Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis.
Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis.
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DOI：
10.3389/fphar.2020.576293
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发表时间：
2020
影响因子：
5.6
通讯作者：
Ratjen F
中科院分区：
文献类型：
--
作者：
Perrem L;Ratjen F
在大多数患者中，CF气道的炎症反应开始于疾病过程的早期，并在一生中持续存在。炎症，主要是中性粒细胞，加重了呼吸道阻塞，在结构性肺损伤的发展中起着关键作用。尽管囊性纤维化跨膜调节因子可能会在未来几年对慢性肺疾病的发展轨迹产生巨大影响，但解决肺部疾病的其他重要方面，如炎症，仍将是优先事项。考虑到中性粒细胞及其产物在炎症反应中的核心作用，潜在的治疗方法最终应该会影响中性粒细胞及其产物。理想的抗炎治疗将在炎症级联的促炎和促消退臂上发挥双重作用，这两者都会导致CF中炎症的失调。该综述概述了在临床试验设计中需要考虑的关键因素，以评估CF的抗炎治疗。从这一领域以前的临床试验中已经学到了重要的教训，选择正确的疗效终点是任何抗炎药物开发计划成功的关键。识别和验证能够监测疾病活动和治疗反应的非侵入性生物标志物、新的成像技术和敏感的肺功能测试是重要的研究领域，将有助于未来抗炎药物试验的设计。
The inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibrosis transmembrane regulator modulators will likely have a dramatic impact on the trajectory of CF lung disease over the coming years, addressing other important aspects of lung disease such as inflammation will nevertheless remain a priority. Considering the central role of neutrophils and their products in the inflammatory response, potential therapies should ultimately affect neutrophils and their products. The ideal anti-inflammatory therapy would exert a dual effect on the pro-inflammatory and pro-resolution arms of the inflammatory cascade, both of which contribute to dysregulated inflammation in CF. This review outlines the key factors to be considered in the design of clinical trials evaluating anti-inflammatory therapies in CF. Important lessons have been learned from previous clinical trials in this area and choosing the right efficacy endpoints is key to the success of any anti-inflammatory drug development program. Identifying and validating non-invasive biomarkers, novel imaging techniques and sensitive lung function tests capable of monitoring disease activity and therapeutic response are important areas of research and will be useful for the design of future anti-inflammatory drug trials.
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影响因子：
10
作者：
Amin, Reshma;Subbarao, Padmaja;Ratjen, Felix
通讯作者：
Ratjen, Felix
影响因子：
2.2
作者：
Elborn, J. Stuart;Ahuja, Sanjeev;Rowe, Steven M.
通讯作者：
Rowe, Steven M.
DOI：
10.1111/cts.12426
发表时间：
2017-01
期刊：
Clinical and translational science
影响因子：
--
作者：
Elborn JS;Bhatt L;Grosswald R;Ahuja S;Springman EB
通讯作者：
Springman EB
影响因子：
10
作者：
Block, J. K.;Vandemheen, K. L.;Aaron, S. D.
通讯作者：
Aaron, S. D.
DOI：
10.1164/ajrccm.150.1.7912987
发表时间：
1994-07-01
影响因子：
24.7
作者：
BIRRER, P;MCELVANEY, NG;CRYSTAL, RG
通讯作者：
CRYSTAL, RG