Lung ultrasound B-lines and serum KL-6 in the management of connective tissue disease-associated interstitial lung disease.
12 affiliations
- 1Department of Clinical Laboratory, Shantou Central Hospital, Shantou, Guangdong Province, China.
- 2Shantou University Medical College, Shantou, Guangdong Province, China.
- 3Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, Guangdong Province, China.
- 4Department of Radiology, Shantou Central Hospital, Shantou, Guangdong Province, China.
- 5Department of Ultrasound, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.
- 6Department of Pulmonology, Cattinara Hospital, University of Trieste, Trieste, Italy.
- 7Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
- 8Unit of Immunology, Rheumatology, Allergy and Rare diseases (UnIRAR), IRCCS San Raffaele Hospital, Milan, Italy.
- 9Vita Salute San Raffaele University, Milano, Italy.
- 10Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, USA.
- 11University of Washington, Seattle, WA, USA.
- 12Department of Experimental and Clinical Medicine, Division of Rheumatology, Careggi University Hospital, University of Florence, Florence, Italy.
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.
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BibTeX
@article{huang2026lung,
title = {{Lung ultrasound B-lines and serum KL-6 in the management of connective tissue disease-associated interstitial lung disease.}},
author = {Meigan Huang and Shaoyu Zheng and Guangzhou Du and Zexuan Zhou and Xinyi Li and Yanlin Chen and Qingzi Chen and Shijian Hu and Jianqun Lin and Kedi Zheng and Weijin Zhang and Qisheng Lin and Barbara Ruaro and Anna-Maria Hoffmann-Vold and Marco Matucci-Cerinic and Daniel E Furst and Shaoqi Chen and Yukai Wang},
journal = {Rheumatology and immunology research},
year = {2026},
month = oct,
doi = {10.1515/rir-2026-0020},
url = {https://europepmc.org/article/MED/42924232},
note = {CC BY},
}
RIS
TY - JOUR
TI - Lung ultrasound B-lines and serum KL-6 in the management of connective tissue disease-associated interstitial lung disease.
AU - Meigan Huang
AU - Shaoyu Zheng
AU - Guangzhou Du
AU - Zexuan Zhou
AU - Xinyi Li
AU - Yanlin Chen
AU - Qingzi Chen
AU - Shijian Hu
AU - Jianqun Lin
AU - Kedi Zheng
AU - Weijin Zhang
AU - Qisheng Lin
AU - Barbara Ruaro
AU - Anna-Maria Hoffmann-Vold
AU - Marco Matucci-Cerinic
AU - Daniel E Furst
AU - Shaoqi Chen
AU - Yukai Wang
PY - 2026
DA - 2026/10/22
JO - Rheumatology and immunology research
DO - 10.1515/rir-2026-0020
UR - https://europepmc.org/article/MED/42924232
AB - 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.
SN - 2719-4523
ER -