1. COPD SS Visser, Pulmonology Internal Medicine UP

2. Chronic Obstructive pulmonary Disease  Two distinct processes are involved, most often in combination.  Chronic Bronchitis – dx on history  Emphysema – dx previously on histology, nowadays clinically (good clinical-pathologic- radiologic correlation)

3. Def: Chronic Bronchitis  Excessive tracheobronchial mucus production sufficient to cause cough with expectoration for most days of at least 3 months of the year for 2 consecutive years.  Classification: 1.Simple chronic bronchitis 2.Chronic mucopurulent bronchitis 3.Chronic bronchitis with obstruction 4.Chronic bronchitis with obstruction and airway hyperreactivity.

4. Def: Emphysema  Permanent abnormal distention of air spaces distal to the terminal bronchiole with destruction of alveolar septa (containing alveolar capillaries) and attachments to the bronchial walls.  Classification: 1.Centriacinar ( centrilobular) emphysema 2.Panacinar emphysema 3.Paraseptal emphysema 4.Senile emphysema

6. Def: COPD  Chronic obstruction to airflow due to chronic bronchitis and/or emphysema.  Degree of obstruction may be less when the patient is free from respiratory infection and may improve with bronchodilator drugs  Significant obstruction is always present

7. Epidemiology of COPD  30% of smokers develop COPD  20% of adult males have COPD  15% of COPD patients are severely symptomatic  4 th leading cause of death (USA)  Mortality rate still rising   prevalence in low birth weight and low socioeconomic status  Tuberculosis in smokers predisposes to COPD

9. Pathogenesis:Effects of Smoking -1  Oxidative stress: O 2 -, OH -,H 2 O 2, HOCl; source of Fe 2+  catalizes production of OH - by neutrophils, eosinophils, alveolar macrophages; tar (cigarettes) contains NO and induces iNOS  toxic peroxynitrites  Elastin breakdown- activated neutrophils  neutrophil elastases and oxidants;  -1-AT and metalloproteinase inhibitors (lung defenses) inactivated by smoke  Chemoattractant, upregulation of adhesion molecules  neutrophil sequestration in lungs   expression of pro-inflammatory mediators: IL-8, NF-  B  recruitment of N, B, E and T lymphocytes

10. Effects of smoking -2   levels of myeloperoxidase and eosinophilic cationic protein  bronchoconstriction   levels of TGF-  (transforming growth factor)  fibrogenesis  Lipid peroxidation and DNA damage  point mutations 0f the p53 gene locus  epithelial dysplasia and lung cancer   ciliary function  retained secretions;  airway resistance  vagal-mediated smooth muscle contraction  Hypertrophy and hyperplasia of mucus secreting glands  secretions

12. Pathogenesis-3  Air pollution  exacerbations of CB related to heavy pollution with SO 2 and NO 2  Occupation  exposure to organic and inorganic dust or noxious gases  accelerated decline in lung function  Infection  even mild viral respiratory infections ( rhino virus) may be a major factor associated with etiology as well as progression of disease; severe viral pneumonia early in life may lead to COPD  Genetic factors: -  -1-antitrypsin deficiency PIZZ, PISZ, PI00 (PI null null),  susceptibility to effects of smoking

13. Pathophysiology  Air trapping- RV and FRC elevated  Hyperinflation –TLC elevated   elastic recoil pressure  dynamic collapse of airways during expiration  ineffective cough mechanism and pursed lips breathing (emphysema)   compliance (emphysema)   airway resistance  Prolonged forced expiratory time (N=<6 seconds)

14. Pathology: CB  Hypertrophy of mucus-producing glands in submucosa of large cartilaginous airways  Goblet cell hyperplasia, mucosal and submucosal inflammatory cell infiltrate, oedema, peribronchial fibrosis, intraluminal mucus plugs and increased smooth muscle in small airways  The major site of airflow obstruction is in the small airways and the inflammatory infiltrate consists of neutrophils (in asthma eosinophils)

