Alfaro Enrique, Casitas Raquel, Díaz-García Elena, García-Tovar Sara, Galera Raúl, Torres-Vargas María, Fernández-Velilla María, López-Fernández Cristina, Añón José M, Quintana-Díaz Manuel, García-Río Francisco, Cubillos-Zapata Carolina
Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, Madrid, Spain.
Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Madrid, Spain.
Front Immunol. 2024 Aug 29;15:1401015. doi: 10.3389/fimmu.2024.1401015. eCollection 2024.
In post-COVID survivors, transforming growth factor-beta-1 (TGF-β1) might mediate fibroblast activation, resulting in persistent fibrosis.
In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-β1 was measured in blood and exhaled breath condensate (EBC).
At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-β1. Plasma TGF-β1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-β receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-β1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment.
TGF-β1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.
在新冠康复者中，转化生长因子-β1（TGF-β1）可能介导成纤维细胞活化，导致持续性纤维化。
在本研究中，对82名新冠相关急性呼吸窘迫综合征（ARDS）康复者在重症监护病房（ICU）出院后6个月和24个月时进行了检查。在6个月时，对肺部衰减进行了定量CT分析，并测量了血液和呼出气冷凝液（EBC）中的活性TGF-β1。
在ICU出院6个月时，DmCO/肺泡体积比降低的患者血浆和EBC中的活性TGF-β1水平较高。呼吸困难的康复者血浆TGF-β1水平升高，且与高衰减肺体积直接相关。在体外，康复者的血浆和EBC以TGF-β受体依赖的方式诱导人原代成纤维细胞发生促纤维化变化。最后，在6个月时，血浆和EBC中的活性TGF-β1水平可区分出在ICU出院24个月后出现气体交换障碍的患者。
TGF-β1通路在新冠诱导的ARDS康复者早期纤维化异常中起关键作用，对长期功能损害具有重要意义。
