Background

hronic obstructive pulmonary disease (COPD) is a common and disabling condition in adults. Information about therapeutic effectiveness and adverse effects of common treatment options and how clinical and spirometric characteristics affect outcomes is not well known, but is important for clinicians caring for patients with stable COPD.

Purpose

To evaluate the effectiveness of COPD management strategies.

Data Sources

English-language publications in MEDLINE and the Cochrane Library through March 2007.

Study Selection

Randomized controlled trials (RCTs) and previous systematic reviews of inhaled therapies, pulmonary rehabilitation, disease management, and supplemental oxygen in adults with COPD.

Data Extraction

Participant, study, and intervention characteristics; exacerbations, deaths, respiratory health status, exercise capacity, hospitalizations, and adverse effects.

Data Synthesis

Eight meta-analyses and 42 RCTs examined inhaled therapies: short-acting anticholinergics (n = 7), long-acting anticholinergics (n = 10), long-acting [beta]₂-agonists (n = 22), corticosteroids (n = 14), dual D₂ dopamine receptor-[beta]₂-agonist (n = 3), or short-acting [beta]₂-agonist plus ipratropium (n = 3). Evidence for nonpharmacologic therapies included 3 reviews of 39 RCTs plus 6 additional RCTs of pulmonary rehabilitation, 2 reviews of 13 RCTs plus 2 additional RCTs of disease management, and 8 RCTs of oxygen. Overall, long-acting inhaled therapies, used alone or in combination, reduced exacerbations more than placebo by 13% to 25% and had similar effectiveness. Average improvements in health status scores were less than what is considered to be clinically noticeable. Inhaled monotherapy did not reduce mortality. Inhaled corticosteroids plus long-acting [beta]₂-agonists reduced deaths in relative terms when compared with placebo (relative risk = 0.82 [95% CI = 0.69-0.98]) and inhaled corticosteroids alone (relative risk = 0.79 [95% CI = 0.67-0.94]), but not when compared with long-acting [beta]₂-agonists alone (relative risk = 0.82 [95% CI = 0.52-1.28]). Absolute reductions were 1% or less and were not statistically significant. Pulmonary rehabilitation improved health status and dyspnea but not walking distance. Neither disease management nor ambulatory oxygen improved measured outcomes. Supplemental oxygen reduced mortality among symptomatic patients with resting hypoxia (relative risk = 0.61 [95% CI = 0.46-0.82]). Insufficient evidence supports the use of spirometry to guide therapy.

Limitations

Articles were limited to those in the English language. Treatment adherence, adverse effects, and effectiveness may differ among clinical settings. Short-acting inhalers for "rescue therapy" were not evaluated.

Conclusion

Long-acting inhaled therapies, supplemental oxygen, and pulmonary rehabilitation are beneficial in adults who have bothersome respiratory tract symptoms, especially dyspnea, and forced expiratory volume in 1 second (FEV₁) is less than 60% predicted.

Editor's Comments. This systematic review examines much of the available literature pertaining to various treatment components of COPD and applies current standard methods of evidence stratification. The conclusions of this data analysis form the basis of formal clinical practice guidelines under the aegis of the American College of Physicians (Qaseem et al. Ann Intern Med. 2007;147:633-638), which in summary are:

Recommendation 1: In patients with respiratory symptoms, particularly dyspnea, spirometry should be performed to diagnose airflow obstruction. Spirometry should not be used to screen for airflow obstruction in asymptomatic individuals. (Grade: strong recommendation, moderate-quality evidence.)

Recommendation 2: Treatment for stable COPD should be reserved for patients who have respiratory symptoms and FEV₁ of less than 60% predicted as documented by spirometry. (Grade: strong recommendation, moderate-quality evidence.)

Recommendation 3: Clinicians should prescribe one of the following maintenance monotherapies for symptomatic patients with COPD and FEV¹ of less than 60% predicted: long-acting inhaled [beta]₂-agonists, long-acting inhaled anticholinergics, or inhaled corticosteroids. (Grade: strong recommendation, high-quality evidence.)

Recommendation 4: Clinicians may consider combination inhaled therapies for symptomatic patients with COPD and FEV₁ of less than 60% predicted. (Grade: weak recommendation, moderate-quality evidence.)

Recommendation 5: Clinicians should prescribe oxygen therapy in patients with COPD and resting hypoxemia (Pao₂ <= 55 mm Hg). (Grade: strong recommendation, moderate-quality evidence.)

Recommendation 6: Clinicians should consider prescribing pulmonary rehabilitation in symptomatic individuals with COPD who have an FEV¹ of less than 50% predicted. (Grade: weak recommendation, moderate-quality evidence.)

Recommendation 6 is certain to be a bone of contention because the overall evidence in favor of pulmonary rehabilitation is arguably more robust than that for inhaled corticosteroids as monotherapy in patients with an FEV₁ of less than 60% predicted (recommendation 3) or that treatment be withheld in symptomatic patients unless the FEV₁ is less than 60% predicted (recommendation 2).-SK