1. 1 COPD (Definitions + Pathology) Dr.Mohsen SHAHEEN Pneumologist Dr.Mohsen SHAHEEN Pneumologist

2. 2COPD High Morbidity Mortality

3. 3 Acommon respiratory disease A common respiratory disease Chronic Inflammation Small + Large Airways Fixed Airflow Limitation

4. COPD affects more than 5% of the population 4

5. It is the third-ranked cause of death in the US

6. Killing more than 120,000 individuals each year

7. is a High Chronic and Prevalence Disease COPD

8. The impact of COPD High Medical resource utilization Frequent clinician office visits

9. Frequent hospitalization s due to acute exacerbations Frequent hospitalization s due to acute exacerbations The impact of COPD

10. Need for chronic therapy Supplemental oxygen therapy Medications The impact of COPD

11. 11 Correct diagnosis of COPD is

12. 12  Symptoms (especially dyspnea)  Frequency and severity of exacerbations  Frequency and severity of exacerbations  Health status  Exercise capacity  Prolong survival

13. Definition of COPD 13

14. 14

15. 15 common Preventable treatable disease common Preventable and treatable disease NonCurable

16. 16 Progressive airflow limitation Chronic Bronchitis Emphysema Chronic Inflammation Small + Large airways Lung Exposure Toxic particles + Gazes Exposure  Toxic particles + Gazes

17. Chronic Bronchitis

18. 18 Chronic Productive Cough

19. For 3 months in each of two successive years In a patient in whom other causes of chronic cough (eg, bronchiectasis) have been excluded

20. Emphysema

21. 21 Trachea Primary Bronchus (BR) Bronchioles (BL) Terminal bronchioles (TBL) Conducting Zone Source: From Weibel 360

22. Respiratory Zone  Respiratory bronchioles (RBL)  Alveolar ducts (AD)  Alveolar sacs (AS)  Alveoli (300 million) Respiratory Zone  Respiratory bronchioles (RBL)  Alveolar ducts (AD)  Alveolar sacs (AS)  Alveoli (300 million)

23. Definition Emphysema Definition of Emphysema

24. Abnormal and permanent Enlargement of the airspaces distal to the terminal bronchioles 24

25. Destruction of the airspace walls without obvious fibrosis 25

26. Types of Emphysema 1. Pure emphysema 2. Emphysema + Mild Fibrosis 3. Interstitial Pneumonias + Emphysema

27. 4. Emphysema  Moderate or severe airflow obstruction ( more common) 4. Emphysema  Moderate or severe airflow obstruction ( more common) 5. Emphysema + Normal pulmonary Function 5. Emphysema + Normal pulmonary Function

28. Pathology of COPD

29. Pathology COPD Airways Lung parenchyma Pulmonary vasculature

30. COPD Is a Disease Characterized by Inflammation Cigarette smoke Epithelial cells CD8 + Tc cell Emphysema Proteases Mucus hypersecretion Macrophage/Dendritic cell Neutrophil Monocyte Fibroblast Obstructive bronchiolitis Fibrosis

31. Airway inflammation in COPD Neutrophilic inflammation  Numbers of Macrophages CD8 + T-lymphocytes

32. Neutrophilic inflammation

33. 33

36. Neutrophils Key effector cells in COPD Increasing cell numbers correlate with declining lung function

37. Neutrophils Infiltrating Bronchial Glands in COPD

38. Release mediators involved in neutrophil, monocyte and CD8 + cell to the lung Contribute to structural lung damage

39. 39 Are generated in the thymus and express the T-cell receptor

40. 40

41. 41 Orchestrate inflammatory process Effector cells that attract and enhance inflammatory function, e.g. in neutrophils and macrophages Increasing cell numbers correlate with loss of lung function

42. Release multiple inflammatory mediators 42

43. 43 Inflammatory Mediators in COPD proteases, TNF- , IL-8 Neutrophils Macrophages IL-8, IL-6 CD8 + T-cell IFN- , TNF-  Epithelial cell IL-8

44. Small airways 44

45. Small airways are usually defined as   Noncartilaginous airways with an internal diameter < 2mm Small airways are usually defined as   Noncartilaginous airways with an internal diameter < 2mm

46. These airways are located from approximately the eight generation of airways down to the alveoli

47. NormalNormal  Peripheral airway collapse Emphysema  Loss Of alveolar attachments

48.  Reduction in the number of small airways Small Airway

49. 49 Reproduced from The Lancet, Vol 364, Hogg JC. "Pathophysiology of airflow limitation in chronic obstructive pulmonary disease", pp709-721. Copyright © 2004, with permission from Elsevier. NormalCOPD Mucus Plug  numbers of:  Goblet cells  Mucus gland hyperplasia  numbers of:  Goblet cells  Mucus gland hyperplasia Mucus Plugging Obstructs Small Airways in COPD

50. Lung Parenchyma Lung Parenchyma 50

51. 51 Paraseptal Emphysema Distal Acinar

52. Paraseptal Emphysema

53. 53 Paraseptal Emphysema Distal Acinar Paraseptal Emphysema Distal Acinar

54. 54 Panlobular Emphysema Panacinar emphysema Panlobular Emphysema Panacinar emphysema alpha-1 antitrypsin deficiency

55. 55 Panlobular Emphysema

56. 56 Centrilobular emphysema Proximal acinar emphysema Centrilobular emphysema Proximal acinar emphysema

57. = upper lobes = apical region

58. Pulmonary vascular remodelling 58

59. Pulmonary vascular remodelling Begin early during the course of the disease

61. 1.Thickening of the vessel wall 2. Endothelial dysfunction 3.increased vascular smooth muscle Pulmonary vascular remodelling

62. 4.infiltration of the vessel wall by inflammatory cells: o Macrophages o CD8+ o T lymphocytes

63. 5.There is collagen deposition 6. Emphysematous destruction of the capillary bed

64. 64 Pulmonary vascular Remodeling Local hypoxia Pulmonary vasoconstriction (Chronic Hypoxemia) Pulmonary vasoconstriction (Chronic Hypoxemia) Reduction of the pulmonary vascular bed Blood hyperviscosity

65. Pulmonary Hypertension in COPD  Pulmonary vascular resistance Pulmonary vascular Remodelling

66. Cor Pulmonale Pulmonary Hypertension ++ Right Ventricular Dysfunction