Chalmers James D, Metersky Mark, Aliberti Stefano, Morgan Lucy, Fucile Sebastian, Lauterio Melanie, McDonald Patrick P
Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK.
University of Connecticut School of Medicine, Farmington, CT, USA.
Eur Respir Rev. 2025 Apr 2;34(176). doi: 10.1183/16000617.0179-2024. Print 2025 Apr.
Noncystic fibrosis bronchiectasis, hereafter referred to as bronchiectasis, is a chronic, progressive lung disease that can affect people of all ages. Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life. The pathophysiology of bronchiectasis has been described as a vicious vortex of chronic inflammation, recurring airway infection, impaired mucociliary clearance and progressive lung damage that promotes the development and progression of the disease. This review describes the pivotal role of neutrophil-driven inflammation in the pathogenesis and progression of bronchiectasis. Delayed neutrophil apoptosis and increased necrosis enhance dysregulated inflammation in bronchiectasis and failure to resolve this contributes to chronic, sustained inflammation. The excessive release of neutrophil serine proteases, such as neutrophil elastase, cathepsin G and proteinase 3, promotes a protease-antiprotease imbalance that correlates with increased inflammation in bronchiectasis and contributes to disease progression. While there are currently no licensed therapies to treat bronchiectasis, this review will explore the evolving evidence for neutrophilic inflammation as a novel treatment target with meaningful clinical benefits.
非囊性纤维化支气管扩张症（以下简称支气管扩张症）是一种可影响各年龄段人群的慢性进行性肺部疾病。具有临床意义的支气管扩张症患者会出现慢性咳嗽、咳痰，以及反复呼吸道感染、疲劳和健康相关生活质量受损。支气管扩张症的病理生理学被描述为慢性炎症、反复气道感染、黏液纤毛清除功能受损和进行性肺损伤的恶性循环，这促进了该疾病的发生和发展。本综述描述了中性粒细胞驱动的炎症在支气管扩张症发病机制和进展中的关键作用。中性粒细胞凋亡延迟和坏死增加会加剧支气管扩张症中失调的炎症，而未能解决这一问题会导致慢性持续性炎症。中性粒细胞丝氨酸蛋白酶（如中性粒细胞弹性蛋白酶、组织蛋白酶G和蛋白酶3）的过度释放会导致蛋白酶-抗蛋白酶失衡，这与支气管扩张症中炎症增加相关，并促进疾病进展。虽然目前尚无获批用于治疗支气管扩张症的疗法，但本综述将探讨嗜中性粒细胞炎症作为具有显著临床益处的新型治疗靶点的不断发展的证据。
