CHRONIC OBSTRUCTIVE PULMONARY DISEASE UPDATE 2002

1. CHRONIC OBSTRUCTIVE PULMONARY DISEASE UPDATE 2002 O. D. Polk, Jr., M.D. Assistant Professor of Medicine Howard University College of Medicine

2. IMPACT OF COPD IN THE US • Affects 21.7 million Americans • The fourth leading cause of death – 112,000 deaths in 1998 • Annual cost >$30 billion – $14.7 billion in direct healthcare costs – $15.7 billion in indirect healthcare costs • It is estimated that by 2020 COPD will be the third leading cause of death in the world Data on file (analysis of NHANES III data), GlaxoSmithKline. American Lung Association. Fact sheet: chronic obstructive pulmonary disease (COPD). Murphy SL. National Vital Statistics Reports; 48(11); 2000. Murray CJL and Lopez AD, eds. The Global Burden of Disease. Vol. 1. 1996:362.

3. COPD VS ASTHMA Annual Estimate Condition mortality (N) annual cost COPD 100,000 $25 billion Asthma 5000-6000 $12 billion Martin RJ. American Academy of Allergy, Asthma, and Immunology 56th Annual Meeting; March 4, 2000; San Diego, Calif.

4. DEFINITION OF COPD • Airflow limitation that is • not fully reversible • usually progressive • Chronic abnormal inflammatory response to • environmental pollutants • irritants • tobacco smoke American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120.

5. DIFFERENTIAL DIAGNOSIS American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120.

6. RISK FACTORS FOR COPD • Tobacco smoking (80% to 90%) • Passive smoking • Ambient air pollution • Hyperresponsive airways • Exposure to occupational dusts and chemicals • Indoor/outdoor air pollution • Alpha1-antitrypsin deficiency (<1%) American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120. Mahadeva R and Lomas DA. Thorax. 1998;53:501-505. Global Initiative for Chronic Obstructive Lung Disease. NHLBI/WHO Workshop Report. April 2001. NIH publication 2701.

7. GENETIC RISK FACTORS FOR COPD • Accelerated decline in lung function • 15% of whites • 5% of Asians • Alpha-1-Antitrypsin Deficiency (PiZZ) • Gentic polymorphisms of the TNF, cytochrome p450, and miocrosomal epoxide hydrolase

8. ALPHA1 –ANTITRYPSIN DEFICIENCY (AAT) • Patients with emphysema: <1% • Common variants: S and Z • Point mutations in alpha1-antitrypsin gene • S-variant (264GluVal) in 28% of Southern Europeans • Alpha1-antitrypsin levels = 60% • no pulmonary effects • Z-variant (342Glu Lys) is associated with severe deficiency • Levels » 10% of normal • Accumulation of alpha1-antitrypsin in the rough endoplasmic reticulum of the liver • Predisposed to juvenile hepatitis, cirrhosis, and hepatocellular carcinoma Mahadeva R and Lomas DA. Thorax. 1998;53:501-505.

9. PATIENT SELECTION FOR SCREENING FOR THE DIAGNOSIS OF AAT • Onset of COPD before age 50 • COPD without smoking history • Family history of COPD under age 50 • Smoker with family history of COPD • Young adult asthmatic unresponsive to therapy • Patient with predominant lower lobe emphysema

10. PATHOPHYSIOLOGY OF COPD • Hallmark – limitation of expiratory flow with relative preservation of inspiratory flow • Bronchial hyperresponsiveness – strong predictor of progression of airway obstruction • Nonuniform ventilation • Hyperinflation • Increased work of breathing and dyspnea

11. CLINICAL FEATURES OF COPD • Typical smokers—mean 20 cigarettes/day for 20 years • Usually present in fifth decade of life with productive cough or acute chest illness • Dyspnea with exertion • History of wheezing and dyspnea may lead to an erroneous diagnosis of asthma

12. SYMPTOMS OF COPD • Chronic cough • Sputum production • Breathlessness (dyspnea with exertion) • Wheezing American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120.Global Initiative for Chronic Obstructive Lung Disease. NHLBI/WHO Workshop Report.April 2001. NIH Publication 2701.

13. PHYSICAL EXAMINATION FOR COPD • Airflow obstruction • Wheezing during auscultation • Prolongation of forced expiratory time • Hyperinflation of lungs • Low diaphragmatic position • Decreased intensity of heart and breath sounds • Severe disease • Pursed-lip breathing • Use of accessory respiratory muscles • Retraction of intercostal spaces American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120.Global Initiative for Chronic Obstructive Lung Disease. NHLBI/WHO Workshop Report.April 2001. NIH Publication 2701.

