急性呼吸窘迫综合征中的血浆前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）
Plasma Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in the Acute Respiratory Distress Syndrome.
作者信息
Metkus Thomas S, Kim Bo Soo, Jones Steven R, Martin Seth S, Schulman Steven P, Leucker Thorsten M
机构信息
Divisions of Cardiology and Cardiac Surgery, Departments of Medicine and Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
出版信息
Front Med (Lausanne). 2022 Jun 13;9:876046. doi: 10.3389/fmed.2022.876046. eCollection 2022.
BACKGROUND
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is a mediator of the immune response to sepsis. PCSK9 is also highly expressed in pneumocytes and pulmonary endothelial cells. We hypothesized that serum PCSK9 levels would be associated with death and ICU outcomes in patients with ARDS.
METHODS
Using data and plasma samples from the NIH BioLINCC data repository, we assembled a cohort of 1,577 patients with the acute respiratory distress syndrome (ARDS) enrolled in two previously completed clinical trials, EDEN and SAILS. We measured PCSK9 levels in plasma within 24 h of intubation using commercially available ELISA kits (R&D Systems). We assessed the association of PCSK9 with mortality using Cox proportional hazard models. We also assessed clinical factors associated with PCSK9 level and the association of PCSK9 with the number of days free of mechanical ventilation and days free of ICU care.
RESULTS
In 1,577 ARDS patients, median age was 53 years (IQR 42-65 years) and median APACHE III score 91 (72-111) connoting moderate critical illness. PCSK9 levels were 339.3 ng/mL (IQR 248.0-481.0). In multivariable models, race, cause of ARDS, body mass index, pre-existing liver disease, body temperature, sodium, white blood cell count and platelet count were associated with PCSK9 level. Presence of sepsis, use of vasopressors and ventilator parameters were not associated with PCSK9 level. PCSK9 levels were not associated with in-hospital mortality (HR per IQR 0.96, 95% CI 0.84-1.08, = 0.47). Higher PCSK9 levels were associated with fewer ICU and ventilator free days.
CONCLUSIONS
Plasma PCSK9 is not associated with mortality in ARDS, however higher PCSK9 levels are associated with secondary outcomes of fewer ICU free and ventilator free days. Clinical factors associated with PCSK9 in ARDS are largely unmodifiable. Further research to define the mechanism of this association is warranted.
背景
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）是一种丝氨酸蛋白酶，是脓毒症免疫反应的介质。PCSK9在肺细胞和肺内皮细胞中也高度表达。我们推测血清PCSK9水平与急性呼吸窘迫综合征（ARDS）患者的死亡及重症监护病房（ICU）结局相关。
方法
利用美国国立卫生研究院生物样本库（NIH BioLINCC）的数据和血浆样本，我们纳入了1577例急性呼吸窘迫综合征患者组成队列，这些患者来自两项先前完成的临床试验EDEN和SAILS。我们使用市售酶联免疫吸附测定试剂盒（R&D Systems）在插管后24小时内测量血浆中的PCSK9水平。我们使用Cox比例风险模型评估PCSK9与死亡率的相关性。我们还评估了与PCSK9水平相关的临床因素，以及PCSK9与无机械通气天数和无ICU护理天数的相关性。
结果
在1577例ARDS患者中，中位年龄为53岁（四分位间距42 - 65岁），中位急性生理与慢性健康状况评分系统III（APACHE III）评分为91分（72 - 111分），表明为中度危重病。PCSK9水平为339.3 ng/mL（四分位间距248.0 - 481.0）。在多变量模型中，种族、ARDS病因、体重指数、既往肝病、体温、钠、白细胞计数和血小板计数与PCSK9水平相关。脓毒症的存在、血管加压药的使用和呼吸机参数与PCSK9水平无关。PCSK9水平与院内死亡率无关（每四分位间距的风险比为0.96，95%置信区间为0.84 - 1.08，P = 0.47）。较高的PCSK9水平与更少的无ICU天数和无呼吸机天数相关。
结论
血浆PCSK9与ARDS患者的死亡率无关，然而较高的PCSK9水平与较少的无ICU天数和无呼吸机天数等次要结局相关。ARDS中与PCSK9相关的临床因素在很大程度上是不可改变的。有必要进一步研究以明确这种关联的机制。
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