d'Alessandro Miriana, Bergantini Laura, Cameli Paolo, Pieroni Maria, Refini Rosa Metella, Sestini Piersante, Bargagli Elena
Respiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, 53100 Siena, Italy.
Cancers (Basel). 2021 Feb 9;13(4):689. doi: 10.3390/cancers13040689.
Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib and to first investigate the biomarker behavior in IPF associated with adenocarcinoma.
One hundred and forty-two ILD patients (median (IQR), 69 (63-75) years; 86 males) were retrospectively enrolled. Serial serum samples were collected from IPF patients before starting antifibrotic therapy and after 12 months. Serum KL-6 levels were measured by KL-6 reagent assay (Fujirebio Europe, UK).
Increased KL-6 concentrations were identified in IPF-LC patients than IPF, fibrotic hypersensitivity pneumonitis, and pulmonary fibrosis associated with autoimmune disease groups. A cut-off value was calculated to distinguish IPF and IPF-LC patients. IPF patients monitored for 24 months with Nintedanib showed persisted increased levels of KL-6 with a progressive decline of FVC percentages.
This preliminary study offers a first demonstration that very high serum concentrations of KL-6 in IPF-LC patients are associated with poor prognosis. Moreover, serial evaluation of serum KL-6 in IPF patients over 24 months of Nintedanib treatment revealed that most patients experienced a stabilization of lung function parameters and of serum concentrations of KL-6.
肺 Krebs von den Lungen-6(KL-6)被认为是包括特发性肺纤维化(IPF)在内的间质性肺疾病(ILD)生物标志物。肺癌是 IPF 患者最严重的合并症之一。本研究旨在对接受尼达尼布治疗 24 个月后的 IPF 患者进行 KL-6 的系列分析,并首次研究与腺癌相关的 IPF 中的生物标志物行为。
回顾性纳入 142 例 ILD 患者(中位年龄(四分位间距),69(63 - 75)岁;86 例男性)。在抗纤维化治疗开始前和 12 个月后从 IPF 患者中采集系列血清样本。血清 KL-6 水平通过 KL-6 试剂检测法(英国富士瑞必欧欧洲公司)进行测定。
与 IPF、纤维化性过敏性肺炎以及与自身免疫性疾病相关的肺纤维化组相比,IPF - 肺癌(IPF-LC)患者中 KL-6 浓度升高。计算出一个临界值以区分 IPF 和 IPF-LC 患者。接受尼达尼布治疗 24 个月的 IPF 患者显示 KL-6 水平持续升高,同时用力肺活量(FVC)百分比逐渐下降。
这项初步研究首次证明,IPF-LC 患者血清 KL-6 浓度极高与预后不良相关。此外,对接受尼达尼布治疗 24 个月以上的 IPF 患者进行血清 KL-6 的系列评估发现,大多数患者的肺功能参数和血清 KL-6 浓度趋于稳定。