Yu Yan-Zhe, Gui Xian-Hua, Yu Min, Huang Wen, Peng Li-Yao, Dai Jing-Hong, Xu Qing-Qing, Zhao Ting-Ting, Xie Wei-Ping, Xiao Yong-Long, Yuan Ping, Li Yan
Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Ann Transl Med. 2022 Jul;10(14):797. doi: 10.21037/atm-22-3215.
Idiopathic pulmonary fibrosis (IPF) is a heterogeneous and progressive fibrosing interstitial lung disease with a poor prognosis. However, there are currently no effective biomarker that can reliably predict the prognosis for IPF in clinic. The serum level of soluble suppression of tumorigenicity-2 (sST2), which is involved in the immune response, has proven to be a prognostic predictor for various diseases. Previous studies have confirmed that the immune dysfunction plays an important role in the pathogenesis of IPF and the serum sST2 concentrations in patients with IPF are elevated. However, the relationship between sST2 and the prognosis of IPF remains unknown.
A total of 83 patients with IPF and 20 healthy controls from 2016 to 2021 were enrolled and demographic variables, indices of lung function testing as well as the biomarkers including the sST2 were obtained at baseline. During follow-up, the primary endpoint was defined as all-cause death and clinical deterioration. Cox hazard models and Kaplan-Meier method were used to assess the prognostic value of various indices including sST2.
Mean duration of follow-up was 29 months, during which 49 patients had an event, and of them, 35 patients died. The sST2 level was higher in the IPF patients compared with the healthy controls. Although the sST2 level did not directly predict all-cause death in the present study, it was proved to be an independent predictor of event-free survival. Multivariate forward stepwise model which was adjusted by age, sex, and body surface area (BSA) showed that the overexpression of sST2 increased the hazard ratio [1.005, 95% confidence interval (CI): 1.001-1.010]. A higher sST2 serum level heralded more deterioration and the poor outcomes. Moreover, the effect of sST2 on the prognosis of IPF may not necessarily involve the development of IPF-related pulmonary hypertension (PH).
In our study, the sST2 serum level was significantly elevated and a higher serum level of sST2 predicted more deterioration and poor outcomes in patients with IPF. Thus, sST2 can serve as a valuable prognostic biomarker for the outcome of IPF. However, further multicenter clinical trials of larger sample size are needed in the future.
特发性肺纤维化(IPF)是一种异质性、进行性纤维化间质性肺疾病,预后较差。然而,目前尚无有效的生物标志物能够在临床上可靠地预测IPF的预后。血清可溶性肿瘤抑制因子2(sST2)水平参与免疫反应,已被证明是多种疾病的预后预测指标。既往研究证实免疫功能障碍在IPF发病机制中起重要作用,且IPF患者血清sST2浓度升高。然而,sST2与IPF预后的关系仍不清楚。
纳入2016年至2021年期间的83例IPF患者和20例健康对照,收集基线时的人口统计学变量、肺功能测试指标以及包括sST2在内的生物标志物。随访期间,主要终点定义为全因死亡和临床恶化。采用Cox风险模型和Kaplan-Meier方法评估包括sST2在内的各项指标的预后价值。
平均随访时间为29个月,期间49例患者发生事件,其中35例患者死亡。IPF患者的sST2水平高于健康对照。虽然在本研究中sST2水平不能直接预测全因死亡,但它被证明是无事件生存的独立预测指标。经年龄、性别和体表面积(BSA)校正的多变量向前逐步模型显示,sST2的过表达增加了风险比[1.005,95%置信区间(CI):1.001 - 1.010]。较高的sST2血清水平预示着更多的病情恶化和不良结局。此外,sST2对IPF预后的影响不一定涉及IPF相关肺动脉高压(PH)的发生。
在我们的研究中,IPF患者血清sST2水平显著升高,较高的血清sST2水平预示着更多的病情恶化和不良结局。因此,sST2可作为IPF预后的有价值生物标志物。然而,未来需要进一步开展更大样本量的多中心临床试验。