Disease phenotyping in chronic obstructive pulmonary disease: the neutrophilic endotype.
Disease phenotyping in chronic obstructive pulmonary disease: the neutrophilic endotype.
复制标题
DOI：
10.1097/mcp.0000000000000238
复制
发表时间：
2016-03
影响因子：
3.3
通讯作者：
Blalock JE
中科院分区：
文献类型：
--
作者：
Russell DW;Wells JM;Blalock JE
尽管数十年的科学关注，慢性阻塞性肺疾病（COPD）仍然是世界范围内发病率和死亡率的主要原因，有效的药物种类非常少。这可能部分是因为COPD实际上是一种由具有不同病理生理学（内型）的不同疾病组成的综合征，并且尚未设计治疗以靶向特定于内型的因果病理过程。最近的工作已经开始澄清这些内型的性质和特点。一个有前途的领域集中于中性粒细胞和三肽基质因子脯氨酸-甘氨酸-脯氨酸（PGP）在COPD患者亚组中的中心作用。两种具有COPD治疗竞技场新作用机制的药物（阿奇霉素和罗氟司特）已被证明可减少COPD急性加重。有趣的是，最近的证据表明，这两种药物与PGP/中性粒细胞途径的调节有关，与这种加重减少一致，表明嗜中性粒细胞内型存在并适合药理学靶向。表征COPD内型的进一步工作，包括这种嗜酸性内型，将是重要的，因为我们努力了解这种疾病的机制根源，希望创造更有效的治疗方法。
Despite decades of scientific attention, chronic obstructive pulmonary disease (COPD) remains a major cause of both morbidity and mortality worldwide with strikingly few effective drug classes available. This may be in part because COPD is actually a syndrome composed of distinct diseases with varying pathophysiology (endotypes), and therapies have not been designed to target the causal pathological processes specific to an endotype. Recent work has begun to clarify the nature of these endotypes and characterize them. One promising field focuses on the central role of the neutrophil and the tripeptide matrikine proline-glycine-proline (PGP) in a subset of COPD patients. Two drugs with mechanisms of action novel to the COPD therapeutic arena (azithromycin and roflumilast) have been shown to reduce acute exacerbations of COPD. Intriguingly, recent evidence has linked both of these agents to modulation of the PGP/neutrophil pathway in concert with this exacerbation reduction, suggesting that a neutrophilic endotype is present and amenable to pharmacological targeting. Further work characterizing COPD endotypes, including this neutrophilic endotype, will be important as we strive to understand the mechanistic roots of this disease in the hope of creating more effective therapies.