Predictive Association of CYFRA 21-1 with Quantitative CT–Defined Fibrotic Progression in Idiopathic Pulmonary Fibrosis

Background and objective Although cytokeratin-19 fragment CYFRA 21 − 1 is a potential biomarker for idiopathic pulmonary fibrosis (IPF), its relationship to imaging-based structural progression remains unclear. We evaluated whether baseline CYFRA 21 − 1 is associated with fibrotic progression measured via quantitative computed tomography (QCT) and compared these associations with Krebs von den Lungen-6 (KL-6), including longitudinal relationships between changes in serum biomarker levels and QCT measures. Methods We retrospectively analyzed 101 patients with IPF who underwent volumetric chest CT, serum biomarker analysis including CYFRA 21 − 1 and KL-6, and pulmonary function tests at baseline and approximately 1 year. QCT measurements, including fibrosis, inflammation, and total interstitial lung disease extent, were measured using deep learning-based software. Results Baseline CYFRA 21 − 1 was associated with QCT-defined fibrotic progression (odds ratio per 1 ng/mL increase, 1.365; 95% confidence interval [CI], 1.017–1.833). Baseline KL-6 was also associated with fibrotic progression (odds ratio per 100 U/mL increase, 1.082; 95% CI, 1.010–1.159), although the strength of association was lower. Longitudinal increases in CYFRA 21 − 1 were associated with progression of QCT-defined fibrosis (β = 0.943; 95% CI, 0.287–1.600), whereas changes in KL-6 were more closely associated with QCT-defined inflammation (β = 0.429; 95% CI, 0.179–0.680). Neither biomarker was associated with pulmonary function-based progression. Conclusions CYFRA 21 − 1 was independently associated with QCT-defined fibrotic progression in IPF. Whereas KL-6 more closely reflected inflammatory and total interstitial lung disease CT components, CYFRA 21 − 1 preferentially captured longitudinal fibrotic remodeling, supporting complementary roles in imaging-based disease monitoring.