Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)
Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)
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DOI：
10.1136/thorax-2023-220292
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发表时间：
2023-12-26
期刊：
影响因子：
10
通讯作者：
O'Kane，Cecilia M.
中科院分区：
文献类型：
--
作者：
Mehta，Puja;Samanta，Romit J.;O'Kane，Cecilia M.
研究背景急性呼吸窘迫综合征（ARDS）的炎症亚表型已被确定。脓毒症患者的高铁蛋白血症与炎症反应过度、临床结局较差相关，并可预测免疫调节的获益。我们的目的是确定是否提高铁蛋白确定一个subphenotype在患者ARDS.MethodsBaseline血浆铁蛋白浓度测定在两个随机对照试验的辛伐他汀（羟甲基戊二酰辅酶A还原酶抑制与辛伐他汀在急性肺损伤，以减少肺功能障碍-2（HARP-2），发现队列，英国）和神经肌肉阻滞（ROSE;验证队列，美国）与ARDS患者。结果进行了分析，使用逻辑回归模型与限制三次样条，以确定铁蛋白阈值与28天mortality.ResultsFerritin测定511例患者从HARP-2（95%的患者入组）和847例（84%的患者入组）从ROSE。在两项研究中，铁蛋白始终与28天死亡率相关，并且在荟萃分析后，铁蛋白对数倍增加与28天死亡率的OR 1.71（95% CI 1.01至2.90）相关。在两项研究中，铁蛋白>1380 ng/mL的患者（HARP-2 28%，ROSE 24%）的28天死亡率显著较高，无呼吸机天数较少。中介分析，包括混杂因素（急性生理和慢性健康评估-II评分和ARDS病因）表明，白细胞介素（IL）-18作为铁蛋白和mortality.ConclusionsFerritin之间的中间途径的统计学显着的贡献是一个临床有用的生物标志物在ARDS，并与更糟糕的患者预后。这些结果为靶向IL-18的免疫调节剂在高铁蛋白血症ARDS患者亚组中的前瞻性干预试验提供了支持。
BackgroundInflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was to determine if raised ferritin identified a subphenotype in patients with ARDS.MethodsBaseline plasma ferritin concentrations were measured in patients with ARDS from two randomised controlled trials of simvastatin (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction-2 (HARP-2); discovery cohort, UK) and neuromuscular blockade (ROSE; validation cohort, USA). Results were analysed using a logistic regression model with restricted cubic splines, to determine the ferritin threshold associated with 28-day mortality.ResultsFerritin was measured in 511 patients from HARP-2 (95% of patients enrolled) and 847 patients (84% of patients enrolled) from ROSE. Ferritin was consistently associated with 28-day mortality in both studies and following a meta-analysis, a log-fold increase in ferritin was associated with an OR 1.71 (95% CI 1.01 to 2.90) for 28-day mortality. Patients with ferritin >1380 ng/mL (HARP-2 28%, ROSE 24%) had a significantly higher 28-day mortality and fewer ventilator-free days in both studies. Mediation analysis, including confounders (acute physiology and chronic health evaluation-II score and ARDS aetiology) demonstrated a statistically significant contribution of interleukin (IL)-18 as an intermediate pathway between ferritin and mortality.ConclusionsFerritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.