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Julio A. Ramirez, MD, FACP Professor of Medicine Chief, Infectious Diseases University of Louisville Chief, Infectious Diseases Veterans Affairs Medical.

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Presentation on theme: "Julio A. Ramirez, MD, FACP Professor of Medicine Chief, Infectious Diseases University of Louisville Chief, Infectious Diseases Veterans Affairs Medical."— Presentation transcript:

1 Julio A. Ramirez, MD, FACP Professor of Medicine Chief, Infectious Diseases University of Louisville Chief, Infectious Diseases Veterans Affairs Medical Center Louisville, Kentucky, USA Clinical Outcomes in Patients with Community-Acquired Pneumonia

2 1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

3 Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Pathogenesis Alveolar Macrophage Capillary Pneumonia White Blood Cell Lymphatic

4 Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Alveolar Macrophage Capillary Pneumonia White Blood Cell Lymphatic Pneumonia Pathogenesis

5 Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Cytokines Pneumonia Generation of Cytokines White Blood Cell Lymphatic Pneumonia Pathogenesis

6 Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Cytokines Pneumonia Generation of Cytokines White Blood Cell Lymphatic Cytokines White Blood Cell Lymphatic Proinflammatory Cytokines Anti-inflammatory Cytokines Chemotactic Cytokines (Chemokines) CCL2 CCL3 CCL4 CCL5 CXCL1 (KC) CXCL10 (IP-10) IL-1 IL-1β IL-6 TNF-α G-CSF IFN-γ Interleukin-10 (IL-10) IL-1 receptor antagonist (IL-1ra) Pneumonia Pathogenesis

7 Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Activation of Neutrophils White Blood Cell Lymphatic Pneumonia Pathogenesis Local Inflammatory Response

8 Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Consolidation Phase Cytokines White Blood Cell Neutrophils Monocytes B / T cells Dendritic cells Lymphatic Fluid/Proteins Pneumonia Pathogenesis

9 Alveolar Macrophage Capillary Ramirez J. Community-Acquired Pneumonia. Lippincott Williams & Wilkins, 2003 Pneumonia Consolidation Phase Cytokines White Blood Cell Neutrophils Monocytes B / T cells Dendritic cells Lymphatic Fluid/Proteins Pneumonia Pathogenesis Local Inflammatory Response Systemic Inflammatory Response

10 Days 0 1 2 3 4 5 6 7 A A ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001 Diagnosis Local Inflammatory Response Systemic Inflammatory Response Severity of Disease Pneumonia Pathogenesis

11 Days 0 1 2 3 4 5 6 7 A A ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001 v Diagnosis FeverLeukocytosisCRPESRProcalcitonin CoughSputumTachypneaHypoxemiaInfiltrate Local Inflammatory Response Systemic Inflammatory Response Severity of Disease Pneumonia Pathogenesis

12 Days 0 1 2 3 4 5 6 7 A A ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001 v Diagnosis FeverLeukocytosisCRPESRProcalcitonin CoughSputumTachypneaHypoxemiaInfiltrate Local Inflammatory Response Systemic Inflammatory Response Severity of Disease Pneumonia Pathogenesis

13 1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

14 Days 0 1 2 3 4 5 6 7 Severity of Disease A A CAP: Clinical Outcomes

15 Days 0 1 2 3 4 5 6 7 Severity of Disease A A Clinical Response to Therapy CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

16 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease B B A A CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

17 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeteriorationLateClinicalDeteriorationLateClinicalDeterioration 3 3 4 4 B B A A CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

18 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A CAP: Clinical Outcomes ATS Guidelines for CAP. Am J Respir Crit Care Med 163:1730, 2001

19 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A CAP: Clinical Outcomes

20 Days Clinical Response Clinical Response Severity Severity of Disease of Disease CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes Point of Clinical Stability

21 Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Days CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes

22 Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Inflammatory Markers Markers Immune Response Immune Response Days CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes

23 Micro Response Micro Response Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Bacterial Bacterial Colony Colony Counts Counts Inflammatory Markers Markers Immune Response Immune Response Days CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes

24 Micro Response Micro Response Clinical Response Clinical Response X-ray Resolution X-ray Resolution Severity Severity of Disease of Disease Pulmonary Infiltrate Infiltrate Bacterial Bacterial Colony Colony Counts Counts Inflammatory Markers Markers Immune Response Immune Response Days Time to Switch Therapy CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: clinical, radiographic, immunologic, & microbiologic responses CAP: Clinical Outcomes Time to Clinical Stability Point of Clinical Stability Point of Switch Therapy

25 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A CAP: Clinical Outcomes

26 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A CAP: Clinical Outcomes

27 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A CAP: Clinical Outcomes

28 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes

29 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes CAP Severe CAP

30 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Aliberti S et al. Chest. 2008;134:955-962

31 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Aliberti S et al. Chest. 2008;134:955-962 Etiology of Failure 1. Severe Sepsis (33%)

32 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Etiology of Failure 1. Severe Sepsis (33%) 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B

33 LIR Local Infection Clinical Outcomes

34 LIRSIRS Local Infection CAP Clinical Outcomes

35 LIRSIRS Organ Dysfunction/FailureMODS Local Infection CAP Severe CAP Clinical Outcomes

36 LIRSIRS Organ Dysfunction/FailureMODS Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Local Infection Sepsis Severe Sepsis Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Mortality rates increase in patients >65yo (↓immunologic response to infection) Clinical Outcomes

