COPD

1. COPD Dr. Tanvir us Salam, FCCP Associate Professor of Medicine Post Graduate Medical Institute/LGH Lahore

2. Chronic Obstructive Pulmonary Diseases • Asthma • Chronic Bronchitis • Emphysema • Bronchiectasis • Cystic fibrosis

3. Definition • Asthma • Chronic inflammatory disorder of the airways • Airway obstruction • Recurrent and reversible • Atopy • Production of abnormal amounts of IgE antibodies in response to contact with aeroallergens • Airway Hyperresponsiveness • This is an abnormality of the airways that allows them to narrow too easily and too much

4. COPD • Chronic Bronchitis is defined by the presence of a productive cough for more than three months' duration in two successive years • Emphysema is a pathological definition, with enlargement of air spaces and destruction of lung parenchyma, loss of lung elasticity distal to terminal airways

5. Asthma • Chronic inflammatory disease of airway • Most common chronic disease of childhood • 5-10% of population are affected • More common in developed countries • 2:1 male/female ratio in childhood • Is asthma increasing? • Causing restricted activity and hospitalization • Death rate on the rise

6. COPD • 14 million people in the united states have COPD • 14 percent of white male smokers, as compared with approximately 3 percent of white male nonsmokers • COPD is now the sixth leading cause of death and it is the only common cause of death that is increasing in incidence • The world health organization predicts that by 2020 COPD will rise from its current ranking as the 12th most prevalent disease worldwide to the 5th and from the 6th most common cause of death to the 3rd

7. Relationship of Wheeze, Asthma, AHR Atopy Current asthma wheeze AHR

8. Plasma leakage Inflammatory cell recruitment and activation Mucus hypersecretion Virus-infected epithelium Airway Hyperresponsiveness Neural activation RV-Induced Airway Inflammation

9. Types • Persistent asthma • Obstructed asthma • Episodic asthma • Asthma in remission • Potential asthma • Trivial wheeze • Extrinsic/Atopic asthma • Occupational asthma • Intrinsic asthma

10. Inducers Allergens House dust mites Respiratory infections Passive smoking Genetics Trigger Allergens Exercise Infections Air pollution Weather Smells and irritants Emotional factors Food Risk Factors

11. Causes of Asthma Exacerbations

12. Pathological Features • Macroscopic features • Over inflated lungs • Wide spread plugging of the airways with thick secretions • Normal lung parenchyma

13. Pathologic Features • Microscopic features • Infiltration of epithelium with inflammatory cells • Shedding of the epithelium • Thickened basement membrane • Increased cells in lamina propria • Smooth muscle and mucous glands are hypertrophied

14. Cellular Mechanisms Involved in Airway Inflammation ANTIGEN IgE Mast cell B cell Macrophage Bronchospasm T cell Eosinophil Neutrophils Macrophage INFLAMATION

15. Pathophysiology • Reduction in airway diameter • Contraction of smooth muscles • Vascular congestion and edema of bronchial walls • Tenacious secretions • Increased airway resistance • Decreased forced expiratory volumes • Hyperinflation • Mismatched V/P

16. Molecular Genetics in COPD • In patients with (alpha)1-antitrypsin deficiency • Early emphysema develops that is exacerbated by smoking, indicating a clear genetic predisposition to COPD • However, less than 1 percent of patients with COPD have (alpha)1-antitrypsin deficiency

17. Molecular Genetics in COPD • A polymorphic variant of microsomal epoxide hydrolase, an enzyme involved in the metabolism of epoxides that may be generated in tobacco smoke, has been associated with a quintupling of the risk of COPD.

18. Risk Factors • In industrialized countries, cigarette smoking accounts for most cases of COPD • In developing countries other environmental pollutants, such as particulates associated with cooking in confined spaces, are important causes • Air pollution (particularly with sulfur dioxide and particulates), exposure to certain occupational chemicals (such as cadmium), and passive smoking may all be risk factors

19. Inflammation • Now apparent that there is a chronic inflammatory process in COPD • But it differs markedly from that seen in asthma, with different inflammatory cells, mediators, inflammatory effects, and responses to treatment • In contrast to the situation with asthma, eosinophils are not prominent except during exacerbations or in patients with concomitant asthma

20. Most inflammation in COPD occurs in the peripheral airways (bronchioles) and lung parenchyma. • The bronchioles are obstructed by fibrosis and infiltration with macrophages and T lymphocytes. • Destruction of lung parenchyma and an increased number of macrophages and T lymphocytes, which are predominantly CD8+ (cytotoxic) T cells.

21. Acute Exacerbations • It is now evident that many exacerbations in COPD, as in asthma, are due to upper respiratory tract viral infections (such as rhinovirus infection) and to environmental factors, such as air pollution and temperature. • There is an increase in neutrophils and in the concentrations of interleukin-6 and interleukin-8 in sputum during an exacerbation, and patients who have frequent exacerbations have higher levels of interleukin-6, even when COPD is stable.

22. Acute Exacerbations • Bronchial biopsies show no increase in sputum eosinophils during exacerbations in patients with severe COPD. • An increase in markers of oxidative stress and exhaled nitric oxide, presumably reflecting increased airway inflammation, is observed during exacerbations.

