Does roflumilast improve dyspnea in patients with chronic obstructive pulmonary disease? A meta-analysis

Introduction: Although several large studies showed roflumilast (Rof) has demonstrated efficacy in patients with chronic obstructive pulmonary disease (COPD), the efficacy of Rof in dyspnea remains unclear. We therefore undertook a meta-analysis to assess the efficacy of Rof in dyspnea for COPD patients. Methods: A computerized search through electronic databases was performed to obtain randomized controlled trials (RCTs). Dyspnea was assessed by the transition dyspnea index (TDI) and the UCSD Shortness of Breath Questionnaire (SOBQ). The quality of the included studies was assessed by the Jadad score. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I-2 test. The effect sizes were compared with the minimum clinically important difference (MCID). Results: Four RCTs involving 4,767 patients with forced expiratory volume in one second (FEV1) <80% predicted met the inclusion criteria. The Jadad score of each study was 5 scores. Rof statistically improved the TDI focal score (WMD =0.30 units; 95% CI: 0.14-0.46), but failed to decrease the SOBQ (WMD =-1.10 units; 95% CI: -4.24 to 2.04). The overall effect sizes were lower than the MCID of the TDI and the SOBQ, respectively. Conclusions: Sufficient evidence to support Rof relieving dyspnea in COPD patients is currently lacking. Further studies are needed to investigate the effects of Rof in dyspnea, especially for COPD patients with a different phenotype.