Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis.
BACKGROUND
Recent studies of inhaled corticosteroid (ICS) therapy for managing stable chronic obstructive pulmonary disease (COPD) have yielded conflicting results regarding survival and risk of adverse events.


OBJECTIVE
To systematically review and quantitatively synthesize the effects of ICS therapy on mortality and adverse events in patients with stable COPD.


METHODS
Search of MEDLINE, CENTRAL, EMBASE, CINAHL, Web of Science, and PsychInfo through February 9, 2008.


METHODS
Eligible studies were double-blind, randomized controlled trials comparing ICS therapy for 6 or more months with nonsteroid inhaled therapy in patients with COPD.


METHODS
Two authors independently abstracted data including study characteristics, all-cause mortality, pneumonia, and bone fractures. The I(2) statistic was used to assess heterogeneity. Study-level data were pooled using a random-effects model (when I(2) > or = 50%) or a fixed-effects model (when I(2) < 50%). For the primary outcome of all-cause mortality at 1 year, our meta-analysis was powered to detect a 1.0% absolute difference in mortality, assuming a 2-sided alpha of .05 and power of 0.80.


RESULTS
Eleven eligible randomized controlled trials (14,426 participants) were included. In trials with mortality data, no difference was observed in 1-year all-cause mortality (128 deaths among 4636 patients in the treatment group and 148 deaths among 4597 patients in the control group; relative risk [RR], 0.86; 95% confidence interval [CI], 0.68-1.09; P = .20; I(2) = 0%). In the trials with data on pneumonia, ICS therapy was associated with a significantly higher incidence of pneumonia (777 cases among 5405 patients in the treatment group and 561 cases among 5371 patients in the control group; RR, 1.34; 95% CI, 1.03-1.75; P = .03; I(2) = 72%). Subgroup analyses indicated an increased risk of pneumonia in the following subgroups: highest ICS dose (RR, 1.46; 95% CI, 1.10-1.92; P = .008; I(2) = 78%), shorter duration of ICS use (RR, 2.12; 95% CI, 1.47-3.05; P < .001; I(2) = 0%), lowest baseline forced expiratory volume in the first second of expiration (RR, 1.90; 95% CI, 1.26-2.85; P = .002; I(2) = 0%), and combined ICS and bronchodilator therapy (RR, 1.57; 95% CI, 1.35-1.82; P < .001; I(2) = 24%).


CONCLUSIONS
Among patients with COPD, ICS therapy does not affect 1-year all-cause mortality. ICS therapy is associated with a higher risk of pneumonia. Future studies should determine whether specific subsets of patients with COPD benefit from ICS therapy.
Drummond
M Bradley
MB
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Dasenbrook
Elliott C
EC
Pitz
Marshall W
MW
Murphy
David J
DJ
Fan
Eddy
E
D000280:Administration, Inhalation; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000453:epidemiology; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009026:Mortality; D011014:Pneumonia / Q000453:epidemiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids