# Circulating prostasin is an independent marker of mortality risk in patients with idiopathic pulmonary fibrosis

## TL;DR

High levels of a protein called prostasin in the blood are linked to higher risk of death in patients with a lung disease called idiopathic pulmonary fibrosis.

## Contribution

This study identifies circulating prostasin as an independent mortality risk marker in idiopathic pulmonary fibrosis patients.

## Key findings

- Prostasin levels were significantly higher in IPF patients compared to controls.
- Higher prostasin levels at enrollment were associated with worse lung function and increased mortality risk.
- Changes in prostasin levels over six months also predicted mortality risk.

## Abstract

Prostasin is expressed in the lung epithelium where it regulates fluid and electrolyte balance via sodium channel proteolysis. We investigated whether circulating prostasin levels are associated with the presence and severity of idiopathic pulmonary fibrosis (IPF) and whether prostasin levels, or changes in them, are associated with mortality.

Patients with IPF came from the IPF-PRO Registry. Controls without lung disease had a similar age/sex distribution. Prostasin was quantified in plasma taken at enrolment and, in the IPF cohort, ∼6 months post-enrolment, by immunoassay. Linear regression was used to compare prostasin levels at enrolment in patients with IPF versus controls and, in the IPF cohort, determine associations between prostasin level and lung function. Multivariable Cox proportional hazards models determined associations between prostasin level at enrolment and change in prostasin level over 6 months and respiratory death.

Prostasin level at enrolment was higher in patients with IPF (n=624) versus controls (n=100) (fold-difference 1.75; p<0.001). In the IPF cohort, the difference in disease severity per 1 standard deviation (sd) difference in prostasin was −3.85 for forced vital capacity % predicted and −4.24 for diffusing capacity of the lung for carbon monoxide % predicted (both p<0.001). The adjusted hazard ratio (HR) for respiratory death per 1 sd difference in prostasin at enrolment was 1.20 (95% CI 1.04–1.40, p=0.014, n=624). The adjusted HR for subsequent respiratory death per 1 sd difference in change in prostasin over 6 months was 1.33 (95% CI 1.01–1.74, p=0.041, n=290).

Circulating prostasin is an independent marker of mortality risk in patients with IPF.

In patients with idiopathic pulmonary fibrosis in the IPF-PRO Registry, the circulating level of prostasin was an independent marker of mortality risk
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