Targeting neutrophil serine proteases in bronchiectasis.

Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3.

中性粒细胞释放中性粒细胞丝氨酸蛋白酶（NSPs），如中性粒细胞弹性蛋白酶（NE）、组织蛋白酶G和蛋白酶3。

When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur.

当慢性高水平的自由NSP活性超过保护性抗蛋白酶时，可能会发生结构性肺破坏、粘膜相关缺陷、进一步感染易感性增加以及临床结果恶化。

Despite the defined role of prolonged, high levels of NSPs in bronchiectasis, no drug that controls neutrophilic inflammation is licensed for the treatment of bronchiectasis.

尽管已明确长期高水平的NSPs在支气管扩张症中的作用，但目前尚无控制中性粒细胞炎症的药物被批准用于支气管扩张症的治疗。

Previous methods of suppressing neutrophilic inflammation (such as direct inhibition of NE) have not been successful; however, an emerging therapy designed to address neutrophil-mediated pathology, inhibition of the cysteine protease cathepsin C (CatC, also known as dipeptidyl peptidase 1), is a promising approach to ameliorate neutrophilic inflammation, since this may reduce the activity of all NSPs implicated in bronchiectasis pathogenesis, and not just NE.

先前抑制中性粒细胞炎症的方法（如直接抑制NE）并未成功；然而，一种新兴的治疗方法旨在解决中性粒细胞介导的病理，即抑制半胱氨酸蛋白酶组织蛋白酶C（CatC，也称为二肽基肽酶1），这是一种有前景的方法来缓解中性粒细胞炎症，因为这可能减少所有在支气管扩张症发病机制中涉及的NSPs的活性，而不仅仅是NE。

Current data suggest that CatC inhibition may effectively restore the protease-antiprotease balance in bronchiectasis and improve disease outcomes as a result.

当前数据显示，CatC抑制可能有效地恢复支气管扩张症中的蛋白酶-抗蛋白酶平衡，并因此改善疾病结果。

Clinical trials for CatC inhibitors in bronchiectasis have reported positive phase III results.

在支气管扩张症中，CatC抑制剂的临床试验报告了积极的III期结果。

In this narrative review, we discuss the role of high NSP activity in bronchiectasis, and how this feature drives the associated morbidity and mortality seen in bronchiectasis.

在这篇叙述性综述中，我们讨论了高NSP活性在支气管扩张症中的作用，以及这一特征如何推动支气管扩张症中所见的相关发病率和死亡率。

This review discusses therapeutic approaches aimed at treating neutrophilic inflammation in the bronchiectasis lung, summarising clinical trial outcomes and highlighting the need for more treatment strategies that effectively address chronic neutrophilic inflammation in bronchiectasis.

本综述讨论了旨在治疗支气管扩张症患者中性粒细胞性炎症的治疗策略，总结了临床试验结果，并强调了需要更多有效应对支气管扩张症中慢性中性粒细胞性炎症的治疗策略。