Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis

JAMA. 2008 Nov 26;300(20):2407-16. doi: 10.1001/jama.2008.717.

Abstract

Context: 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.

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

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

Data extraction: 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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Fractures, Bone / epidemiology
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • Mortality
  • Pneumonia / epidemiology
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Randomized Controlled Trials as Topic
  • Risk

Substances

  • Anti-Inflammatory Agents
  • Glucocorticoids