Shinichiro Ohshimo1, Nobuhisa Ishikawa2, Yasushi Horimasu3, Noboru Hattori4, Nobuyuki Hirohashi5, Koichi Tanigawa6, Nobuoki Kohno7, Francesco Bonella8, Josune Guzman9, Ulrich Costabel10. 1. Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: ohshimos@hiroshima-u.ac.jp. 2. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nobuhi@hiroshima-u.ac.jp. 3. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: yasushi17@hiroshima-u.ac.jp. 4. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nhattori@hiroshima-u.ac.jp. 5. Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: hirohasi@hiroshima-u.ac.jp. 6. Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: tanigawa@hiroshima-u.ac.jp. 7. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nokohno@hiroshima-u.ac.jp. 8. Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Essen, Germany. Electronic address: francesco.bonella@ruhrlandklinik.uk-essen.de. 9. General and Experimental Pathology, Ruhr-University, Bochum, Germany. Electronic address: josune.guzman@ruhr-uni-bochum.de. 10. Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de.
Abstract
BACKGROUND: Acute exacerbation (AE) is a major cause of death in idiopathic pulmonary fibrosis (IPF). However, little is known about sensitive biomarkers for predicting AE. The aim of our study was to investigate the significance of KL-6 and CC-Chemokine Ligand 18 (CCL18) as predictors for AE of IPF. METHODS: We prospectively collected a total of 77 patients with IPF. Serum levels of KL-6 and CCL18 were measured by ELISA. The correlation between baseline serum levels of the markers and the incidence of AE was evaluated. RESULTS: Thirteen (17%) patients experienced AE during follow-up. Baseline serum KL-6 levels were significantly higher in patients who developed AE than in patients with stable IPF (p < 0.0001), whereas serum CCL18 levels showed no difference between these groups (p = 0.13). At a cut-off level of 1300 U/mL for KL-6, the sensitivity, specificity, accuracy and likelihood ratio to predict AE were 92%, 61%, 66% and 2.36, respectively. In the Kaplan-Meier analysis, patients with baseline serum KL-6 level ≥1300 U/mL experienced earlier onset of AE (p = 0.002), whereas CCL18 showed no predictive value (p = 0.11). In the multivariate analysis, baseline serum KL-6 (both continuous and at a cut-off level of ≥1300 U/mL) was an independent predictive factor for AE after adjustment for age, sex, smoking history and %vital capacity (hazard ratio = 1.001, 18.8; p = 0.010, 0.008, respectively). CONCLUSIONS: Baseline serum KL-6 level is a sensitive predictor for the onset of AE in IPF.
BACKGROUND: Acute exacerbation (AE) is a major cause of death in idiopathic pulmonary fibrosis (IPF). However, little is known about sensitive biomarkers for predicting AE. The aim of our study was to investigate the significance of KL-6 and CC-Chemokine Ligand 18 (CCL18) as predictors for AE of IPF. METHODS: We prospectively collected a total of 77 patients with IPF. Serum levels of KL-6 and CCL18 were measured by ELISA. The correlation between baseline serum levels of the markers and the incidence of AE was evaluated. RESULTS: Thirteen (17%) patients experienced AE during follow-up. Baseline serum KL-6 levels were significantly higher in patients who developed AE than in patients with stable IPF (p < 0.0001), whereas serum CCL18 levels showed no difference between these groups (p = 0.13). At a cut-off level of 1300 U/mL for KL-6, the sensitivity, specificity, accuracy and likelihood ratio to predict AE were 92%, 61%, 66% and 2.36, respectively. In the Kaplan-Meier analysis, patients with baseline serum KL-6 level ≥1300 U/mL experienced earlier onset of AE (p = 0.002), whereas CCL18 showed no predictive value (p = 0.11). In the multivariate analysis, baseline serum KL-6 (both continuous and at a cut-off level of ≥1300 U/mL) was an independent predictive factor for AE after adjustment for age, sex, smoking history and %vital capacity (hazard ratio = 1.001, 18.8; p = 0.010, 0.008, respectively). CONCLUSIONS: Baseline serum KL-6 level is a sensitive predictor for the onset of AE in IPF.
Authors: Mac B Robinson; Deepak A Deshpande; Jeffery Chou; Wei Cui; Shelly Smith; Carl Langefeld; Annette T Hastie; Eugene R Bleecker; Gregory A Hawkins Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-05-22 Impact factor: 5.464
Authors: Ellyse Cipolla; Amanda J Fisher; Hongmei Gu; Elizabeth A Mickler; Manisha Agarwal; Carol A Wilke; Kevin K Kim; Bethany B Moore; Ragini Vittal Journal: FASEB J Date: 2017-08-17 Impact factor: 5.191