Majewski Sebastian, Szewczyk Karolina, Żal Aleksandra, Białas Adam J, Miłkowska-Dymanowska Joanna, Piotrowski Wojciech J
Department of Pneumology, Medical University of Lodz, 90-153 Lodz, Poland.
Department of Pathobiology of Respiratory Diseases, Medical University of Lodz, 90-153 Lodz, Poland.
J Clin Med. 2021 Aug 28;10(17):3864. doi: 10.3390/jcm10173864.
Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (T% pred.), while SP-D levels correlated inversely with FVC% pred. and T% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF.
特发性肺纤维化（IPF）是一种具有异质性临床病程的进行性且不可避免会致命的疾病。本研究旨在评估循环生物标志物在IPF常规临床实践中的有用性。我们对一组符合抗纤维化治疗条件的28例IPF患者进行了一项探索性研究，对七种IPF生物标志物进行了长达24个月的连续测量，其中包括已被广泛认可的克雷伯斯-冯-登-卢根-6（KL-6）、表面活性蛋白D（SP-D）、基质金属蛋白酶7（MMP-7），以及最近引入的癌抗原19-9（CA19-9）、癌抗原125（CA-125）、趋化因子（C-C基序）配体18（CCL18）和骨膜蛋白。在所研究的生物标志物中，SP-D区分IPF患者与对照组的诊断准确性最高，其次是MMP-7和KL-6。在每个研究时间点，KL-6水平与预测的用力肺活量百分比（FVC%pred.）以及预测的肺一氧化碳转运因子百分比（T%pred.）呈负相关，而在抗纤维化治疗24个月时，SP-D水平与FVC%pred.和T%pred.呈负相关。与病情稳定的患者相比，病情进展患者的基线KL-6和CA19-9浓度显著升高。此外，在病情进展亚组中，CA19-9浓度在研究随访的第二年显著增加。在病情进展的患者中，我们观察到治疗第一年SP-D水平的变化与FVC%pred.的变化之间存在显著负相关，而在第二年，KL-6水平的变化与FVC%pred.的变化之间存在显著负相关。我们的研究结果支持这样一种观点，即包括KL-6、SP-D和MMP-7在内的已被广泛认可的IPF生物标志物以及最近引入的如CA19-9等生物标志物都有可能为IPF的临床实践提供支持。
