title: Can roflumilast, a phosphodiesterase-4 inhibitor, improve clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease? A meta-analysis.
abstract: BACKGROUND
  Effects of roflumilast on lung function, symptoms, acute exacerbation and adverse events in patients with chronic obstructive pulmonary disease (COPD) are controversial. We aimed to further clarify the efficacy and safety of roflumilast in treatment of moderate-to-severe COPD.
  
  
  METHODS
  From 1946 to November 2015, we searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials, ISI Web of Science and American College of Physician using "roflumilast" and "chronic obstructive pulmonary disease" or "COPD". Randomized controlled trials that reported forced expiratory volume in one second (FEV1), forced vital capacity (FVC), transition dyspnea index (TDI), St George's Respiratory Questionnaire (SGRQ), and incidence of COPD exacerbations and adverse events were eligible. We conducted the heterogeneities test and sensitivity analysis, and random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively. Cochrane systematic review software, Review Manager (RevMan), was used to test the hypothesis by Mann-Whitney U-test.
  
  
  RESULTS
  Thirteen trials with a total of 14,563 patients were pooled in our final studies. Except for SGRQ (I (2) = 63 %, χ (2) = 1.71, P = 0.07) and adverse events (I (2) = 94 %, χ (2) = 0.03, P < 0.001), we did not find statistical heterogeneity in outcome measures. The pooled MD of pre- and post-bronchodilator FEV1 was 54.60 (95 % confidence interval (CI) 46.02 ~ 63.18) and 57.86 (95 % CI 49.80 ~ 65.91), and both showed significant improvement in patients with roflumilast (z = 12.47, P <0.001; z = 14.07, P < 0.001), so did in FVC (MD 90.37, 95 % CI 73.95 ~ 106.78, z = 10.79, P < 0.001). Significant alleviation of TDI (MD 0.30, 95 % CI 0.14 ~ 0.46, z = 3.67, P < 0.001) and decrease of acute exacerbation (RR 0.86, 95 % CI 0.81 ~ 0.91, z = 5.54, P < 0.001) were also identified in treatment of roflumilast, but without significant difference in SGRQ (MD -1.30, 95 % CI -3.16 ~ 0.56, z = 1.37, P = 0.17). Moreover, roflumilast significantly increased the incidence of adverse events compared with placebo (RR 1.31, 95 % CI 1.16 ~ 1.47, z = 4.32, P < 0.001).
  
  
  CONCLUSIONS
  Roflumilast can be considered as an alternative therapy in selective patients with moderate-to-severe COPD.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Sichuan University, Chengdu, China. kevinluo0708@yahoo.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Sichuan University, Chengdu, China. wangk0909@yahoo.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, West China School of Medicine and West China Hospital, Sichuan University, Chengdu, China. danielleliu0802@yahoo.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Sichuan University, Chengdu, China. liangbinmiao@163.com.|, No. 37 Guoxue Alley, Chengdu, 610041, China. liangbinmiao@163.com.
authors.forename: Bin-Miao
authors.initials: BM
authors.lastname: Liang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Sichuan University, Chengdu, China. liuct0910@yahoo.com.|, No. 37 Guoxue Alley, Chengdu, 610041, China. liuct0910@yahoo.com.
authors.forename: Chun-Tao
authors.initials: CT
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000631:Aminopyridines / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D003521:Cyclopropanes / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D012129:Respiratory Function Tests / Q000706:statistics & numerical data*; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast