Lung ultrasound B-lines and serum KL-6 in the management of connective tissue disease-associated interstitial lung disease

Abstract

Abstract 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.