Centre for inflammation and Tissue Repair (CITR), University College London Division of Medicine, London, UK.
Department of Medicine, University of Cambridge, Cambridge, UK.
Thorax. 2024 Feb 15;79(3):227-235. doi: 10.1136/thorax-2023-220292.
Inflammatory 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.
Baseline 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.
Ferritin 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.
Ferritin 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.
在急性呼吸窘迫综合征（ARDS）中已经确定了炎症亚表型。脓毒症中的高血铁蛋白与过度炎症、更差的临床结局相关，并且可能预测免疫调节的获益。我们的目的是确定 ARDS 患者中升高的铁蛋白是否确定了一个亚表型。
在两项他汀类药物随机对照试验（Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction-2（HARP-2）；发现队列，英国和神经肌肉阻滞剂（ROSE；验证队列，美国）中测量了 ARDS 患者的基线血浆铁蛋白浓度。使用逻辑回归模型和限制立方样条进行分析，以确定与 28 天死亡率相关的铁蛋白阈值。
HARP-2 中有 511 名患者（纳入患者的 95%）和 ROSE 中有 847 名患者（纳入患者的 84%）测量了铁蛋白。铁蛋白在两项研究中均与 28 天死亡率一致，并且在荟萃分析后，铁蛋白的对数倍增加与 28 天死亡率的 OR 1.71（95%CI 1.01 至 2.90）相关。铁蛋白>1380ng/mL（HARP-2 为 28%，ROSE 为 24%）的患者在两项研究中均有更高的 28 天死亡率和更少的呼吸机无天数。包括混杂因素（急性生理学和慢性健康评估-II 评分和 ARDS 病因）的中介分析表明，白细胞介素（IL）-18 作为铁蛋白和死亡率之间的中间途径具有统计学意义。
铁蛋白是 ARDS 的一种有用的临床生物标志物，与患者结局较差相关。这些结果为针对该亚组患者的 IL-18 进行免疫调节药物的前瞻性干预试验提供了支持。