23. Development of disease Age of onset and diagnosis History of early life injury Progress of disease Present management Co-morbid condition Family history History of asthma, allergy, sinusitis, rhinitis, or nasal polyps in close relatives Social history Characteristics of home Smoking School characteristics Work place Level of education Medical History in Asthma

24. Aggravating factors All smokers! Viral respiratory infection Environmental allergens, indoor and out door Exercise Occupational chemicals Irritants Aggravating factors Emotional expressions Drugs Food, food additives and preservatives Change in weather, exposure to cold air Endocrine factors Medical History in COPD

25. Medical History both • Symptoms • Cough • Wheezing • Shortness of breath • Chest tightness • Fever • Sputum production

26. Physical Examination • Tachypnoea • Tachycardia • Pulsus Paradoxus • Cyanosis • Accessory muscle use • Prolonged expiration • Wheeze • Anxious look • Position and diaphoresis

30. Investigations • Chest x-ray • Sinuses x-ray • ECG • DLC (eosinophilia) • Sputum examination • Pulmonary function test • Spirometry • ABG • Pulse oximetery

37. Classification of Asthma Severity

38. Beta2-agonist Inhaled Short acting Long acting Oral Anticholinergics Methylxanthines Mast cell stabilizer Cromlyn sodium Nedocromil Corticosteroids Inhaled Systemic Leukotrine modifiers Treatment of Asthma

39. Therapeutic Measures in COPD • Antismoking Measures • Bronchodilators • Antibiotics • Oxygen • Corticosteroids • Noninvasive Ventilation • Pulmonary Rehabilitation • Lung-Volume-Reduction Surgery

40. Short Acting Inhaled Β2 Agonist • Indications • Relief of acute symptoms • Preventive prior to exercise • Mechanism • Smooth muscle relaxation • Adverse effects • Tachycardia, Skeletal muscle tremor, Hypokalemia, headache, increased lactic acid • Therapeutic issues • Drug of choice for acute spasm • Mild intermittent asthma

41. Long Acting Β2 Agonist • Indications • Long term prevention of symptoms, nocturnal • Not to be used to treat acute attack • Mechanisms • Smooth muscle relaxation • Inhibit mast cell mediator release • Onset ( 15-30 min.), Duration (>12 hours) • Adverse effects • QT prolongation • Other same as short acting • Therapeutic issues • Added to standard treatment with inhaled Corticosteroids

42. Systemic Β2 Agonist • Inhaled beta agonist are preferred because they have fewer side effect

43. Anticholinergics • Indication • Relief of acute symptoms • Mechanisms • Competitive inhibition of muscarinic cholinergic receptors • Reduces intrinsic vagal tone to the airways • Decrease mucus gland secretions • Adverse effects • Dry mouth and respiratory secretions • Therapeutic issues • Reverses only cholinergically mediated bronchospasm • Additive effect to β agonist • Treatment of choice for spasm induced by beta-blocker

44. Methylxanthines • Indications • Long tern control and prevention of symptoms, especially nocturnal symptoms • Mechanisms • Smooth muscle relaxation from phosphodiestrase inhibition • Increase diaphragm contractility and mucocilliary clearance • Adverse effects • Dose related toxiicities include tachycardia, nausea, vomiting SVT, headache, seizures • Usual doses include insomnia, gastric upset, increase in hyperactivity in children, difficulty in urination in elderly

45. Therapeutic Measures in COPD • Antismoking Measures • Bronchodilators • Antibiotics • Oxygen • Corticosteroids • Noninvasive Ventilation • Pulmonary Rehabilitation • Lung-Volume-Reduction Surgery

46. Antismoking Measures • Smoking cessation is the only measure that will slow the progression of COPD • Nicotine-replacement therapy (by gum, transdermal patch, or inhaler) provides help to patients in quitting smoking • The use of the recently introduced drug bupropion, a noradrenergic antidepressant, has proved to be the most effective strategy to date • A recent controlled trial showed that after a 9-week course of bupropion, abstinence rates were 30 percent at 12 months, as compared with only 15 percent with placebo • The abstinence rate was slightly improved with the addition of a nicotine patch.

47. Bronchodilators are the mainstay of current drug therapy for COPD.

48. Bronchodilators • Bronchodilators cause only a small (<10 percent) increase in FEV1 in patients with COPD • These drugs may improve symptoms by reducing hyperinflation and thus dyspnea • They may improve exercise tolerance, despite the fact that there is little improvement in spirometric measurements

49. Bronchodilators • Several studies have demonstrated the usefulness of the long-acting inhaled (beta)2-agonists salmeterol and formoterol in COPD. • An additional benefit of long-acting (beta)2-agonists in COPD may be a reduction in infective exacerbations, since these drugs reduce the adhesion of bacteria such as Haemophilus influenzae to airway epithelial cells.

50. Bronchodilators • COPD appears to be more effectively treated by anticholinergic drugs than by (beta)2-agonists, in sharp contrast to asthma, for which (beta)2-agonists are more effective. • A new anticholinergic drug, tiotropium bromide, which is not yet available for prescription, has a prolonged duration of action and is suitable for once-daily inhalation in COPD.