Lakshmi Sowmya P, Reddy Aravind T, Reddy Raju C
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine.
Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
Int J Chron Obstruct Pulmon Dis. 2017 Jul 21;12:2141-2156. doi: 10.2147/COPD.S121416. eCollection 2017.
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.
慢性阻塞性肺疾病（COPD）是一种全球性负担，吸烟是其主要危险因素。目前的治疗方法仅能提供有限的短期益处，无法阻止疾病进展。目前正在研究多种潜在的治疗靶点，包括与COPD相关的促炎介质和信号通路。其他研究性化合物则针对COPD的特定方面或并发症，如黏液高分泌和肺动脉高压。尽管许多候选疗法未显示出显著效果，但其他新兴疗法已改善了肺功能、肺动脉高压、糖皮质激素敏感性和/或急性加重频率。其中包括抑制CXCR2受体、丝裂原活化蛋白激酶/Src激酶、富含丙氨酸的豆蔻酰化蛋白激酶底物、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急性加重率相关。值得注意的是，几种疗法仅在可识别的COPD患者亚组中显示出疗效，这表明亚组识别在未来治疗策略中可能变得更加重要。本综述总结了COPD新兴治疗药物的现状，并重点介绍了那些最有前景的药物。
