Study of Progression of Community Acquired Pneumonia in the Hospital

Study Overview
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Brief Summary
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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 study aims to identify clinical, genetic, and other molecular markers and combinations thereof 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.

Detailed Description
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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 study aims to identify clinical, genetic and other molecular markers and combinations thereof 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. The PROGRESS study was initially approved by the ethics board of the University Hospital Jena, Friedrich-Schiller-University Jena, Germany (2403-10/08, November 6th, 2008) and subsequently by the ethics committees of all recruiting study centers. In this observational, longitudinal case-cohort study, patients are enrolled within 48 hours of hospitalization 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 live style information. Upon enrollment, Pneumonia Severity Index (PSI) and CURB-65 are determined. For the day of enrollment and 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 six 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, and a quality of life questionnaire. Analysis of cross sectional and time series data will identify clinical, genetic, and other molecular markers predicting a severe course of pneumonia in the hospital. Analysis of multilevel 'omics data in conjunction with clinical data will provide new insights into pathomechanistic details of pneumonia progression.

Official Title
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Study of Progression of Hospitalized Community Acquired Pneumonia - Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis

Conditions
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Pneumonia, Sepsis, Shock, Septic

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalization with community acquired pneumonia (CAP) confirmed by pulmonary infiltrate in chest radiograph Working diagnosis of CAP by enrolling physician Adult patient >= 18 years of age Valid informed consent form At least 2 out of the five following clinical symptoms: Fever Cough Purulent sputum Shortness of breath or need for respiratory support Crackling or rales on auscultation, dullness to percussion, or bronchial breathing Exclusion Criteria: Participation in this study at an earlier time Hospitalization for any reason within 28 days prior to hospitalization for the current episode of CAP More than 48 hours in the hospital before enrollment Pregnancy Breastfeeding Decision on limitation of therapy before enrollment Known HIV infection or AIDS Anti-tumor treatment within the past six months Post-stenotic pneumonia in conjunction with bronchial carcinoma Therapy with corticosteroids ≥ 20mg for ≥ 14 days before enrollment Non-steroidal immunosuppressive therapy within the past six months Cytostatic therapy within the past six months Radiation therapy within the past six months Bone marrow transplant received Respiratory support at home via tracheostoma Cystic fibrosis Active tuberculosis Acute lung injury or acute respiratory distress syndrome for extrapulmonary reasons Massive aspiration Sepsis with extrapulmonary focus Acute pulmonary embolism Congestive heart failure New York Heart Association (NYHA) IV stadium Liver insufficiency Child-Pugh C stadium

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst measure of disease severity | Disease severity is operationalized by the Sequential Organ Failure Assessment (SOFA-score). | Between enrollment and day six | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality |  | up to one year after enrolment | 
| disease-specific mortality |  | up to one year after enrolment | 
| duration of hospitalization |  | up to one year after enrolment | 
| duration of intensive care treatment |  | up to one year after enrolment | 
| duration of ventilator assisted breathing |  | up to one year after enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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community acquired pneumonia, CAP, disease progression