37 LIRSIRS Organ Dysfunction/FailureMODS Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Mortality rates increase in patients >65yo (↓immunologic response to infection) Local Infection CAP Severe CAP Clinical Outcomes

38 Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG LIRSIRS Organ Dysfunction/FailureMODS Mortality rates increase in patients >65yo (↓immunologic response to infection) Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, CURB-65 Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Local Infection CAP Severe CAP PSI Clinical Outcomes

39 Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG LIRSIRS Organ Dysfunction/FailureMODS Mortality rates increase in patients >65yo (↓immunologic response to infection) Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Local Infection CAP Severe CAP CURB-65 PSI Clinical Outcomes

40 Respiratory RR>30, PO2<60, PA/FI<250, ARDS, MV Cardiovascular ↑HR, BP<90/60, Refractory Shock Renal ↓Urinary output, ↑BUN, ↑Creatinine CNS Mental status changes, Abnormal EEG LIRSIRS Organ Dysfunction/FailureMODS Mortality rates increase in patients >65yo (↓immunologic response to infection) Hematology Neutropenia, ↓Hb, Platelets<100K, DIC Metabolism ↑Glucose, ↓Temperature, ↓Ph, ↑Lactate, Local Infection CAP Severe CAP CURB-65 PSI Clinical Outcomes

41 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Clinical Failure: Severe Sepsis 30%

42 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Clinical Failure: AMI 20%

43 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Ramirez J et al. Clin Infec Dises. 2008;47:182-7 Clinical Failure: AMI 20%

44 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Ramirez J et al. Clin Infec Dises. 2008;47:182-7 Clinical Failure: AMI 20%

45 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Clinical Failure: AMI 20%

46 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Clinical Failure: Males vs Females

47 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes Clinical Failure: Males vs Females

48 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes

49 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes CAP due to Mycobacterium tuberculosis CAP due to Mycobacterium tuberculosis CAP complicated with empyema CAP complicated with empyema CAP associated with deterioration of CAP associated with deterioration of preexisting medical conditions (COPD, CHF) preexisting medical conditions (COPD, CHF)

50 EarlyClinicalImprovementEarlyClinicalImprovement 1 1 LateClinicalImprovementLateClinicalImprovement 2 2 Days 0 1 2 3 4 5 6 7 Severity of Disease EarlyClinicalDeteriorationEarlyClinicalDeterioration Nonresponding PneumoniaNonresponding Pneumonia LateClinicalDeteriorationLateClinicalDeterioration 3 3 5 5 4 4 B B A A Clinical Outcomes 100% 15% 45%25% 5% 10%

51 1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

52 1 2 3 4 5 6 7 Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP 2 3 4 CAP: Clinical Outcomes

53 1 2 3 4 5 6 7 Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes 2 3 4

54 1 2 3 4 5 6 7 Weeks Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP Re-hospitalization CAP: Clinical Outcomes Death 2 3 4

55 1 2 3 4 5 6 7 Weeks Days 2 3 4 ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP Re-hospitalization CAP: Clinical Outcomes Death Weeks 2 3 4 ClinicalImprovementClinicalImprovement B B AMI (+): 31% AMI (-): 10%

56 1 2 3 4 5 6 7 Weeks Days 2 3 4 ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP Clinical Cure: Resolution of S&S with resolution of pulmonary infiltrate CAP: Clinical Outcomes

57 1 2 3 4 5 6 7 Weeks Days 2 3 4 ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP (+) 624 CAP (-) 6,347 Long Term Survival: 5 years CAP: Clinical Outcomes

58 1 2 3 4 5 6 7 Weeks Days 2 3 4 ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes

59 1 2 3 4 5 6 7 Weeks Days 2 3 4 ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP (-) 6,347 CAP (+) 624 CAP: Clinical Outcomes

60 1 2 3 4 5 6 7 Weeks Days 2 3 4 ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP CAP: Clinical Outcomes

61 1 2 3 4 5 6 7 Weeks 1 2 3 4 5 Years Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement C C ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP 2 3 4 CAP Mortality: Days after diagnosis CAP Mortality: Weeks after diagnosis CAP Mortality: Years after diagnosis 1 2 3 4 5 6 7 Weeks 1 2 3 4 5 Years Days 2 3 4 Acute Systemic Inflammatory Disease CAP: Clinical Outcomes

62 1 2 3 4 5 6 7 Weeks 1 2 3 4 5 Years Days ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement C C ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement B B ClinicalDeteriorationClinicalDeterioration ClinicalImprovementClinicalImprovement A A CAP 2 3 4 CAP Mortality: Days after diagnosis CAP Mortality: Weeks after diagnosis CAP Mortality: Years after diagnosis 1 2 3 4 5 6 7 Weeks 1 2 3 4 5 Years Days 2 3 4 Acute Systemic Inflammatory Disease Chronic Systemic Inflammatory Disease? CAP: Clinical Outcomes

63 Pneumonia: Clinical Outcomes

64

65

66 1. CAP Pathogenesis 2. CAP Early Clinical Outcomes 3. CAP Late Clinical Outcomes CAP Clinical Outcomes

67


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