Department of Medical Sciences, Surgery and Neuroscience, Respiratory Disease and Lung Transplant Unit, Siena University, Siena, Italy.
Department of Pulmonology, Hannover Medical School, Hannover, Germany.
Intern Med J. 2021 May;51(5):705-711. doi: 10.1111/imj.14768.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease often managed with nintedanib, a tyrosine kinase inhibitor targeting several profibrotic pathways. Although clotting processes are involved in wound healing and repair in the lung, there are no data on the role of antithrombin III (ATIII) in IPF patients treated with nintedanib. A previous proteomic analysis of serum of IPF patients before and after 1 year of nintedanib treatment showed differential protein expression of ATIII.
Here we used quantitative methods to evaluate differential ATIII concentrations in IPF patients before and after 1 year of nintedanib treatment and to assess the potential of ATIII as a prognostic biomarker in IPF patients.
Serum levels of ATIII were measured by enzyme-linked immunosorbent assay in 14 IPF patients before and after 1 year of nintedanib treatment.
A statistically significant inverse correlation was found between serum ATIII concentrations and pulmonary function test parameters in all patients at baseline and follow up. Baseline serum ATIII and bronchoalveolar lavage (BAL) neutrophils proved to be reliable predictors of poor prognosis. A baseline ATIII threshold of 126.5 μg/mL discriminated survivors from non-survivors.
After 12 months of antifibrotic treatment, IPF patients with high serum ATIII concentrations and high BAL neutrophil percentages had a poor prognosis and increased survival risk. The results of this preliminary study suggest that ATIII has potential as a biomarker of IPF severity and in predicting response to nintedanib therapy. As a marker, ATIII showed several advantages over BAL neutrophil percentage.
特发性肺纤维化（IPF）是一种进行性肺部疾病，常采用酪氨酸激酶抑制剂尼达尼布进行治疗，该抑制剂可靶向多种促纤维化途径。尽管凝血过程参与了肺部的愈合和修复，但目前尚无关于在接受尼达尼布治疗的 IPF 患者中抗凝血酶 III（ATIII）作用的数据。之前对接受尼达尼布治疗 1 年后的 IPF 患者的血清进行蛋白质组学分析显示，ATIII 的蛋白表达存在差异。
本研究使用定量方法评估 IPF 患者在接受尼达尼布治疗 1 年后 ATIII 的差异浓度，并评估 ATIII 作为 IPF 患者预后生物标志物的潜力。
通过酶联免疫吸附试验检测 14 例 IPF 患者在接受尼达尼布治疗 1 年前和治疗 1 年后的血清 ATIII 水平。
在所有患者的基线和随访时，均发现血清 ATIII 浓度与肺功能测试参数呈统计学上的显著负相关。基线血清 ATIII 和支气管肺泡灌洗液（BAL）中性粒细胞被证明是预后不良的可靠预测指标。ATIII 的基线阈值为 126.5 μg/mL，可区分存活者和非存活者。
在接受抗纤维化治疗 12 个月后，血清 ATIII 浓度高且 BAL 中性粒细胞百分比高的 IPF 患者预后不良，生存风险增加。这项初步研究的结果表明，ATIII 具有作为 IPF 严重程度和预测对尼达尼布治疗反应的生物标志物的潜力。作为标志物，ATIII 比 BAL 中性粒细胞百分比具有多项优势。
