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Scientific Review

Don D. Sin, MD, MPH; Finlay A. McAlister, MD, MSc; S. F. Paul Man, MD; Nick R. Anthonisen, MD, PhD

JAMA. 2003;290:2301-2312.

Context  The care of patients with chronic obstructive pulmonary disease (COPD) has changed radically over the past 2 decades, and novel therapies can not only improve the health status of patients with COPD but also modify its natural course.

Objective  To systematically review the impact of long-acting bronchodilators, inhaled corticosteroids, nocturnal noninvasive mechanical ventilation, pulmonary rehabilitation, domiciliary oxygen therapy, and disease management programs on clinical outcomes in patients with COPD.

Data Sources  MEDLINE and Cochrane databases were searched to identify all randomized controlled trials and systematic reviews from 1980 to May 2002 evaluating interventions in patients with COPD. We also hand searched bibliographies of relevant articles and contacted experts in the field.

Study Selection and Data Extraction  We included randomized controlled trials that had follow-up of at least 3 months and contained data on at least 1 of these clinical outcomes: health-related quality of life, exacerbations associated with COPD, or death. For pulmonary rehabilitation, we included studies that had a follow-up of at least 6 weeks. Using standard meta-analytic techniques, the effects of interventions were compared with placebo or with usual care. In secondary analyses, the effects of interventions were compared against each other, where possible.

Data Synthesis  Long-acting ₂-agonists and anticholinergics (tiotropium) reduced exacerbation rates by approximately 20% to 25% (relative risk [RR] for long-acting ₂-agonists, 0.79; 95% CI, 0.69-0.90; RR for tiotropium, 0.74; 95% CI, 0.62-0.89) in patients with moderate to severe COPD. Inhaled corticosteroids also reduced exacerbation rates by a similar amount (RR, 0.76; 95% CI, 0.72-0.80). The beneficial effects were most pronounced in trials enrolling patients with FEV₁ between 1 L and 2 L. Combining a long-acting ₂-agonist with an inhaled corticosteroid resulted in an approximate 30% (RR, 0.70; 95% CI, 0.62-0.78) reduction in exacerbations. Pulmonary rehabilitation improved the health status of patients with moderate to severe disease, but no material effect was observed on long-term survival or hospitalization rates. Domiciliary oxygen therapy improved survival by approximately 40% in patients with PaO₂ lower than 60 mm Hg, but not in those without hypoxia at rest. The data on disease management programs were heterogeneous, but overall no effect was observed on survival or risk of hospitalization. Noninvasive mechanical ventilation was not associated with improved outcomes.

Conclusions  A significant body of evidence supports the use of long-acting bronchodilators and inhaled corticosteroids in reducing exacerbations in patients with moderate to severe COPD. Domiciliary oxygen therapy is the only intervention that has been demonstrated to prolong survival, but only in patients with resting hypoxia.

Author Affiliations: Divisions of Pulmonary Medicine (Drs Sin and Man) and General Medicine (Dr McAlister), University of Alberta, Edmonton; Institute of Health Economics, Edmonton, Alberta (Drs Sin and McAlister); and Department of Medicine, University of Manitoba, Winnipeg (Dr Anthonisen).

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