Villella Valeria Rachela, Castaldo Alice, Scialò Filippo, Castaldo Giuseppe
CEINGE-Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy.
SC di Pneumologia e UTSIR, AORN Santobono-Pausilipon, 80122 Naples, Italy.
Antioxidants (Basel). 2025 Mar 4;14(3):310. doi: 10.3390/antiox14030310.
A critical challenge in the age of advanced modulator therapies is to understand and determine how effectively chronic oxidative stress and oxidative stress-induced inflammation can be reversed and physiological balance restored when CFTR function is pharmacologically improved. The triple therapy with elexacaftor-tezacaftor-ivacaftor (ETI) suggests that CFTR activity in individuals with at least one F508del mutation can be partially restored to about 50% of normal levels. Although incomplete, the partial recovery of CFTR function has been shown to drastically lower sputum pathogen content, enhance microbiome diversity, and lower inflammation markers within the first year of treatment in adolescents and adults with cystic fibrosis. However, despite these advancements, residual airway infection, oxidative stress and inflammation persist, with levels similar to other chronic lung conditions, like non-CF bronchiectasis. This persistence highlights the necessity for innovative antioxidant and anti-inflammatory treatments, in particular for individuals with advanced lung disease. To address this issue, emerging multi-omics technologies offer valuable tools to investigate the impact of modulator therapies on various molecular pathways. By analyzing changes in gene expression, epigenetic modifications, protein profiles and metabolic processes in airway-derived samples, it could be possible to uncover the mechanisms driving persistent oxidative stress and inflammation. These insights could pave the way for identifying new therapeutic targets to fully restore airway health and overall physiological balance.
在先进调节剂疗法时代，一个关键挑战是理解并确定当CFTR功能通过药物得到改善时，慢性氧化应激和氧化应激诱导的炎症能够在多大程度上得到有效逆转以及生理平衡能够在多大程度上得以恢复。依列卡托-替扎卡托-依伐卡托三联疗法（ETI）表明，至少携带一个F508del突变的个体的CFTR活性能够部分恢复至正常水平的约50%。尽管并不完全，但在患有囊性纤维化的青少年和成年人接受治疗的第一年，CFTR功能的部分恢复已被证明能大幅降低痰液病原体含量、增强微生物群多样性并降低炎症标志物水平。然而，尽管有这些进展，残余的气道感染、氧化应激和炎症仍然存在，其水平与其他慢性肺部疾病（如非囊性纤维化支气管扩张）相似。这种持续性凸显了创新的抗氧化和抗炎治疗的必要性，特别是对于患有晚期肺部疾病的个体。为了解决这个问题，新兴的多组学技术提供了有价值的工具来研究调节剂疗法对各种分子途径的影响。通过分析气道来源样本中的基因表达、表观遗传修饰、蛋白质谱和代谢过程的变化，有可能揭示驱动持续性氧化应激和炎症的机制。这些见解可能为确定新的治疗靶点铺平道路，以完全恢复气道健康和整体生理平衡。
