Bene Zsolt, Fejes Zsolt, Macek Milan, Amaral Margarida D, Balogh István, Nagy Béla
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Clin Chim Acta. 2020 Sep;508:277-286. doi: 10.1016/j.cca.2020.05.015. Epub 2020 May 16.
Although the clinical outcomes of cystic fibrosis (CF) have been markedly improved through the recent implementation of novel CF transmembrane conductance regulator (CFTR) modulator drugs, robust and reliable biomarkers are still demanded for the early detection of CF lung disease progression, monitoring treatment efficacy and predicting life-threatening clinical complications. Thus, there is an unmet need to identify and validate novel, ideally blood based biomarkers with strong correlations to the severity of CF lung disease, which represents a major contribution to overall CF morbidity and mortality. In this review, we aim to summarize the utility of thus far studied blood-, sputum- and bronchoalveolar lavage (BAL)-based biomarkers to evaluate inflammatory conditions in the lung and to follow treatment efficacy in CF. Measurements of sweat chloride concentrations and the spirometric parameter FEV are currently utilized to monitor CFTR function and the effect of various CF therapies. Nonetheless, both have inherent pitfalls and limitations, thus routinely analyzed biomarkers in blood, sputum or BAL samples are required as surrogates for lung disorders. Recent discovery of new protein (e.g. HE4) and RNA-based biomarkers, such as microRNAs may offer a higher efficacy, which in aggregate may be valuable to evaluate disease prognosis and to substantiate CF drug efficacy.
尽管通过近期新型囊性纤维化跨膜传导调节因子（CFTR）调节剂药物的应用，囊性纤维化（CF）的临床结局已得到显著改善，但仍需要强大且可靠的生物标志物用于CF肺部疾病进展的早期检测、监测治疗效果以及预测危及生命的临床并发症。因此，识别和验证与CF肺部疾病严重程度密切相关的新型、理想的血液生物标志物的需求尚未得到满足，这对CF总体发病率和死亡率具有重要意义。在本综述中，我们旨在总结迄今为止研究的基于血液、痰液和支气管肺泡灌洗（BAL）的生物标志物在评估肺部炎症状况和跟踪CF治疗效果方面的应用。目前，汗液氯化物浓度测量和肺功能参数第一秒用力呼气容积（FEV）被用于监测CFTR功能和各种CF治疗的效果。然而，两者都有其固有的缺陷和局限性，因此需要将血液、痰液或BAL样本中常规分析的生物标志物作为肺部疾病的替代指标。新蛋白质（如人附睾蛋白4，HE4）和基于RNA的生物标志物（如微小RNA）的最新发现可能具有更高的效能，总体而言，这对于评估疾病预后和证实CF药物疗效可能具有重要价值。
