Reduced COPD Exacerbation Risk Correlates With Improved FEV₁: A Meta-Regression Analysis.

Abstract

The mechanism by which various classes of medication reduce COPD exacerbation risk remains unknown. We hypothesized a correlation between reduced exacerbation risk and improvement in airway patency as measured according to FEV₁. By systematic review, COPD trials were identified that reported therapeutic changes in predose FEV₁ (dFEV₁) and occurrence of moderate to severe exacerbations. Using meta-regression analysis, a model was generated with dFEV₁ as the moderator variable and the absolute difference in exacerbation rate (RD), ratio of exacerbation rates (RRs), or hazard ratio (HR) as dependent variables. The analysis of RD and RR included 119,227 patients, and the HR analysis included 73,475 patients. For every 100-mL change in predose FEV₁, the HR decreased by 21% (95% CI, 17-26; P < .001; R² = 0.85) and the absolute exacerbation rate decreased by 0.06 per patient per year (95% CI, 0.02-0.11; P = .009; R² = 0.05), which corresponded to an RR of 0.86 (95% CI, 0.81-0.91; P < .001; R² = 0.20). The relationship with exacerbation risk remained statistically significant across multiple subgroup analyses. A significant correlation between increased FEV₁ and lower COPD exacerbation risk suggests that airway patency is an important mechanism responsible for this effect.