Predictive ability of longitudinal changes in Kerbs von Lungren 6 for acute exacerbation of fibrotic interstitial lung disease: Database research

Abstract

Abstract Background Acute exacerbation (AE) in fibrotic interstitial lung diseases (ILDs) poses a significant challenge, with limited available evidence for predicting such events. Kerbs von Lungren 6 (KL-6) is a proposed predictive marker for prospective AE; however, only its baseline value has been evaluated. To address this gap, this study investigates the association between the patient-specific evolution of serum KL-6 levels and the AE risk of fibrotic ILD. Methods This study used data from the Japanese Database of Health, Clinic, and Education Information Evaluation Institute and JMDC Inc. The included patients had fibrotic ILDs and antifibrotic therapy with ≥ 2 measurements of serum KL-6 from the index date to the end of follow-up. The outcome was AE of acute or chronic fibrotic ILDs defined based on the combination of its primary diagnoses, emergency admission, and pulse/high-dose steroids on the day of or after admission. We used a joint regression model for each patient’s serial serum KL-6 measurements and a proportional hazards regression model for the hazard ratio of AE. Results The study included 939 patients with fibrotic ILDs, and 194 (21%) experienced AE during the follow-up (event rate, 0.13/person-year; 1-year incidence, 35%). The hazard ratio of AE comparing patients differing in cumulative serum KL-6 was 1.54 (95% confidence interval: 1.20–1.98, p < 0.001). Conclusions A high baseline KL-6 level and its upward evolution can predict the AE of fibrotic ILD. Longitudinal KL -6 measurement should be considered, especially for patients who cannot perform pulmonary function tests well. Our study could help develop strategies for improving fibrotic ILD prognosis and treatment.