Introduction: Interstitial lung abnormalities (ILA) are often observed as ancillary findings of chest CT indicating early pulmonary fibrosis. Data relating to the association of the disease progression with serum biomarkers, including white blood cell differential counts and Krebs von den Lungen-6 (KL-6) is sparse in ILA.

Methods: This was a retrospective cohort study involving 159 patients who underwent blood tests including KL-6 and chest CT from October 2021 and September 2022. Clinical characteristics, pulmonary function test, chest CT, complete blood cell counts and KL-6 were analyzed in 63 patients with ILA and 74 with interstitial lung diseases (ILDs).

Results: A total of 63 patients with ILA, 54 patients with idiopathic fibrosis (IPF), and 20 patients with connective tissue disease related ILD (CTD-ILD) were enrolled. 63 patients with ILA had clinical characteristics similar to those with IPF, but not with patients with CTD-ILD. Serum KL-6 did not correlate with forced vital capacity (FVC) and diffusing capacity of the lung for CO (DLCO) in patients with ILA. Among 42 patients with ILA, 12 patients showed the radiological progression. For the radiographic progression, serum KL-6 demonstrated moderate performance with area under the curves (AUC) ranging 0.60-0.93 (p=0.008). In multivariate analysis, fibrotic ILA (odds ratio [OR] 6.99; 95% CI, 1.12?43.5) and KL-6 >400 U/mL (OR 6.52; 95% CI, 1.14?37.2) were associated with the radiological progression.

Conclusion: Serum KL-6 would be a reliable indicator for disease progression in asymptomatic patients with ILA. Radiological progression should be carefully monitored, especially if serum KL-6 is > 400 U/mL.