Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis

Respir Med. 2014 Jul;108(7):1031-9. doi: 10.1016/j.rmed.2014.04.009. Epub 2014 Apr 26.

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.

Keywords: Biomarker; Interstitial lung disease; Outcome; Survival.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Biomarkers / blood
  • Chemokines, CC / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnosis*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Assessment / methods
  • Total Lung Capacity / physiology

Substances

  • Biomarkers
  • CCL18 protein, human
  • Chemokines, CC
  • MUC1 protein, human
  • Mucin-1