Chronic Obstructive Pulmonary Disease

1. Chronic Obstructive Pulmonary Disease E. Sevda Özdoğan MD Chest diseases

2. COPD • COPD is a disease state characterized by airflow limitation (obstruction) that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

3. Terminology • Chronic Bronchitis Defined as the presence of cough and sputum production for at least 3 months in each of 2 consecutive years, is not necessarily associated with airflow limitation. • Emphsema Irreversibl dilatation and destruction of the airways distal to terminal bronchie (without fibrosis) • Centrlobular emphysema (respiratory bronchioles) • Panlobular emphsema (resp. Br+alv ductus and alveolus)

4. Normallung COPD

5. Epidemiology • Chronic Obstructive Pulmonary Disease (COPD) is a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States and is projected to rank fifth in 2020 as a worldwide burden of disease • Prevalance is higher among men (9.3 versus 7.3/1000) • Prevelance is increasing with age • Smoking is the main cause! • As life expectancy increases the economic cost of the disease also increase

6. Environmental Smoking (active, passive) Responsible from 80-90% of COPD) RR for Chronic bronchitis among smokers is 50 %, COPD 15-20 % Occupational exposures Miners (kadmiyum,silica) bakers, construction, wood workers Grain dust Wool Air pollution Social factors Dietary factors Low Antioxidans and vitamin (A,C,E;Mg) High salt Host related Genetic factors (%1) Alfa-1 antitripsin deficiency (otozomal recessive) Family history Age Childhood viral infections (RSV,Adenovirüs) Bronchial hyperreactivity Atophy Low birth weight RİSK FACTORS İN COPD

7. Pathophysiological Mechanisms • Inflammation • Protease-antiprotease imbalance • Oxydative stress

8. CELLULAR MECHANISMS OF COPD Cigarette smoke Alveolar macrophage ? CD8+ MCP-1 lymphocyte Neutrophil chemotactic factors Cytokines (IL-8) Mediators (LTB4) 4 ) ) Neutrophil PROTEASE INHIBITORS Neutrophil elastase - PROTEASES Cathepsins Matrix metalloproteinases Alveolar wall destruction Mucus hypersecretion (Emphysema) (Chronic bronchitis)

9. REACTIVE OXYGEN SPECIES IN COPD ANTIOXIDANTS Vitamins C and E N-acetylcysteine Glutathione analogues Anti-proteases Nitrones (spin trap) SLPI 1-AT NF-B Proteolysis IL-8 TNF- a O2-, H202 OH., ONOO- Neutrophil recruitment Mucus secretion Isoprostanes Bronchoconstriction Plasma leak

11. Sites of pathological changes • Central airways • Peripheral airways • Remodeling! Irreversibl! • Lung parenchyma • Emphysema • Pulmonary vasculature • Respiratory muscles • Respiratory center

12. Pulmonary vasculature • Paranchymal destruction vascular destruction • Hypoxia vasoconstruction intimal and muscle thickening • Hypoxia polistemia trombosis Pulmonary hypertension Corpulmonale (Pulmonary heart disease)

13. Respiratory muscles • Increased respiratory work • Skeletal muscle disfunction • Atrophy • Drug side effects • Nutritional problems Cachexia

14. Respiratory center • Inequality in the V/Q ratio V/Q dead space ventilation V/Q shunt effect • Hypoxia • Hypercapnia Tachypnea

15. Physiology • Diminished ability of the airways to remain open during expiration • Ventilation/perfusion inequality • Air trapping

16. Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS cough tobacco sputum occupation dyspnea indoor/outdoor pollution è SPIROMETRY

17. Physical examination • Expiratory dyspnea, tachypnea • Prolonged expiration (>6 sec), • Accessory muscle activity, pursed lip respiration • Cyanosis • Wheesing, ronchus silent chest • Barrel chest (Emphysema) • Hypersonority • Corpulmonale signs • Flapping tremor (Hypercapnia)

18. Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS cough tobacco sputum occupation dyspnea indoor/outdoor pollution è SPIROMETRY

19. Spirometry: Normal and COPD

20. FEV1/FVC<%70 • FEV1 is used for the classification of severity • Decreased FEF 25-75 (MMFR) • Increased airway resistance (RAV) • Decreased MVV • Decreased MIP, MEP • Decreased DLCO and DLCO/VA in emphysema

21. Reversibility test • Chest radiology • Normal • Emphysema • Pulmonary hypertension • Blood gas Measurement of arterial blood gas tension should be considered in all patients with FEV1 < 40% predicted or clinical signs suggestive of respiratory failure or right heart failure.

