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
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.
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.
Long-acting β2-agonists and anticholinergics (tiotropium)
reduced exacerbation rates by approximately 20% to 25% (relative risk [RR]
for long-acting β2-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 β2-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.
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.