elexaftor /tezacaftor/ivacaftor的全身炎症谱变化预测囊性纤维化的临床结局

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.548

L. Jonckheere , L. Vande Sande , I. Janssens , Y. Vande Weygaerde , S. Van Biervliet , H. Schaballie , P. Schelstraete , T. Maes , C. Bosteels , E. Van Braeckel

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引用次数: 0

摘要

囊性纤维化（CF）以全身性炎症为特征，CFTR调节剂如elexaftor /tezacaftor/ivacaftor （ETI）除了影响临床结果外，还可能影响免疫反应。本研究调查了ETI如何改变全身细胞因子水平，以及这些变化是否能独立预测CF患者的临床结果。方法测定90例pwCF患者在ETI治疗6个月前后血清中8种细胞因子（TNF-α、IL-6、IL-13、IFN-γ、IL-8、IL-17A、IL-10、IL-1β）水平。使用中位数报告细胞因子，使用平均值报告临床结果（ppFEV1，恶化频率）。配对t检验用于分析对数转化的细胞因子水平，并使用多变量回归模型评估细胞因子变化作为临床结果的独立预测因子。结果seti导致TNF-α、IL-6、IL-13、IL-8、IL-17A和IL-1β水平降低(从0.54降至0.45；1.52 ~ 0.61；0.98 ~ 0.69；23.78到13.35。分别为8.74 ~ 3.18和0.11 ~ 0.03 pg/mL；所有术;0.0001)。IFN-γ升高（4.77 ~ 6.03 pg/mL, p= 0.05），而IL-10保持不变（0.42 ~ 0.41 pg/mL, p=0.214）。临床结果得到改善，ppFEV1从80.49%增加到89.79%，恶化频率从1.78次/年下降到0.50次/年（p<均为0.0001）。多因素回归分析表明，IFNy的升高和IL-6的降低预测ppFEV1的升高，而IL-10的升高和IL-1b的降低预测加重频率的降低。调整后的R²值ppFEV1为0.406，加重频率为0.799。结论pwCF治疗ETI时，促炎细胞因子（如IL-6和IL-1β）的显著降低和免疫调节细胞因子（如IL-10和IFN-γ）的显著升高独立预测ppFEV1的改善和更少的恶化。这些发现强调了ETI作为治疗和免疫调节剂的双重作用，支持细胞因子谱分析用于个性化CF护理。

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WS10.03Shifts in systemic inflammatory profiles on elexacaftor/tezacaftor/ivacaftor predict clinical outcomes in cystic fibrosis

Objectives

Cystic fibrosis (CF) is characterised by systemic inflammation, and CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) may influence immune responses in addition to clinical outcomes. This study investigated how ETI alters systemic cytokine levels and whether these changes independently predict clinical outcomes in people living with CF (pwCF).

Methods

Serum levels of eight cytokines (TNF-α, IL-6, IL-13, IFN-γ, IL-8, IL-17A, IL-10, and IL-1β) were measured in 90 pwCF before and after six months on ETI. Cytokines were reported using medians, and clinical outcomes (ppFEV₁, exacerbation frequency) using means. Paired t-tests were used to analyse log-transformed cytokine levels, and multivariate regression models to assess cytokine changes as independent predictors of clinical outcomes.

Results

ETI led to reductions in TNF-α, IL-6, IL-13, IL-8, IL-17A and IL-1β (from 0.54 to 0.45; 1.52 to 0.61; 0.98 to 0.69; 23.78 to 13.35. 8.74 to 3.18 and 0.11 to 0.03 pg/mL respectively; all p<0.0001). IFN-γ increased (4.77 to 6.03 pg/mL, p<0.05), while IL-10 remained unchanged (0.42 to 0.41 pg/mL, p=0.214). Clinical outcomes improved, with ppFEV₁ increasing from 80.49% to 89.79% and exacerbation frequency dropping from 1.78 to 0.50 episodes/year (both p<0.0001). Multivariate regression analysis demonstrated that increase in IFNy and decrease in IL-6 predicted ppFEV1 increase, whereas increase in IL-10 and decrease in IL-1b predicted reductions in exacerbation frequency. Adjusted R² values were 0.406 for ppFEV₁ and 0.799 for exacerbation frequency.

Conclusion

In pwCF on ETI, greater reductions in pro-inflammatory cytokines (e.g. IL-6 and IL-1β) and larger increases in immunomodulatory cytokines (e.g. IL-10 and IFN-γ) independently predict better ppFEV₁ and fewer exacerbations. These findings highlight ETI's dual role as a therapeutic and immune-modulating agent, supporting use of cytokine profiling for personalised CF care.

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.