26. Routine blood tests: • Polistemia • Liver function abnormality • Renal function abnormalities • ECG: • Axis changes due to diafragmatic flattening or right ventricular hypertrophy • P pulmonale • Right bundle block • İmpaired R progression

27. Alfa-1 antitripsin deficiency tests: • COPD before the age of 45 • Family history • Nonsmokers • Panlobular emphysema in the lower lobes

28. Pulmonary Hypertension in COPD • Decreased pulmonary vascularity • Hypoxemia-pulmonary vasoconstruction • Polistemia and increased blood viscosity • Pulmonary thrombosis • Hypoxemia- decreased renal blood supply-fluid retantion

29. Physical signs of Corpulmonale • Conjunctival hyperemia • Cyanosis • Peripheral edema (Pretibial) • Enlarged liver • Venous enlargement on the neck

30. Radiologic signs of corpulmonale • Cardiomegaly • Increased vascular arborization • Enlarged pulmonary artery of right hilum (over 14-16 mm) • Enlargement in main pulmonary artery • Costophrenic dullness- pleural effusion

32. Classification of COPD Stage Characteristics 0: At risk Normal spirometry Chronic symptoms (cough, sputum)  I: Mild FEV1/FVC < 70%; FEV1 ³ 80% predicted With or without symptoms (cough, sputum) II: Moderate FEV1/FVC < 70%; 50% £ FEV1 < 80% predicted III: Severe FEV1/FVC < 70%; 30% £ FEV1 < 50% predicted With or without chronic symptoms (cough, sputum, dyspnea) IV:Very SevereFEV1/FVC < 70%; FEV1 < 30% predicted or FEV1 < 50%predicted plus respiratory failure or clinical signs of right heart failure

33. COPD Exacerbations • Exacerbations: • Increased dyspnea • Increased cough and sputum • Purulance in sputum (Sometimes drowsiness, high fever etc) • The most common causes of an exacerbation are infection of the tracheobronchial tree (80%) and; s pneumonia; h influensae; m catarrhalis; are the most common pathogens (viruses less common)

34. Tracheobronchial infections Air pollution Pneumonia Pulmonary embolism Pneumothorax Thorax trauma Code fractures Beta blockers narcotic use Arhytmia Cardiac failure Main Causes of exacerbations

35. Severe exacerbation • Cyanosis • RR>25 • HR>110/dk • Somnolence • Severe deteoriation in PFT • Pneumonia, pneumotorax • Confusion, coma, arrest • PO2<50, PCO2>70, pH<7.35 Intensive care indication

36. Objectives of COPD Management • Prevent disease progression • Relieve symptoms • Improve exercise tolerance • Improve health status • Prevent and treat exacerbations • Prevent and treat complications • Reduce mortality • Minimize side effects from treatment

37. Smoking cessationis the single most effective-and cost-effective- intervention to reduce the risk of developing COPD and stop its progression

38. Pharmacologic treatment • Can improveandpreventsymptoms, • Reducethefrequencyandseverity of exacerbations, • Improvehealthstatus, • Improveexercisetolerance.

39. Non-Pharmacologic Treatment • Rehabilitation • Oxygen therapy • NIMV, IMV • Surgical interventions

41. COPD IS NOT ASTHMA ! • Different causes • Different age • Different inflammatory cells and consequences • Differences in syptomatology • Different response to treatment

42. ASTHMA vs COPD INFLAMMATION ASTHMA COPD CellsMast cells Eosinophils Neutrophils CD4+ T cells CD8+ T cells Macrophages +Macrophages +++ Mediators LTD4, histamineLTB4 IL-4, IL-5IL-8, TNF- ROS + ROS +++ Effects All airways Periph airways Lung destruction Little fibrosisFibrosis + Ep shedding Sq metaplasia Response to steroids +++

43. CongestiveHearthFailure PND Crackles Known cardiac pathology Cardiac dilatation (enlargement) on chest x ray Restrictive pulmonary functions

44. Bronchiectasis Bronchiectasis is irreversible destruction abnormal dilatation in one or more bronchi due to the damage in muscle and elastic tissue Recurrent infections in the bronchiectatic lung cause the typical clinical findings Bronchiectasis shares many clinical features with chronic obstructive pulmonary disease (COPD), including inflamed and easily collapsible airways, obstruction to airflow, and frequent office visits and hospitalizations.

45. Etiology Airway obstruction (eg, foreign body aspiration, tumour, adenoma), Severe pulmonary infections in early chilhood Whooping cough (pertusis) Defective host defenses and recurrent infections Cystic fibrosis, Young's syndrome, Rheumatic and systemic diseases, (rheumatoid arthritis (RA) and Sjögren's syndrome) Dyskinetic cilia,

46. Allergic bronchopulmonary aspergillosis (ABPA), Cigarette smoking. Alpha-1 antitrypsin deficiency 

47. Symptoms Cough (98 percent of patients), Heavy sputum production (78 percent), Dyspnea (62 percent), Rhinosinusitis (73 percent), Hemoptysis (27 percent),

48. Physical findings Crackles (75 percent) and Wheezing (22 percent) Digital clubbing (2 percent)

49. The diagnosis is usually established clinically on the basis of chronic daily cough with viscid large amount of sputum production, and radiographically by the presence of bronchial wall thickening and luminal dilatation on chest computed tomographic (CT) scans