Introduction: Prostasin is a serine protease expressed in alveolar epithelial cells where it regulates fluid and electrolyte balance via proteolysis of the epithelial sodium channel.

Aim: Determine if circulating prostasin is associated with the presence or severity of IPF.

Methods: Patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months (n=624) came from the multicenter IPF-PRO Registry. Controls (n=100) without known lung disease had a similar age and sex distribution. Plasma prostasin at enrollment was quantified by immunoassay and data were log₂ transformed. Linear regression was used to compare prostasin levels in patients with IPF vs controls and, among the IPF population, determine the association of prostasin with disease severity indicated by FVC % predicted, DL_CO % predicted, and composite physiologic index (CPI) (all measured at enrollment).

Results: The IPF cohort was mostly male (74.4%), former smokers (64.7%), with a median age of 70. Median (Q1, Q3) FVC and DL_CO % predicted were 69.2 (58.4, 79.7) and 43.2 (33.4, 51.9), respectively. About half were taking an antifibrotic (AF) drug. Prostasin levels were significantly increased in patients with IPF vs controls (log₂ fold change 0.82, p<0.001), including in patients taking AF therapy. Higher prostasin levels were associated with more severe IPF (difference in disease severity per unit increase in log₂-concentration: -6.33 for FVC, -9.55 for DLCO, 7.59 for CPI; all p<0.001). Associations were unchanged after adjustment for AF drug use.

Conclusions: Circulating prostasin highly correlates with the presence and severity of IPF and is a candidate biomarker for severity of IPF.