Nebulized Corticosteroids in the Treatment of COPD Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective.

Abstract

COPD guidelines report that systemic corticosteroids are preferred over inhaled corticosteroids in the treatment of exacerbations, but the inhaled route is considered to be an option. To conduct a systematic review and meta-analysis regarding the efficacy and safety of inhaled corticosteroids for COPD exacerbations. The second objective was to provide pharmacologic and clinical perspectives of inhaled corticosteroids for COPD exacerbations. The primary outcome was a change in FEV1 baseline versus the last measured value. Secondary outcomes were a change in (PaO2 ) and (PaCO2 ) baselines versus the last measured values; FEV1, PaO2 , and PaCO2 at 24 or 72 h; and hyperglycemia. Each of the 9 studies included in the meta-analysis was conducted in subjects who were hospitalized and not critically ill. Our meta-analysis indicated that high-dose nebulized budesonide 4-8 mg/d was noninferior to systemic corticosteroids on the change in FEV1 between baseline and the last measured value (mean difference of 0.05, 95% CI -0.01 to 0.12, P = .13) and PaCO2 (mean difference of -1.14, 95% CI -2.56 to 0.27, P = .11) but of inferior efficacy for PaO2 changes (mean difference of -1.46, 95% -2.75 to -0.16, P = .03). Hyperglycemia was less frequent with high-dose nebulized budesonide (risk ratio, 0.13; 95% CI 0.03-0.46; P = .002). Based on our meta-analysis with a change in FEV1 as the primary end point, high-dose nebulized budesonide was an acceptable alternative to systemic corticosteroids in hospitalized subjects with COPD exacerbations who were not critically ill. Additional well-designed prospective studies are needed in both the acute care and ambulatory settings. We provide perspective on how this evidence might be applied in clinical practice.