Download CHRONIC OBSTRUCTIVE PULMONARY DISEASE UPDATE 2002

CHRONIC OBSTRUCTIVE
PULMONARY DISEASE UPDATE
2002
O. D. Polk, Jr., M.D.
Assistant Professor of Medicine
Howard University College of Medicine
IMPACT OF COPD IN THE US
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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.
COPD VS ASTHMA
Condition
Annual
mortality (N)
Estimate
annual cost
COPD
Asthma
100,000
5000-6000
$25 billion
$12 billion
Martin RJ. American Academy of Allergy, Asthma, and Immunology 56th
Annual Meeting; March 4, 2000; San Diego, Calif.
DEFINITION OF COPD
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Airflow limitation that is
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not fully reversible
usually progressive
Chronic abnormal inflammatory
response to
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environmental pollutants
irritants
tobacco smoke
American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120.
DIFFERENTIAL DIAGNOSIS
American Thoracic Society. Am J Respir Crit Care Med. 1995;152(suppl, pt 2):S77-S120.
RISK FACTORS FOR COPD
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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.
GENETIC RISK FACTORS FOR
COPD
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Accelerated decline in lung function
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15% of whites
5% of Asians
Alpha-1-Antitrypsin Deficiency (PiZZ)
Gentic polymorphisms of the TNF,
cytochrome p450, and miocrosomal
epoxide hydrolase
ALPHA1 –ANTITRYPSIN
DEFICIENCY (AAT)
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Patients with emphysema: <1%
Common variants: S and Z
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Point mutations in alpha1-antitrypsin gene
S-variant (264GluVal) in 28% of Southern Europeans
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Alpha1-antitrypsin levels = 60%
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no pulmonary effects
Z-variant (342Glu Lys) is associated with severe deficiency
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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.
PATIENT SELECTION FOR
SCREENING FOR THE
DIAGNOSIS OF AAT
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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
PATHOPHYSIOLOGY OF COPD
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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
CLINICAL FEATURES OF COPD
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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
SYMPTOMS OF COPD
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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.
PHYSICAL EXAMINATION FOR
COPD
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Airflow obstruction
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Hyperinflation of lungs
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Wheezing during auscultation
Prolongation of forced expiratory time
Low diaphragmatic position
Decreased intensity of heart and breath sounds
Severe disease
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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.
COPD – MANAGEMENT
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Smoking Cessation
Pharmacologic Therapy
Oxygen Therapy
Pulmonary Rehabilitation
Nutrition and COPD
Noninvasive Positive Pressure Ventilation
Surgery for COPD
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Lung Volume Reduction Surgery (LVRS)
Lung Transplantation
COPD RISK and SMOKING
CESSATION
Fletcher C and Peto R. Br Med J. 1977;1:1645-1648.
SMOKING CESSATION
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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
SMOKING CESSATON
INTERVENTION
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Physician Intervention – set a quit date
Refer to group smoking cessation clinics
Pharmacologic therapy with nicotine
replacement therapy (NRT) in highly
dependent smokers
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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
HOWARD UNIVERSITY
CANCER CENTER
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Tobacco Control Program
Ongoing Clinical Trial involving Smoking
Cessation
We are recruiting patients
Call
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202-865-4036
202-806-5293
PHARMACOLOGIC THERAPY
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Bronchodilators
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Short-acting
Long-acting
Corticosteroids
Mucolytics
Antibiotics
SHORT-ACTING
BRONCHODILATOR DRUGS
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Beta2-agonists and anticholinergics
Variable onset of action with duration of 4 to
6h
Improve symptoms and exercise capacity
Safe 3 to 4 times daily
Combining B2-agonists plus anticholinergic
drugs provides additional benefit to either
drug alone
SHORTACTING
BRONCHODILATORS
LONG-ACTING
BRONCHODILATOR DRUGS
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Drugs
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Salmeterol
Formoterol
Theophylline
Oral beta2-agonists
Duration of action usually lasts 12-24 h
Commonly used as maintenance
therapy in COPD
SYSTEMIC
CORTICOSTEROIDS
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10 TO 20% of patients with chronic COPD
improve
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Responders have more eosinophils in induced
sputum and bronchial biopsy
Treatment of hospitalized patients
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Fewer treatment failures
Shorter stays
More hyperglycemia
Two (2) weeks of therapy is sufficient
INHALED CORTICOSTEROIDS
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No short-term benefit
Long-term use may
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Improve lung function minimally
Improve 6-muinute walk test
Reduce moderate and severe (but not
mild) COPD exacerbations
MUCOLYTICS
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Variable effects in patients with COPD
Ineffective at shortening the course or
improving outcomes of patients with
acute exacerbations
ANTIBIOTICS
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Multiple trials favor the use of
antibiotics for acute exacerbations of
COPD
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Worsening dyspnea
Increased sputum volume
Sputum purulence
There is no evidence that prophylactic
antibiotics prevent acute exacerbations.
OXYGEN THERAPY IN COPD
OXYGEN THERAPY
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Two controlled trials – MRC and NOTT
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Death rates are lower
Quality of life indexes improved
Used for at least 15 hours/day
Oxygen should be prescribed when
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Arterial PaO2<55 mmHg or SaO2<88%
PaO2 56 to 59 mmHg
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ECG evidence of p pulmoonale
Pedal Edema/CHF
Secondary erythrocytosis
PULMONARY
REHABILITATION
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Improves dyspnea
Improves QOL scores
Reduces the number of hospitalizations
and days in the hospital
Effects on survival are not definite
NUTRITION AND COPD
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Malnutrition occurs in 1/4 to 1/3 of patients
with moderate to severe COPD
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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
SURGERY FOR COPD
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Lung volume reduction surgery (LVRS)
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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
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Procedure is costly
Limited lack of organs
Requires prolonged immunosuppression
NEW TREATMENTS
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Mediator Antagonists
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Protease Inhibitors
Antiinflammatory Drugs
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Leukotriene antagonists
TNF
Antioxidants
Phosphodiesterase 4 inhibitors
Drug Delivery
COPD: KEY POINTS
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Smoking cessation is extremely important.
None of the existing medications for COPD (with the
exception of oxygen) are known to modify the longterm 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