title: Elevated Serum Krebs von den Lungen-6 in Early Disease Predicts Subsequent Deterioration of Pulmonary Function in Patients with Systemic Sclerosis and Interstitial Lung Disease.
abstract: To identify predictors of poor prognosis in patients with systemic sclerosis (SSc) associated with interstitial lung disease (ILD).
  
  
  
  Fifty patients with early-stage SSc-ILD who had never received disease-modifying drugs and were either observed for ≥ 10 years or died from ILD-related causes were enrolled. The baseline variables of patients who developed endstage lung disease (ESLD) were compared with those of patients who remained ESLD-free, and the Cox proportional hazard model was used to identify initial factors that correlated with ESLD development.
  
  
  
  Sixteen patients (32%) developed ESLD during 173.5 ± 64.7 months of followup. Elevated serum Krebs von den Lungen-6 (KL-6) at initial assessment was highly correlated with ESLD development (p = 0.0002). Receiver-operating characteristic curve analysis revealed that a KL-6 value of 1273 U/ml effectively discriminated patients who developed ESLD from those who did not. Patients with KL-6 > 1273 U/ml were less likely to remain ESLD-free compared with those with lower KL-6 levels (p < 0.0001). Multivariate analysis showed that KL-6 > 1273 U/ml was the most reliable predictor of ESLD development (OR 51.2, 95% CI 7.6-343, p < 0.0001). Finally, the initial KL-6 level correlated with the forced vital capacity (FVC) decline rate (r = 0.58, p < 0.0001).
  
  
  
  The natural course of SSc-ILD is highly variable. Baseline serum KL-6 is a biomarker potentially useful for predicting FVC decline.
authors.affiliation: From the Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.M. Kuwana, MD, PhD, Professor, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Y. Shirai, MD, PhD, Instructor, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; T. Takeuchi, MD, PhD, Professor, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine. kuwanam@nms.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
authors.affiliation: From the Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.M. Kuwana, MD, PhD, Professor, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Y. Shirai, MD, PhD, Instructor, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; T. Takeuchi, MD, PhD, Professor, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shirai
authors.affiliation: From the Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.M. Kuwana, MD, PhD, Professor, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Y. Shirai, MD, PhD, Instructor, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; T. Takeuchi, MD, PhD, Professor, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011237:Predictive Value of Tests; D012042:Registries; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1
keywords: INTERSTITIAL LUNG DISEASE; OUTCOME ASSESSMENT; SURVIVAL ANALYSIS; SYSTEMIC SCLEROSIS