Supplementary Material for: KL-6 as a potential predictive biomarker in fibrosing interstitial lung diseases

Background: As fibrosing interstitial lung diseases (fILDs) are associated with high mortality, monitoring of disease activity under treatment is highly relevant. Krebs von den Lungen-6 (KL-6) is associated with the presence and severity of different fILDs mainly in Asian patient populations. Objectives: Our aim was to evaluate KL-6 as a predictive biomarker in fILDs in Caucasian patients. Methods: Consecutive patients with fILDs were recruited prospectively and serum concentrations of KL-6 measured at baseline (BL), after 6 and 12 months (6M, 12M). Clinical characteristics including pulmonary function tests were assessed at 6-monthly visits and correlated with KL-6 BL levels as well as with KL-6 level changes. Results: A total of 47 fILD patients were included (mean age: 65 years, 68% male). KL-6 levels at BL were significantly higher in fILD patients than in healthy controls (n=44, mean age: 45, 23% male) (ILD: 1757±1960 U/ml vs. Control: 265±107 U/ml, p<0.0001). However, no differences were noted between ILD subgroups. KL-6 decreased significantly under therapy (6M∆BL-KL6: -486±1505 mean U/ml, p=0.032; 12M∆BL-KL6: -547±1782 mean U/ml, p=0.041) and KL-6 level changes negatively correlated with changes in pulmonary function parameters (FVC: r=-0.562, p<0.0001; DLCOSB: r=-0.405, p=0.013). While neither absolute KL-6 levels at BL nor KL-6 level changes were associated with ILD progression (FVC decline ≥10%, DLCOSB decline ≥15% or death), patients with a stable FVC showed significantly decreasing KL-6 levels (p=0.022). Conclusions: A decline of KL-6 under therapy correlated with a clinically relevant stabilization of lung function. Thus, KL-6 might serve as a predictive biomarker, which however must be determined by larger prospective cohorts.