Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis.
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.
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.
Shinichiro
S
Ohshimo
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nobuhi@hiroshima-u.ac.jp.
Nobuhisa
N
Ishikawa
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: yasushi17@hiroshima-u.ac.jp.
Yasushi
Y
Horimasu
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nhattori@hiroshima-u.ac.jp.
Noboru
N
Hattori
Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: hirohasi@hiroshima-u.ac.jp.
Nobuyuki
N
Hirohashi
Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: tanigawa@hiroshima-u.ac.jp.
Koichi
K
Tanigawa
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nokohno@hiroshima-u.ac.jp.
Nobuoki
N
Kohno
Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Essen, Germany. Electronic address: francesco.bonella@ruhrlandklinik.uk-essen.de.
Francesco
F
Bonella
General and Experimental Pathology, Ruhr-University, Bochum, Germany. Electronic address: josune.guzman@ruhr-uni-bochum.de.
Josune
J
Guzman
Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de.
Ulrich
U
Costabel
D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019742:Chemokines, CC / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D014109:Total Lung Capacity / Q000502:physiology
D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC; C060192:MUC1 protein, human; D018396:Mucin-1
Biomarker; Interstitial lung disease; Outcome; Survival