Chronic obstructive pulmonary disease (
COPD) is an under-recognized cause of morbidity and mortality worldwide that imposes an ever increasing burden on the patient and society alike. The disease encompasses multiple structural and functional components of which
inflammation is at the core of the disease, affecting the lungs and other organs. Consequently, current treatment strategies are aimed at treating both the symptoms and the
pulmonary inflammation underlying the complex pathophysiology of
COPD. Smoking cessation is the only intervention currently shown to slow
disease progression in
COPD and decrease all-cause mortality, aside from lung transplant,
lung-volume reduction surgery and
oxygen therapy in selective patients. However, this intervention is difficult to achieve and sustain because of the addictive and chronic relapsing nature of cigarette smoking.
Pharmacotherapy with bronchodilating agents, including the beta 2-agonists,
anticholinergics and methylxanthines, is central to the symptomatic management of all stages of
COPD. While inhaled
corticosteroids (ICS) are employed to reduce
inflammation in more severe patients, their role as stand alone medication in
COPD is not well defined. However, increasing evidence suggests that long-acting beta 2-agonists (LABAs) and ICS have complementary and synergistic effects, when delivered as combination
therapy from a single
inhaler. In this respect, two preparations comprising combinations of salmeterol+fluticasone
propionate (SFC) and formoterol+budesonide (FBC) are currently available and employed for treatment of more severe disease. Several large-scale studies in patients with moderate-to-severe
COPD have demonstrated that treatment with SFC and FBC leads to significantly greater improvements in lung function, exacerbations, health status and
breathlessness, compared with placebo or monotherapy with the component drugs. In the recently published landmark study, Towards a Revolution in
COPD Health (TORCH), regular treatment with SFC narrowly missed demonstrating a statistically significant benefit on the reduction in all-cause mortality over 3 years (17.5% reduction in risk, P=0.052), further emphasizing the clinical usefulness of LABA+ICS
therapy in
COPD. In view of this increasing evidence for the additional effectiveness of LABA+ICS combinations compared with the individual components, and the potential benefits of LABA+ICS on lung function,
disease progression and potentially on all-cause mortality, initiation of LABA+ICS combination treatment early in the
COPD disease process may be warranted.
SEARCH STRATEGY: The studies discussed in this review were identified from systematic searches of Medline and the Cochrane Database, up to October 2007, for articles in English or with English abstracts describing randomized, double-blind, parallel-group/crossover trials of at least 24 weeks' duration. All searches were performed using the terms:
chronic obstructive pulmonary disease,
COPD,
chronic obstructive airway disease, or
COAD AND either
salmeterol,
formoterol, long-acting beta 2-adrenoceptor agonist,
fluticasone propionate,
budesonide, inhaled
corticosteroids, or inhaled glucocorticosteroids. Additional relevant references were identified from the reference lists of selected papers. Only studies that compared a combined LABA+ICS
therapy with its monotherapy components were selected for inclusion in this manuscript.