Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
J Intern Med. 2019 Jul;286(1):75-87. doi: 10.1111/joim.12891. Epub 2019 Mar 14.
A previous study found community-acquired pneumonia (CAP) patients with imbalance of high inflammation and discordantly low cortisol levels to benefit most from adjunctive corticosteroid treatment. Our aim was to validate this hypothesis in a preplanned secondary analysis of the randomized controlled STEP trial.
Patients included in the STEP trial receiving 50 mg prednisone or placebo for 5 days were categorized based on pro-inflammatory cytokines (Interleukin-6/8/MCP-1), CRP and cortisol levels on admission into four groups (high/low inflammation and high/low cortisol). The primary combined end-point was mortality or ICU admission within 30 days.
In total, 632 patients (315 prednisone, 317 placebo) were included in this analysis. Prednisone did not significantly reduce the risk for the primary end-point in patients with high cytokines/low cortisol and in any other subgroups. However, we noted some differences in the strength of corticosteroid effect in the different subgroups with stronger effects in patients with high cytokines [OR 0.44 (0.10,1.72)] compared to patients with low cytokines [OR 0.68 (0.30,1.5)] (P-interaction = 0.600). The effects did not differ according to cortisol levels.
The imbalance of high inflammation state and low cortisol levels did not predict treatment response to corticosteroids in patients with CAP. However, in line to previous research, inflammation as measured by cytokine levels irrespective of cortisol tended to predict treatment response to corticosteroids in CAP. Whether this concept may help to personalize corticosteroids to patients most likely benefitting from this treatment needs to be tested in future intervention trials.
先前的一项研究发现，患有高炎症失衡和皮质醇水平明显降低的社区获得性肺炎（CAP）患者从辅助皮质类固醇治疗中获益最大。我们的目的是在 STEP 试验的一项预先计划的二次分析中验证这一假设。
STEP 试验中接受 50mg 泼尼松龙或安慰剂治疗 5 天的患者根据入院时的促炎细胞因子（白细胞介素 6/8/MCP-1）、CRP 和皮质醇水平分为四组（高/低炎症和高/低皮质醇）。主要联合终点为 30 天内死亡或入住 ICU。
共纳入 632 例患者（泼尼松龙组 315 例，安慰剂组 317 例）进行本分析。泼尼松龙治疗并未显著降低高细胞因子/低皮质醇患者和任何其他亚组患者的主要终点风险。然而，我们在不同亚组中观察到皮质类固醇作用强度的一些差异，高细胞因子患者的作用更强[OR 0.44（0.10，1.72）]，而低细胞因子患者的作用较弱[OR 0.68（0.30，1.5）]（P 交互=0.600）。皮质醇水平不同，效果无差异。
高炎症状态和低皮质醇水平的失衡并不能预测 CAP 患者对皮质类固醇的治疗反应。然而，与先前的研究一致，无论皮质醇水平如何，细胞因子水平所测量的炎症倾向于预测 CAP 患者对皮质类固醇的治疗反应。这一概念是否可以帮助将皮质类固醇个体化应用于最有可能从中获益的患者，需要在未来的干预试验中进行检验。
