Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
PROOF Centre of Excellence, Providence Research, Vancouver, British Columbia, Canada; and.
Ann Am Thorac Soc. 2024 Dec;21(12):1688-1697. doi: 10.1513/AnnalsATS.202402-215OC.
The factors that lead to poor pulmonary exacerbation (PEx) outcomes in individuals with cystic fibrosis (CF) are still being investigated; however, delayed diagnosis and treatment are likely contributory. Identifying individuals at imminent risk of PEx could enable closer monitoring and/or earlier initiation of therapies to improve outcomes. The goal of this study was to develop blood-based biomarkers that associate with imminent PEx risk in individuals with CF. We examined the whole-blood transcriptome and 55 inflammatory proteins from plasma and serum on 72 blood samples from 53 individuals with CF. Biomarker candidate genes and proteins were selected from 14 individuals with CF with paired stable and PEx visits (cohort 1). The biomarker candidates were then estimated and tested to classify individuals with CF who would experience a PEx within 4 months of a stable clinic visit or not (cohort 2). A 16-gene panel and 9-protein panel were identified that could distinguish paired stable and PEx visits (area under the receiver operating characteristic curve [AUC] ± standard error = 0.83 ± 0.28 and 0.92 ± 0.18, respectively). These two panels also demonstrated strong performance in classifying individuals with CF who would experience a PEx within 4 months of a clinically stable visit or not (16-gene panel: AUC = 0.88; 9-protein panel: AUC = 0.83). In comparison, serum calprotectin and clinical variables (i.e., sex, precent predicted forced expiratory volume in 1 s, and the number of IV antibiotics in the preceding year) had AUCs of 0.75 and 0.71, respectively. Blood-based mRNA and protein biomarkers demonstrated strong performance in classifying individuals with CF at risk of imminent PEx. If the findings from this study can be validated, there is the potential to use blood biomarkers to enable more personalized disease activity monitoring in CF.
导致囊性纤维化（CF）患者肺部恶化（PEx）结局不佳的因素仍在研究中；然而，延迟诊断和治疗可能是促成因素。识别即将发生 PEx 风险的个体可以实现更密切的监测和/或更早地开始治疗，以改善结局。本研究的目的是开发与 CF 患者即将发生 PEx 风险相关的基于血液的生物标志物。我们检查了 53 名 CF 患者的 72 份血液样本的全血转录组和来自血浆和血清的 55 种炎症蛋白。从 14 名具有配对稳定和 PEx 就诊的 CF 患者（队列 1）中选择生物标志物候选基因和蛋白。然后估计和测试生物标志物候选物，以对在稳定就诊后 4 个月内会经历 PEx 的 CF 患者进行分类或不分类（队列 2）。确定了一个 16 基因和 9 蛋白的面板，可区分配对的稳定和 PEx 就诊（接收者操作特征曲线下面积 [AUC] ± 标准误差分别为 0.83 ± 0.28 和 0.92 ± 0.18）。这两个面板在对在临床稳定就诊后 4 个月内会经历 PEx 的 CF 患者进行分类方面也表现出良好的性能（16 基因面板：AUC = 0.88；9 蛋白面板：AUC = 0.83）。相比之下，血清钙卫蛋白和临床变量（即性别、第 1 秒用力呼气量占预计值的百分比和前一年静脉内抗生素的数量）的 AUC 分别为 0.75 和 0.71。基于血液的 mRNA 和蛋白生物标志物在对即将发生 PEx 风险的 CF 患者进行分类方面表现出良好的性能。如果本研究的结果能够得到验证，就有可能使用血液生物标志物使 CF 患者的疾病活动监测更具个性化。
