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 :362.

3. COPD VS ASTHMA Annual Estimate Condition mortality (N) annual cost
COPD 100,000 $25 billion
Asthma $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-S Mahadeva R and Lomas DA. Thorax. 1998;53:
Global Initiative for Chronic Obstructive Lung Disease. NHLBI/WHO Workshop Report. April 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:

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 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 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:

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

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
Salmeterol
Formoterol
Theophylline
Oral beta2-agonists
Duration of action usually lasts 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 Protease Inhibitors
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