Abstract
Simple SummaryEvaluation of the prognostic significance of serial measurements of serum concentrations of Krebs von den Lungen-6 (KL-6) showed that an annual increment in KL-6 exceeding a threshold amount was an independent risk factor for progressive disease and poor prognosis. No literature data are available on long-term KL-6 measurements in the follow-up of IPF patients treated with Nintedanib. The aim of this study is to serially analyze KL-6 in idiopathic pulmonary fibrosis (IPF) patients after 24 months of Nintedanib and to investigate its biomarker potential in patients with IPF and lung cancer with respect to fibrotic hypersensitivity pneumonitis patients, pulmonary fibrosis associated with autoimmune diseases group and healthy controls.Background: 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. Materials and methods: 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). Results: 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. Conclusion: 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.
Highlights
Krebs von den Lungen-6 (KL-6) is a high-molecular-weight (200 kDa) glycoprotein predominantly expressed in the lungs by injured and regenerating alveolar type II cells [1,2]
Serum concentrations of KL-6 were higher in idiopathic pulmonary fibrosis (IPF)-LC than IPF patients at t0 (p = 0.0002) (Table 1) and receiver operating characteristic (ROC) curve analysis distinguished these two groups (AUC 92%; 95% CI 78-100; p = 0.0005), indicating a best cut-off value of 1370 U/mL (83% sensitivity, 92% specificity) (Figure 2)
Significant differences were observed between patients with idiopathic pulmonary fibrosis associated with lung canc (IPF-LC) and fibrotic hypersensitivity pneumonitis (p = 0.0001) and healthy controls (p < 0.0001)
Summary
Krebs von den Lungen-6 (KL-6) is a high-molecular-weight (200 kDa) glycoprotein predominantly expressed in the lungs by injured and regenerating alveolar type II cells [1,2]. KL-6 was proposed as a diagnostic biomarker for differentiating interstitial lung diseases (ILDs) and predicting response to antifibrotic therapy [4,5,6]. A cut-off value of 465 U/mL was recently established to distinguish ILD patients from the healthy subjects and patients with other non-fibrotic lung diseases [7], the potential value of KL-6 as a biomarker in the differential diagnosis of ILDs is still limited [8,9]. Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). 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. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
