP (sCAP) to CAP with severe sepsis or septic shock or multiple organ failure (ssCAP) is investigated. Previous work of the PROGRESS consortium led to the successful identification of an operationalization for the severity of CAP and causal pathomechanistic correlations, a clinical prognosis score, the assignment of altered molecules to dysfunctions of the respiratory tract, kidneys, coagulation, cardiovascular system, and liver, and a gene expression signature for early detection of patients at risk of developing ssCAP. For the translation of findings from the PROGRESS-CAP study into clinical applicability, their applicability to CAP patients with immunosuppression or with more severe preexisting conditions has to be confirmed.