Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease.
Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease.
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DOI：
10.1016/j.trsl.2015.08.004
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Adcock IM
中科院分区：
文献类型：
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作者：
Durham AL;Caramori G;Chung KF;Adcock IM
哮喘和慢性阻塞性肺疾病(COPD)是慢性呼吸道炎症性疾病，尽管不同疾病炎症的驱动因素和部位不同。嗜中性气道炎的哮喘患者对皮质类固醇的反应较差，而嗜酸性炎症的哮喘患者对皮质类固醇的反应较好。针对Th2-嗜酸性粒细胞网络的生物制剂，如抗IL-4、抗IL-5和抗IL-13，总体上对哮喘无效，但如果使用细胞(如嗜酸性粒细胞)或分子(如Periostin)生物标记物来选择患者，则更有效。这突出了单个炎症介质在驱动炎症反应和准确的疾病表型以允许更好地了解疾病和开发以患者为导向的抗哮喘疗法方面的关键作用。与哮喘患者相比，皮质类固醇对COPD患者的疗效相对较差。尽管COPD患者有分层，但靶向治疗的结果被证明是令人失望的，除了最近使用CXC趋化因子受体(CXCR)2拮抗剂的研究。目前，其他几种新型介体靶向药物正在进行临床试验。与哮喘一样，特定的靶向治疗对特定的COPD患者内型可能是最有益的。在选定的哮喘或COPD患者中使用新型炎症介质靶向治疗药物，以及检测应答或无应答的标志物，将使临床表型和病理生理机制之间的联系得以描述，达到内分型患者的目标。
Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti–interleukin (IL)-4, anti–IL-5, and anti–IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers. This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies. In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients. Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists. Currently, several other novel mediator-targeted drugs are undergoing clinical trials. As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes. The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients.