Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease
Takanori Asakura
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan
Japan Society for the Promotion of Science, Tokyo, Japan
T.A. and Y.K. contributed equally to this study.
Search for more papers by this authorYoshifumi Kimizuka
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
T.A. and Y.K. contributed equally to this study.
Search for more papers by this authorCorresponding Author
Tomoyasu Nishimura
Keio University Health Center, Tokyo, Japan
Correspondence: Tomoyasu Nishimura, Keio University Health Center, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Email: [email protected]Search for more papers by this authorShoji Suzuki
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorHo Namkoong
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorYohei Masugi
Department of Pathology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorYasunori Sato
Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorMakoto Ishii
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorNaoki Hasegawa
Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorTakanori Asakura
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan
Japan Society for the Promotion of Science, Tokyo, Japan
T.A. and Y.K. contributed equally to this study.
Search for more papers by this authorYoshifumi Kimizuka
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
T.A. and Y.K. contributed equally to this study.
Search for more papers by this authorCorresponding Author
Tomoyasu Nishimura
Keio University Health Center, Tokyo, Japan
Correspondence: Tomoyasu Nishimura, Keio University Health Center, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Email: [email protected]Search for more papers by this authorShoji Suzuki
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorHo Namkoong
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorYohei Masugi
Department of Pathology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorYasunori Sato
Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorMakoto Ishii
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorNaoki Hasegawa
Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorABSTRACT
Background and objective
The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response.
Methods
Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187).
Results
The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion.
Conclusion
Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.
Supporting Information
| Filename | Description |
|---|---|
| resp13886-sup-0001-Supinfo.docxWord 2007 document , 7.4 MB | Appendix S1 Additional methods. Table S1 Comparison of the clinical characteristics of healthy control patients and age-matched patients with MAC-LD. Table S2 Comparison of the clinical characteristics of patients with bronchiectasis without NTM and age- and sex-matched patients with MAC-LD. Table S3 Baseline characteristics of all patients with MAC-LD. Table S4 Multivariable analysis of factors associated with mortality in 281 patients with MAC-LD. Figure S1 (A) Comparison of the serum Krebs von den Lungen-6 (KL-6) levels between patients with bronchiectasis without nontuberculous mycobacteria (NTM) and age- and sex-matched patients with Mycobacterium avium complex lung disease (MAC-LD). The association between serum KL-6 and modified Reiff score in (B) bronchiectasis without NTM, (C) MAC-LD and (D) both. Figure S2 Representative characteristics of patients with MAC-LD with high serum KL-6. Figure S3 Distribution of the serum KL-6 level in 281 patients with MAC-LD. Figure S4 Association between serum KL-6 and pulmonary function test results. Figure S5 Kaplan–Meier survival curves of patients with MAC-LD based on serum KL-6. Figure S6 The delta KL-6 levels in patients with disease progression stratified by radiological outcome. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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