[Predictive value of baseline serum KL-6 for acute exacerbation in fibrotic interstitial lung disease]

Objective: To investigate the predictive value of baseline serum KL-6 levels for acute exacerbation (AE) in patients with fibrotic interstitial lung disease (F-ILD). Methods: A single-center retrospective cohort study was conducted, enrolling 265 patients with fibrotic ILD diagnosed by multidisciplinary team (MDT) at Sichuan Provincial People's Hospital from July 2022 to November 2024, including 118 patients with idiopathic pulmonary fibrosis (IPF) and 147 patients with fibrotic connective tissue disease-associated ILD (CTD-ILD). Baseline data were collected, and the primary endpoint was the occurrence of AE during follow-up. Cox regression analysis was used to identify independent risk factors for AE, and ROC curve analysis was performed to evaluate predictive performance. Results: After a median follow-up of 20 months, 77 patients (29.1%) developed AE. Multivariate Cox regression showed that KL-6≥1 363.5 U/ml (HR=3.928, P<0.001) was an independent risk factor for AE. Baseline KL-6 predicted AE in F-ILD with an AUC of 0.795, and the optimal cutoff value was 1 363.5 U/ml. The combined model (KL-6+CA15-3+CYFRA21-1+D_LCO%) achieved an AUC of 0.853. Subgroup analysis revealed that KL-6 had the highest predictive value in IPF patients (AUC=0.820), followed by CTD-ILD patients (AUC=0.774). Conclusion: Baseline serum KL-6 is an independent predictor of AE in patients with F-ILD, demonstrating good risk stratification capability, particularly with optimal performance in IPF.