Changes in blood Krebs von den Lungen-6 predict the mortality of patients with acute exacerbation of interstitial lung disease

Abstract

Acute exacerbation (AE) significantly affects the prognosis of patients with interstitial lung disease (ILD). This study aimed to investigate the best prognostic biomarker for patients with AE-ILD. Clinical data obtained during hospitalization were retrospectively analyzed for 96 patients with AE-ILD at three tertiary hospitals. The mean age of all subjects was 70.1 years; the percentage of males was 66.7%. Idiopathic pulmonary fibrosis accounted for 60.4% of the cases. During follow-up (median: 88 days), in-hospital mortality was 24%. Non-survivors had higher lactate dehydrogenase and C-reactive protein (CRP) levels, lower ratio of partial pressure of oxygen to the fraction of inspiratory oxygen (P/F ratio), and higher relative change in Krebs von den Lungen-6 (KL-6) levels over 1 week after hospitalization than survivors. In multivariable analysis adjusted by age, the 1-week change in KL-6-along with baseline P/F ratio and CRP levels-was an independent prognostic factor for in-hospital mortality (odds ratio 1.094, P = 0.025). Patients with remarkable increase in KL-6 (≥ 10%) showed significantly worse survival (in-hospital mortality: 63.2 vs. 6.1%) than those without. In addition to baseline CRP and P/F ratio, the relative changes in KL-6 over 1 week after hospitalization might be useful for predicting in-hospital mortality in patients with AE-ILD.

Figure 1

Flowchart of patient selection. ILD interstitial lung disease, AE acute exacerbation, KL-6 Krebs von den Lungen-6.

Figure 2

Comparison of the receiver operating characteristic curve of blood markers for predicting in-hospital mortality in patients with AE-ILD. AE-ILD acute exacerbation of interstitial lung disease; ROC curves: blue line, KL-6 relative change from baseline; red line, baseline P/F ratio; green line, baseline CRP. KL-6 Krebs von den Lungen-6, P/F ratio ratio of partial pressure of oxygen to the fraction of inspiratory oxygen, CRP C-reactive protein, AUC area under the curve.

Figure 3

Comparison of survival curves after hospitalization between groups with high and low changes in KL-6 among patients with AE-ILD. Kaplan–Meier curves: blue line, high KL-6 change group; red line, low KL-6 change group. KL-6 Krebs von den Lungen-6, AE-ILD acute exacerbation of interstitial lung disease.