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Nebulized Corticosteroids in the Treatment of COPD Exacerbations: Systematic Review, Meta-Analysis, and Clinical
Roy A Pleasants1, Tiansheng Wang2, Xiaohan Xu3
1Duke Clinical Research Institute, Durham, NC Pulmonary Department, and Durham VA Medical Center, Durham, North Carolina. roy.pleasants@va.gov.
Background:
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.
Objectives:
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.
Methods:
The primary outcome was a change in FEV1 baseline versus the last measured value. Secondary outcomes were a change in (PaO ) and (PaCO ) baselines versus the last measured values; FEV1, PaO , and PaCO at 24 or 72 h; and hyperglycemia.
Results:
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 PaCO (mean difference of -1.14, 95% CI -2.56 to 0.27, P = .11) but of inferior efficacy for PaO 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).
Conclusions:
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.
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