Lung ultrasound B-lines and serum KL-6 in the management of connective tissue disease-associated interstitial lung disease
Meigan Huang, Shaoyu Zheng, Guangzhou Du, Zexuan Zhou, Xinyi Li, Yanlin Chen, Qingzi Chen, Shijian Hu, Jianqun Lin, Kedi Zheng, Weijin Zhang, Qisheng Lin, Barbara Ruaro, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Daniel E Furst, Shaoqi Chen, Yukai WangAbstract
Background and Objectives
Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with connective tissue diseases (CTDs). Early diagnosis, appropriate intervention, and close monitoring are critical to mitigate the progression of CTD-ILD. Lung ultrasound (LUS) B-lines and serum Krebs von den Lungen-6 (KL-6) have emerged as promising, non-invasive, and radiation-free biomarkers for ILD. This single-center retrospective study aimed to evaluate the combined diagnostic and assessment value of B-lines and KL-6 in patients with CTD-ILD.
Methods
A total of 226 consecutive patients with CTD who underwent high resolution computed tomography (HRCT), LUS and serum KL-6 testing within a one-month interval were retrospectively enrolled. Based on HRCT findings, patients were classified into ILD and non-ILD groups. Those with ILD were further subdivided into fibrotic ILD (F-ILD) and non-fibrotic ILD (NF-ILD) according to radiographic patterns. LUS was performed across 50 scanning sites, and the total number of B-lines was calculated as a B-lines number. Correlations between B-lines number, KL-6 level, and HRCT Warrick score were analyzed. The diagnostic accuracy of LUS B-lines and KL-6, individually and in combination, for detecting ILD and F-ILD was determined using receiver operating characteristic (ROC) curve analysis. The ability of B-lines and KL-6 to discriminate ILD severity based on the HRCT Warrick score was assessed.
Results
The ILD group demonstrated significantly higher B-lines number and serum KL-6 levels compared to the non-ILD group ( P < 0.001). ROC analysis showed good diagnostic performance for both B-lines (AUC = 0.85 [95% CI: 0.80–0.90]; sensitivity = 77.6%; specificity = 77.0%) and KL-6 (AUC = 0.79 [95% CI: 0.73–0.85]; sensitivity = 58.6%; specificity = 91.9%). The combination of both markers further improved diagnostic accuracy (AUC = 0.87 [95% CI: 0.82–0.91]; sensitivity = 74.3%; specificity = 86.5%). Both B-lines number and KL-6 level showed significant positive correlations with the HRCT Warrick score. Notably, B-lines number and serum KL-6 were able to distinguish between F-ILD and NF-ILD subtypes (both P < 0.001) and were associated with disease severity ( P < 0.001 for B-lines; P = 0.016 for KL-6).
Conclusion
Both LUS B-lines and serum KL-6 are valuable biomarkers for diagnosing and assessing CTD-ILD, and their combination enhances diagnostic accuracy.