Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Cystic Fibrosis Unit, Beaumont Hospital, Dublin, Ireland.
Thorax. 2023 Aug;78(8):835-839. doi: 10.1136/thorax-2022-219943. Epub 2023 May 19.
Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to improve lung function in people with cystic fibrosis (PWCF). However, its biological effects remain incompletely understood. Here we describe alterations in pulmonary and systemic inflammation in PWCF following initiation of ETI. To address this, we collected spontaneously expectorated sputum and matching plasma from PWCF (n=30) immediately prior to ETI therapy, then again at 3 and 12 months. Within 3 months, PWCF demonstrated reduced activity of neutrophil elastase, proteinase three and cathepsin G, and decreased concentrations of interleukin (IL)-1β and IL-8 in sputum, accompanied by decreased burden and restoration of secretory leukoprotease inhibitor levels. Once treated with ETI, all airway inflammatory markers studied in PWCF had reduced to levels found in matched non-CF bronchiectasis controls. In PWCF with advanced disease, ETI resulted in decreased plasma concentrations of IL-6, C-reactive protein and soluble TNF receptor one as well as normalisation of levels of the acute phase protein, alpha-1 antitrypsin. These data clarify the immunomodulatory effects of ETI and underscore its role as a disease modifier.
依利卓（elexacaftor/tezacaftor/ivacaftor）治疗已被证明可改善囊性纤维化患者（PWCF）的肺功能。然而，其生物学效应仍不完全清楚。本研究描述了 PWCF 开始依利卓治疗后肺部和全身炎症的变化。为了解决这个问题，我们收集了 PWCF（n=30）在开始依利卓治疗前、治疗后 3 个月和 12 个月时的自然咳出的痰和匹配的血浆。在 3 个月内，PWCF 表现出中性粒细胞弹性蛋白酶、蛋白酶 3 和组织蛋白酶 G 活性降低，痰中白细胞介素（IL）-1β和 IL-8 浓度降低，同时负担减轻和分泌型白细胞蛋白酶抑制剂水平恢复。一旦接受依利卓治疗，PWCF 中所有研究的气道炎症标志物均降低至与匹配的非 CF 支气管扩张症对照组相同的水平。在疾病进展的 PWCF 中，依利卓治疗导致血浆中 IL-6、C 反应蛋白和可溶性 TNF 受体一的浓度降低，急性相蛋白α-1 抗胰蛋白酶的水平正常化。这些数据阐明了依利卓的免疫调节作用，并强调了其作为疾病修饰剂的作用。