15. Pathology : Emphysema   in number and size of alveolar fenestrae  eventual destruction of alveolar septa and their attachments to terminal and respiratory bronchioles  distention of alveolar spaces 1.Centriacinar E- respiratory bronchioles (central) affected 2.Panacinar E- central and peripheral portions of acinus affected 3.Senile E- alveoli and alveolar ducts enlarge (> 50 Y) 4.Periacinar/paraseptal E- distention of alveolar spaces adjacent to septal and pleural surfaces

16. Physical signs of COPD  Ronchi- in early disease present on forced expiration, later present in inspiration and expiration  Prolonged forced expiratory time (> 6 seconds)  Hyperinflation:  cardiac dullness, liver dullness displaced downwards,  A-P chest diameter,  heart and breath sounds, Hoover sign  Inspiratory crepitations (lung bases)  Pursed lips breathing (  dynamic airway collapse)  Use accessory respiratory muscles  Signs of cor pulmonale and PHT

17. Emphysema:ChronicBronchitis Emphysema = pink puffer Age (Dx) 60 + y Rest dyspneamild-mod Exer dyspneasevere Cough ± Sputum scanty, mucoid Resp infect less often Resp failure terminal Cor pulmonale terminal Chronic Bronchitis = blue bloater 50 ± y none moderate prominent large volume, purulent often repeatedly common

18. Emphysema:Chronic Bronchitis PHT (rest)0-mild (exertion)moderate Build Asthenic, cachectic Hematocrit35-45 Breath pattern use accessory muscles of respiration Sleep pattern Normal XRCHyperinflation Bullae Mild-moderate severe obese, cyanosed 50-55 do not use accessory muscles of respiration sleep apnea  bronchovascular markings

19. Emphysema:Chronic Bronchitis Blood gas: PaO 2 ± 65 mm Hg PaCO 2 35-40 Elastic recoil  AW resistance N-  Diffusion Cap  FEV1   Bronchodilator response Poor 45-60 50-60 Normal  N-   Better but < 12% and 200ml

27. Spirometric classification of COPD severity using post- bronchodilator FeV1  Stage I (Mild): FeV1/FVC <0.7; FeV1 80% of predicted  Stage II (Moderate): FeV1/FVC <0.7; FeV1 50- <80% of predicted  Stage III (Severe): FeV1/FVC <0.7; FeV1 30-<50%  Stage IV (Very severe): FeV1/FVC <0.7; FeV1 <30% or <50% but chronic respiratory failure is present. (GOLD 2007)

28. Treatment: Goals of management -1  Recognition of disease (early Diagnosis and staging)  Smoking cessation (secondary prevention) nicotine replacement and Zyban  Improvement of breathlessness (Rx of airflow obstruction- bronchodilator drugs) 1.Methylxanthines 2.Short and long-acting B 2 adrenergic agonists (  incidence of pneumonia with ICS and LABA combinations) 3.Short and long-acting Anticholinergics- BD of choice in COPD

29. Treatment -2  Respiratory infections –AB when  sputum volume and/or purulence (exacerbation of COPD); Influenza and Streptococcus pneumoniae vaccination  Bronchopulmonary drainage and postural drainage (physiotherapy) for patients with CB  Oxygen therapy for patients with hypoxia (PaO 2 55)  Pulmonary rehabilitation and education ( improving quality of life)- exercise program and improved nutrition  Prevention and treatment of complications (cor pulmonale) and limitation of disease progression

30. Treatment -3  Glucocorticoids –only 10% of COPD patients show subjective benefit and improved lung function (FeV1 increase of 20% or more) on systemic GCs; with COPD exacerbation a course of prednisone 40 mg/d for 2 weeks are usually prescribed  Inhaled GCs may  severity of exacerbations and need for hospitalisation. Benefit of 10-14 day trial of 30-40mg prednisone for Stage III COPD patients remains to be proven.  Lung volume reduction surgery  Transplantation

31. Airway Diseases - COPD  Smoking  Hyperinflation  Airway collapse  Respiratory infection  Bronchospasm  Allergy  Inflammation

32. Airway Diseases : Asthma  Allergy  Inflammation  Bronchospasm  Hyperinflation  Respiratory infection

33. AirwayDiseases:Bronchiectasis  Respiratory infection  Hyperinflation  Bronchospasm  Inflammation  Allergy