Chronic Obstructive Pulmonary Disease
HUIB A. KERSTJENS, M.D., Ph.D., and DIRKJE S. POSTMA, M.D., Ph.D., University Hospital Gronigen, Gronigen, The Netherlands
Questions Addressed
- What are the short- and long-term effects of maintenance drug treatment?
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Definition Chronic obstructive pulmonary disease (COPD) is airflow obstruction caused by chronic bronchitis or emphysema. Emphysema is abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. Chronic bronchitis is chronic cough or mucus production for at least three months in at least two successive years when other causes of chronic cough have been excluded.1
Incidence/Prevalence COPD mainly affects middle-aged and elderly people. It is one of the leading causes of morbidity and mortality worldwide. In the United States, it affects about 14 million people and is the fourth leading cause of death. Morbidity and mortality are rising. Estimated prevalence in the United States has risen by 41 percent since 1982, and age-adjusted death rates rose by 71 percent between 1966 and 1985. All-cause age-adjusted mortality declined over the same period by 22 percent, and mortality from cardiovascular diseases declined by 45 percent.1 In the United Kingdom, physician-diagnosed prevalence was 2 percent in men and 1 percent in women between 1990 and 1997.2
Etiology/Risk Factors COPD is largely preventable. The main cause is exposure to cigarette smoke. COPD is rare in lifetime nonsmokers (estimated incidence 5 percent in three large representative U.S. surveys from 1971 to 1984), in whom exposure to environmental tobacco smoke will explain at least some diseases.3,4 Other proposed causes include airway hyperresponsiveness, air pollution, and allergy.5-7
Prognosis Airway obstruction is usually progressive in those who continue to smoke, resulting in early disability and shortened survival. Smoking cessation reverts the rate of decline in lung function to that of nonsmokers.8 Many people will need medication for the rest of their lives, with increased doses and additional drugs during exacerbations.
Clinical Aims To alleviate symptoms, to prevent exacerbations, to preserve optimal lung function, and to improve activities of daily living, quality of life, and survival.9
Clinical Outcomes Short- and long-term changes in lung function, including changes in forced expiratory volume in one second (FEV1); exercise tolerance; peak expiratory flow rate; frequency, severity, and duration of exacerbations; symptom scores for dyspnea; quality of life; and survival.
Evidence-Based Medicine Findings
SEARCH DATE: CLINICAL EVIDENCEUPDATE SEARCH
AND APPRAISAL
JUNE 2001
This review deals only with treatment of stable COPD and not with treatment of acute exacerbations. Because we were interested in the maintenance treatment of stable COPD, we did not include single-dose or single-day cumulative dose response trials. Where randomized controlled trials (RCTs) were found, no systematic search for observational studies was performed.
Inhaled Anticholinergics
RCTs using a range of methods in people with COPD have found that anticholinergic drugs versus placebo improve FEV1 in the short term. One large RCT found that adding a long-term anticholinergic drug to a smoking cessation program had no significant impact on decline in FEV1.
Inhaled Beta2 Agonists
Short-term RCTs found that short- and long-acting inhaled beta2 agonists versus placebo significantly improved FEV1 and symptoms.
Beta2 Agonists Plus Anticholinergics
RCTs found that combining a beta2 agonist with an anticholinergic drug provided small additional bronchodilation compared with either drug alone.
Inhaled Beta2 Agonists vs. Anticholinergics
We found conflicting evidence from RCTs on the effects of inhaled beta2 agonists versus anticholinergics.
Theophyllines
We found limited evidence from small RCTs of a small bronchodilatory effect of theophyllines in people with COPD. Adverse effects are frequent.
Oral Corticosteroids
One systematic review of short-term RCTs has found that corticosteroid versus placebo significantly improves lung function. We found no RCT of the effects of long-term treatment on lung function. We found evidence of potentially serious adverse effects.
Inhaled Corticosteroids
RCTs found no evidence of benefit with short-term inhaled corticosteroids. Large RCTs lasting at least six months have found that inhaled steroids increase FEV1 during the first three to six months of use, but they found no subsequent effect on decline in lung function. One RCT also found that inhaled steroids versus placebo reduced the frequency of exacerbations and the rate of deterioration in quality of life.
Oral vs. Inhaled Steroids
Two RCTs found limited evidence suggesting that oral prednisolone was more effective than inhaled beclomethasone in people with mild to moderate COPD; one small RCT found no significant difference in response between treatments.
Mucolytics
Systematic reviews have found that long-term treatment with mucolytics versus placebo significantly reduces the frequency and duration of exacerbations.
Antibiotics
We found no RCTs of antibiotics in long-term treatment of stable COPD.
Domiciliary Oxygen
We found limited evidence that domiciliary oxygen treatment improved survival in people with COPD and hypoxemia. One RCT found that continuous treatment was more effective than nocturnal treatment.
Alpha1-Antitrypsin Infusion
One RCT found no significant difference between alpha1-antitrypsin versus placebo in the decline in FEV1 in people with alpha1-antitrypsin deficiency and moderate emphysema.
Deoxyribonuclease
We found no RCTs of deoxyribonuclease (DNase) in people with COPD.
Adapted with permission from Kerstjens HA, Postma DS. Chronic obstructive pulmonary disease. Clin Evid 2002;7:1344-57.
Both authors have received funding from the following manufacturers: AstraZeneca, Glaxo Wellcome, Boehringer Ingelheim, and Novartis, the manufacturer of formoterol. Dr. Postma has also received funding from Zambon.
REFERENCES
- American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152(5 pt 2)(suppl):77-120.
- Soriano JB, Maier WC, Egger P, et al. Recent trends in physician diagnosed COPD in women and men in the UK. Thorax 2000; 55:789-94.
- Whittemore AS, Perlin SA, DiCiccio Y. Chronic obstructive pulmonary disease in lifelong nonsmokers. Am J Public Health 1995; 85:702-6.
- Brunekreef B, Fischer P, Remijn B, van der Lende R, Schouten JP, Quanjer PH. Indoor air pollution and its effects on pulmonary function of adult non-smoking women. Int J Epidemiol 1985;14:227-30.
- Rijcken B, Weiss ST. Longitudinal analyses of airway responsiveness and pulmonary function decline. Am J Respir Crit Care Med 1996;154(suppl):246-9.
- Dockery DW, Brunekreef B. Longitudinal studies of air pollution effects on lung function. Am J Respir Crit Care Med 1996;154 (suppl):250-6.
- O'Connor GT, Sparrow D, Weiss ST. The role of allergy and non-specific airway hyperresponsiveness in the pathogenesis of chronic obstructive pulmonary disease. Am Rev Respir Dis 1989;140:225-52.
- Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. JAMA 1994; 272:1497-1505.
- Siafakas NM, Vermeire P, Pride NB, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995;8:1398-1420.
This is one in a series of chapters excerpted from Clinical Evidence, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence is published in print twice a year and is updated monthly online. The complete text for this topic, as well as additional information, is available to subscribers at www.clinicalevidence.com. This series is part of the AFP's CME. See "Clinical Quiz" on page 725.
