| Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the airway. None of the existing medications for COPD has been shown to modify the long-term decline in lung function. It has been shown that the phosphodiesterase-4 (PDE4) inhibitors, which could inhibit the main inflammatory cells of COPD such as neutrophil, airway macrophages, CD8+ T lymphocytes and airway epithelial celles, is of broad-spectrum anti-inflammatory effects in patients with COPD. Cilomilast is a selective PDE4 inhibitor currently under development for the treatment of COPD and asthma. The aim of this study was to estimate the efficacy and safety of cilomilast in patients with COPD who would receive 24 weeks treatment. Furthermore, we aimed to investigate the anti-inflammatory action of cilomilast by performing differential cell counts in induced sputum and examining markers of inflammation in induced sputum and plasma. MethodsA randomized, double-blind, placebo-controlled trial was performed in patients with COPD who were all in the stable stage. After 4 weeks run-in period, 38 patients with clinically stable COPD were divided randomly into treatment group or control group. The treatment group was treated with Cilomilast 15mg twice a day and the control group placebo twice a day. The therapeutic course of both groups was 24 weeks. The changes of lung function, the evaluation of COPD exacerbations, SGRQ scores, dyspnea scores, cough scores, sputum scores, life-sign, ECG, blood analysis, urine analysis, blood biochemical test and ratio of adverse effects were observed between two groups. At the start and end of the treatment period differential cell counts in induced sputum were observed and the levels of IL-8 and TNF-α were measured in sputum supernatant and plasma using specific sandwich enzyme-linked immunosorbent assay (ELISA). Results1. Changes in the clinical symptom At the end of the treatment period, significant reduction was observed in mild to moderate exacerbations versus control group(P<0.001 and 0.01, respectively). Compared with the baseline, significant improvement was observed in dyspnea after 16 and 24weeks(P<0.001) and in cough after 16 and 24weeks(P<0.05 and 0.01, respectively) and in sputum symptoms after 8, 16 and 24weeks(P<0.05, 0.01 and 0.001, respectively) in the treatment group. Whereas, no significant improvement in dyspnea, cough and sputum symptoms versus baseline in the control group.2. Changes in lung function(1) FEV1 and FEV1%pred No significant change in FEV1 and FEV1% predicted was observed in the treatment group in the whole treatment period. Compared with the baseline, significant decrease in FEV1 was observed in the control group after 20 and 24 weeks of treatment (P<0.05 and 0.01, respectively) and significant decrease in FEV1% predicted at 24 weeks (P<0.01).(2) FVC and FVC%pred At the end of the treatment period, significant improvement of FVC and FVC% predicted was found in the treatment group (P<0.05 and 0.01, respectively), but no significant change in FVC and FVC% predicted versus baseline in the control group in the whole treatment period. (3) FEV1/FVC No significant change in FEV1/FVC was observed in the treatment group in the whole treatment period. Compared with the baseline, significant decrease in FEV1/FVC was observed in the control group at 20 and 24 weeks after treatment (P<0.05 and 0.01, respectively). (4) PEF Compared with the baseline, no significant change in PEF was found in two groups in the whole treatment period.(5) MMEF In the whole treatment period, no significant change in MMEF was observed in the treatment group. Compared with the baseline, significant decrease in MMEF was observed in the control group at 24 weeks after treatment (P<0.01). MMEF could be maintained in the treatment group. (6) TLC and TLC%pred At the end of the treatment period, significant improvement of TLC and TLC% predicted was found in the treatment group (P<0.05), but no significant change in TLC and TLC% predicted versus baseline in the control group in the... |
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