Polverino Eva, Rosales-Mayor Edmundo, Dale Glenn E, Dembowsky Klaus, Torres Antoni
Institut Clínic Respiratori, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Ciber de Enfermedades Respiratorias, Barcelona, Spain.
Drug Discovery and Development, Polyphor Ltd., Allschwil, Switzerland.
Chest. 2017 Aug;152(2):249-262. doi: 10.1016/j.chest.2017.03.056. Epub 2017 Apr 23.
In many respiratory diseases characterized by an intense inflammatory response, the balance between proteolytic enzymes (proteases, including elastases) and their inhibitors (proteinases inhibitors) is not neutral. Excess activity of neutrophil elastase (NE) and similar proteases has been reported to cause tissue damage and to alter the remodeling process in many clinical conditions such as pneumonia, respiratory distress, and acute lung injury (ALI). Several experimental NE inhibitors have been tested in preclinical and clinical studies of different conditions of inflammatory lung injury such as ALI and pneumonia, with contrasting results. This study reviews the literature regarding NE inhibitors in the field of respiratory diseases and reflects on possible future developments. In particular, we highlight potential gaps in the scientific evidence and discuss potential strategies for focusing investigation on antielastases in clinical practice through the selection of targeted populations and proper outcomes.
在许多以强烈炎症反应为特征的呼吸系统疾病中，蛋白水解酶（蛋白酶，包括弹性蛋白酶）与其抑制剂（蛋白酶抑制剂）之间的平衡并非中性。据报道，中性粒细胞弹性蛋白酶（NE）和类似蛋白酶的过度活性会导致组织损伤，并在许多临床病症（如肺炎、呼吸窘迫和急性肺损伤（ALI））中改变重塑过程。几种实验性NE抑制剂已在不同炎症性肺损伤病症（如ALI和肺炎）的临床前和临床研究中进行了测试，结果各异。本研究回顾了呼吸系统疾病领域中关于NE抑制剂的文献，并思考了未来可能的发展。特别是，我们强调了科学证据中的潜在差距，并讨论了通过选择目标人群和合适的结果，在临床实践中聚焦抗弹性蛋白酶研究的潜在策略。
