Todd Jamie L, Page Courtney, Wu Peitao, Belperio John A, Maher Toby M, Palmer Scott M, Leonard Thomas B, Hesslinger Christian, Neely Megan L, Schlange Thomas
Duke Clinical Research Institute, Durham, NC, USA.
Duke University Medical Center, Durham, NC, USA.
ERJ Open Res. 2025 Jun 23;11(3). doi: 10.1183/23120541.00738-2024. eCollection 2025 May.
Prostasin is expressed in the lung epithelium where it regulates fluid and electrolyte balance 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 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) 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.
前列腺素酶在肺上皮细胞中表达，在那里它调节液体和电解质平衡以及钠通道蛋白水解。我们研究了循环前列腺素酶水平是否与特发性肺纤维化（IPF）的存在和严重程度相关，以及前列腺素酶水平或其变化是否与死亡率相关。
IPF患者来自IPF-PRO注册研究。无肺部疾病的对照组年龄/性别分布相似。通过免疫测定法对入组时采集的血浆以及IPF队列中入组后约6个月的血浆中的前列腺素酶进行定量。使用线性回归比较IPF患者与对照组入组时的前列腺素酶水平，并在IPF队列中确定前列腺素酶水平与肺功能之间的关联。多变量Cox比例风险模型确定入组时的前列腺素酶水平以及6个月内前列腺素酶水平的变化与呼吸死亡之间的关联。
IPF患者（n = 624）入组时的前列腺素酶水平高于对照组（n = 100）（倍数差异1.75；p < 0.001）。在IPF队列中，前列腺素酶每1个标准差（sd）差异导致的疾病严重程度差异，对于预测的用力肺活量百分比为-3.85，对于预测的一氧化碳肺弥散量百分比为-4.24（均p < 0.001）。入组时前列腺素酶每1个标准差差异导致的呼吸死亡调整风险比（HR）为1.20（95% CI 1.04 - 1.40，p = 0.014，n = 624）。6个月内前列腺素酶变化每1个标准差差异导致的后续呼吸死亡调整HR为1.33（95% CI 1.01 - 1.74，p = 0.041，n = 290）。
循环前列腺素酶是IPF患者死亡风险的独立标志物。
