急性呼吸窘迫综合征
医学
中性粒细胞弹性蛋白酶
临床试验
弹性蛋白酶
急性呼吸窘迫
弥漫性肺泡损伤
不利影响
重症监护医学
免疫学
药理学
肺
炎症
内科学
化学
酶
生物化学
作者
Maria Gabriella Matera,Paola Rogliani,Josuel Ora,Luigino Calzetta,Mario Cazzola
标识
DOI:10.1080/13543784.2023.2263366
摘要
Excessive activity of neutrophil elastase (NE), the main enzyme present in azurophil granules in the neutrophil cytoplasm, may cause tissue injury and remodeling in various lung diseases, including acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), in which it is crucial to the immune response and inflammatory process. Consequently, NE is a possible target for therapeutic intervention in ALI/ARDS.The protective effects of several NE inhibitors in attenuating ALI/ARDS in several models of lung injury are described. Some of these NE inhibitors are currently in clinical development, but only sivelestat has been evaluated as a treatment for ALI/ARDS.Preclinical research has produced encouraging information about using NE inhibitors. Nevertheless, only sivelestat has been approved for this clinical indication, and only in Japan and South Korea because of the conflicting results of clinical trials and likely also because of the potential adverse events. Identifying subsets of patients with ARDS most likely to benefit from NE inhibitor treatment, such as the hyperinflammatory phenotype, and using a more advanced generation of NE inhibitors than sivelestat could enable better clinical results than those obtained with elastase inhibitors.
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