Performance of Circulating Inflammatory Biomarkers and Krebs von den Lungen 6 for Predicting Progressive Pulmonary...

To assess the predictive performance of inflammatory biomarkers, including C-reactive protein (CRP) and Krebs von den Lungen 6 (KL-6), for the development of progressive pulmonary fibrosis (PPF) in patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD).

A total of 135 patients with SSc-ILD were retrospectively selected from a single-center prospective registry. The predictive performance of individual biomarkers and their combinations for PPF development was evaluated using area under the curve (AUC) values from receiver operating characteristic analysis. A time-varying Cox proportional hazards model was used to assess the prognostic significance of near-term dynamic changes in KL-6 levels.

During a median follow-up of 43 months, 26 patients (19%) developed PPF. Baseline CRP and KL-6 levels did not correlate with each other. Patients with high baseline KL-6 (≥1,000 U/mL) had more extensive ILD and reduced forced vital capacity compared to those with low levels. Baseline KL-6 demonstrated superior predictive performance for ILD progression (with the highest AUC) compared to CRP. The PPF-free survival rate was significantly lower in the high KL-6 group than in the low KL-6 group (P = 0.02). A doubling of KL-6 levels at any time from 12 months to 6 months before PPF assessment or censoring was associated with a significantly higher risk of subsequent PPF development (hazard ratio 1.66 [95% confidence interval 1.13-2.45]).

Baseline KL-6 and CRP values identify distinct subsets of SSc-ILD patients. Elevated baseline KL-6 levels and a significant rise over the subsequent six months are associated with an increased risk of PPF, supporting their potential as prognostic biomarkers.