Introduction: Cystatin C was reported to be functional in the lung fibrosis process. This study aimed to evaluate the association of serum Cystatin C level with Interstitial lung abnormalities (ILAs), features of incidental findings on chest computed tomography (CT) that probably represent the early morphologic changes of interstitial lung disease.

Methods: Data from 3,300 individuals with ILAs who were identified by low-dose chest CT scans during health checkups at a large Chinese hospital were used. The serum Cystatin C level were extracted from electronic medical records. Mann-Whitney test was used to conduct between-group differences.

Results: Individuals with reticulation (0.95[0.90-1.10] vs.0.93[0.83-1.01], P<0.0001), non-emphysematous cysts (1.00[0.94-1.16] vs. 0.94[0.86-1.04], P=0.0428), traction bronchiectasis (0.97[0.91-1.16] vs.0.94[0.86-1.04], P=0.0001), and honeycombing (1.06[0.94-1.25] vs.0.94[0.86-1.04], P<0.0001) had higher serum cystatin C level than individuals without these imaging features. Inversely, individuals with ground-glass opacities (GGO) had lower serum cystatin C level than individuals without this feature (0.94[0.86-1.04] vs.0.97[0.87-1.09], P=0.0439). Individuals with subpleural fibrotic ILAs had significantly higher serum cystatin C level than individuals with subpleural non-fibrotic ILAs (1.00[0.94-1.21] vs.0.94[0.86-1.03], P<0.0001) and non-subpleural ILAs (1.00[0.94-1.21] vs.0.94[0.85-1.05], P<0.0001).

Conclusions: Individuals with fibrotic-like ILAs features and patterns had higher serum Cystatin C level than those without, indicating Cystatin C may participate in pulmonary fibrogenesis even in the early phase.