Emerging pharmaceutical therapies for COPD.
Emerging pharmaceutical therapies for COPD.
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DOI：
10.2147/copd.s121416
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发表时间：
2017
影响因子：
2.8
通讯作者：
Reddy RC
中科院分区：
文献类型：
--
作者：
Lakshmi SP;Reddy AT;Reddy RC
吸烟是慢性阻塞性肺病的主要危险因素，它仍然是世界范围内的负担。目前的治疗只能提供有限的短期效益，并不能阻止病情的发展。目前正在研究多种潜在的治疗靶点，包括copd相关的促炎介质和信号通路。其他正在研究的化合物针对COPD的特定方面或并发症，如粘液分泌过多和肺动脉高压。尽管许多候选疗法没有显示出显著效果，但其他新兴疗法改善了肺功能、肺动脉高压、糖皮质激素敏感性和/或恶化频率。其中包括抑制CXCR2受体、丝裂原活化蛋白激酶/Src激酶、肉豆蔻酰基化富含丙氨酸的C激酶底物、选择素和内皮素受体的化合物。某些转录因子的激活也可能与此相关，因为一项针对COPD合并糖尿病患者的大型回顾性队列研究发现，过氧化物酶体增殖物激活受体γ (PPARγ)激动剂罗格列酮和吡格列酮与降低COPD加重率相关。值得注意的是，一些治疗方法仅在COPD患者可识别的亚组中显示出疗效，这表明亚组识别在未来的治疗策略中可能变得更加重要。这篇综述总结了新兴的COPD治疗药物的现状，并强调了那些最有希望的药物。
COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising.