Wagner Linda Timm, Kenreigh Charlotte A
MLC Solutions Ltd, Galena, Ohio, USA.
Core Evid. 2005;1(1):23-33. doi: 10.2147/ce.s6404. Epub 2005 Mar 31.
Chronic obstructive pulmonary disease (COPD), characterized by a progressive deterioration of lung function caused primarily by the inhalation of toxic substances, is a leading cause of morbidity and mortality worldwide. Current treatment options for the management of its symptoms include the use of bronchodilators and glucocorticoid agents that are not universally beneficial and which are associated with limitations. Phosphodiesterase-4 (PDE4) inhibitors are a novel class of antiinflammatory agents being developed for COPD treatment.
The purpose of this article is to review the clinical potential of roflumilast, a PDE4 inhibitor currently in phase III clinical trials, in the management of patients with COPD.
Phase II studies indicate that roflumilast can be given orally once daily. Preliminary evidence from two phase III, randomized, double-blind, placebo-controlled studies suggest that roflumilast improves or stabilizes lung function, as measured by forced expiratory volume in 1 s and 6 s (FEV(1) and FEV(6)), forced vital capacity (FVC), and peak expiratory flow (PEF) in patients with COPD. Improvements in COPD exacerbation rate were also reported in these trials. Quality of life, as measured by the St George's Respiratory Questionnaire, also improved with roflumilast treatment. Clinical studies to date suggest that roflumilast is well tolerated.
Current evidence supports the use of roflumilast in the management of COPD as shown by improvements in patients' symptoms and quality of life, and good tolerability profile. Its once-daily oral dosing regimen is unique among current therapies for COPD. This potential and the place of roflumilast in the stepwise management of the disease need to be confirmed as further evidence is published. Additional evidence will also be welcome to determine if its mechanism of action moderates the progression of lung function deterioration.
慢性阻塞性肺疾病（COPD）主要由吸入有毒物质导致肺功能进行性恶化，是全球发病和死亡的主要原因。目前用于管理其症状的治疗选择包括使用支气管扩张剂和糖皮质激素药物，但这些药物并非对所有患者都有益，且存在局限性。磷酸二酯酶 - 4（PDE4）抑制剂是一类正在开发用于治疗COPD的新型抗炎药物。
本文旨在综述目前处于III期临床试验的PDE4抑制剂罗氟司特在COPD患者管理中的临床潜力。
II期研究表明，罗氟司特可以每日口服一次。两项III期随机、双盲、安慰剂对照研究的初步证据表明，罗氟司特可改善或稳定COPD患者的肺功能，通过1秒用力呼气量和6秒用力呼气量（FEV(1)和FEV(6)）、用力肺活量（FVC）以及呼气峰值流速（PEF）来衡量。这些试验还报告了COPD急性加重率的改善情况。使用圣乔治呼吸问卷测量的生活质量在罗氟司特治疗后也有所改善。迄今为止的临床研究表明，罗氟司特耐受性良好。
目前的证据支持使用罗氟司特来管理COPD，这体现在患者症状和生活质量的改善以及良好的耐受性方面。其每日一次的口服给药方案在目前的COPD治疗方法中是独特的。随着更多证据的发表，罗氟司特的这种潜力及其在该疾病逐步管理中的地位需要得到确认。还欢迎更多证据来确定其作用机制是否能减缓肺功能恶化的进程。