14. COPD – MANAGEMENT • Smoking Cessation • Pharmacologic Therapy • Oxygen Therapy • Pulmonary Rehabilitation • Nutrition and COPD • Noninvasive Positive Pressure Ventilation • Surgery for COPD • Lung Volume Reduction Surgery (LVRS) • Lung Transplantation

15. COPD RISK and SMOKING CESSATION Fletcher C and Peto R. Br Med J. 1977;1:1645-1648.

16. SMOKING CESSATION • Smoking cessation is the only measure that will slow the progression of COPD (the Lung Health Study) • The presence of respiratory illness such as COPD is not a motivator for smoking cessation • Physician-delivered smoking cessation interventions can significantly increase smoking abstinence rates

17. SMOKING CESSATON INTERVENTION • Physician Intervention – set a quit date • Refer to group smoking cessation clinics • Pharmacologic therapy with nicotine replacement therapy (NRT) in highly dependent smokers • Smokes a pack or more per day • Requires 1st cigarette within 30 min of waking up • Finds it difficult refraining from smoking in places where it is forbidden • Consider therapy with bupropion alone or in combination with NRT

18. HOWARD UNIVERSITY CANCER CENTER • Tobacco Control Program • Ongoing Clinical Trial involving Smoking Cessation • We are recruiting patients • Call • 202-865-4036 • 202-806-5293

19. PHARMACOLOGIC THERAPY • Bronchodilators • Short-acting • Long-acting • Corticosteroids • Mucolytics • Antibiotics

20. SHORT-ACTING BRONCHODILATOR DRUGS • Beta2-agonists and anticholinergics • Variable onset of action with duration of 4 to 6 h • Improve symptoms and exercise capacity • Safe 3 to 4 times daily • Combining B2-agonists plus anticholinergic drugs provides additional benefit to either drug alone

21. SHORTACTING BRONCHODILATORS

22. LONG-ACTING BRONCHODILATOR DRUGS • Drugs • Salmeterol • Formoterol • Theophylline • Oral beta2-agonists • Duration of action usually lasts 12-24 h • Commonly used as maintenance therapy in COPD

23. SYSTEMIC CORTICOSTEROIDS • 10 TO 20% of patients with chronic COPD improve • Responders have more eosinophils in induced sputum and bronchial biopsy • Treatment of hospitalized patients • Fewer treatment failures • Shorter stays • More hyperglycemia • Two (2) weeks of therapy is sufficient

24. INHALED CORTICOSTEROIDS • No short-term benefit • Long-term use may • Improve lung function minimally • Improve 6-muinute walk test • Reduce moderate and severe (but not mild) COPD exacerbations

25. MUCOLYTICS • Variable effects in patients with COPD • Ineffective at shortening the course or improving outcomes of patients with acute exacerbations

26. ANTIBIOTICS • Multiple trials favor the use of antibiotics for acute exacerbations of COPD • Worsening dyspnea • Increased sputum volume • Sputum purulence • There is no evidence that prophylactic antibiotics prevent acute exacerbations.

27. OXYGEN THERAPY IN COPD

28. OXYGEN THERAPY • Two controlled trials – MRC and NOTT • Death rates are lower • Quality of life indexes improved • Used for at least 15 hours/day • Oxygen should be prescribed when • Arterial PaO2<55 mmHg or SaO2<88% • PaO2 56 to 59 mmHg • ECG evidence of p pulmoonale • Pedal Edema/CHF • Secondary erythrocytosis

29. PULMONARY REHABILITATION • Improves dyspnea • Improves QOL scores • Reduces the number of hospitalizations and days in the hospital • Effects on survival are not definite

30. NUTRITION AND COPD • Malnutrition occurs in 1/4 to 1/3 of patients with moderate to severe COPD • Depletion of fat mass and fat-free mass • Elevated resting energy expenditure • Nutritional supplements alone do not reverse weight loss • Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients but did not improve respiratory muscle function

31. SURGERY FOR COPD • Lung volume reduction surgery (LVRS) • Mortality 0 to 6% 30 days postop • Mortality 0 to 8% 6 months postop • Ongoing trials will provide cost-benefit analysis • Resection of large bullae • Lung Transplantation • Procedure is costly • Limited lack of organs • Requires prolonged immunosuppression

32. NEW TREATMENTS • Mediator Antagonists • Leukotriene antagonists • TNF • Antioxidants • Protease Inhibitors • Antiinflammatory Drugs • Phosphodiesterase 4 inhibitors • Drug Delivery

33. COPD: KEY POINTS • Smoking cessation is extremely important. • None of the existing medications for COPD (with the exception of oxygen) are known to modify the long-term prognosis of this disease • Pharmacotherapy for COPD is used for the overall management of the disease (including improvement of lung function and QOL) • Bronchodilator medications are central to the symptom management of COPD. They are given on an as-needed basis or as maintenance therapy