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. 2025 May 30;20(5):e0323784.
doi: 10.1371/journal.pone.0323784. eCollection 2025.

Role of blood Krebs von Lungen-6 in predicting acute exacerbation in patients with idiopathic pulmonary fibrosis

Eun Jun Choe  1 , Ji Hoon Jang  1 , Jin Han Park  1 , So Young Jung  2 , Minyoung Her  3 , Jae Ha Lee  1
Affiliations

Role of blood Krebs von Lungen-6 in predicting acute exacerbation in patients with idiopathic pulmonary fibrosis

Eun Jun Choe et al. PLoS One. .

Abstract

Background: This study evaluated the role of blood Krebs von den Lungen-6 (KL-6) in predicting acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF).

Methods: From April 2018 to March 2023, clinical data of 233 IPF patients with baseline and follow-up KL-6 values at Haeundae Paik Hospital were retrospectively analyzed. AE was defined following the criteria proposed by Collard et al. in 2016.

Results: The mean age was 71.8 years; 79% were male. During follow-up (median: 18.7 months), 33 (14.2%) patients experienced AE. Throughout the entire period from baseline, KL-6 values were higher in the AE group compared to the non-AE group (P < 0.001), and the patterns of change over time also showed significant differences between both groups (P < 0.001). The KL-6 values in the post-exacerbation phase were higher than those in the pre-exacerbation phase among the AE group (P = 0.004). The AE group showed lower 1-year (86.4% vs. 95.9%) and 3-year (50.2% vs. 91.4%) survival rates compared to the non-AE group (P < 0.001). The occurrence of AE (hazard ratio (HR) 74.09, 95% confidence interval (CI) 31.97-171.7, P < 0.001) and higher lactate dehydrogenase (HR 1.02, 95% CI: 1.01-1.02, P < 0.001) were independently associated with mortality in patients with IPF.

Conclusions: Our data suggest that the trend in changes in KL-6 values may be utilized as a tool for predicting AE-IPF. Further research is needed to establish the clinical significance of changes in KL-6 for predicting AE-IPF and to validate the cut-off values for prediction.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of patient selection.
ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von den Lungen-6.
Fig 2
Fig 2. Comparison of the trends in KL-6 values over time between the non-AE group and the pre-exacerbation phase of the AE group.
P-value for ‘time*group’ represents interaction between group and time. KL-6, Krebs von den lungen-6; AE, acute exacerbation.
Fig 3
Fig 3. Comparative analysis of KL-6 values before and after AE in the AE group.
AE, acute exacerbation; KL-6, Krebs von den Lungen-6.
Fig 4
Fig 4. Comparison of the Kaplan-Meier survival curves according to occurrence of AE in patients with IPF.
AE, acute exacerbation; IPF, idiopathic pulmonary fibrosis.
See this image and copyright information in PMC

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