Acute respiratory distress syndrome (ARDS) involves dysregulated immune-inflammatory responses, characterized by severe oxidative stress and high mortality. Metabolites modulating the inflammatory and immune responses may play a central role in the pathogenesis of ARDS. Most biogenic amines may induce the production of reactive oxygen species, oxidative stress, mitochondrial dysfunction, and programmed cell death. We conducted a prospective study on metabolic profiling specific to the amino acids and biogenic amines of 69 patients with ARDS. Overall, hospital mortality was 52.2%. Between day 1 and day 7 after ARDS onset, plasma kynurenine levels and the kynurenine/tryptophan ratio were significantly higher among non-survivors than in survivors (all p < 0.05). Urine metabolic profiling revealed a significantly higher prevalence of tryptophan degradation and higher concentrations of metabolites downstream of the kynurenine pathway among non-survivors than among survivors upon ARDS onset. Cox regression models revealed that plasma kynurenine levels and the plasma kynurenine/tryptophan ratio on day 1 were independently associated with hospital mortality. The activation of the kynurenine pathway was associated with mortality in patients with ARDS. Metabolic phenotypes and modulating metabolic perturbations of the kynurenine pathway could perhaps serve as prognostic markers or as a target for therapeutic interventions aimed at reducing oxidative stress and mortality in ARDS.

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色氨酸代谢的犬尿氨酸途径与急性呼吸窘迫综合征患者的医院死亡率相关：一项前瞻性队列研究

急性呼吸窘迫综合征 (ARDS) 涉及失调的免疫炎症反应，其特点是严重的氧化应激和高死亡率。调节炎症和免疫反应的代谢物可能在 ARDS 的发病机制中发挥核心作用。大多数生物胺可能会导致活性氧的产生、氧化应激、线粒体功能障碍和程序性细胞死亡。我们对 69 名 ARDS 患者的氨基酸和生物胺特异性代谢谱进行了前瞻性研究。总体而言，住院死亡率为 52.2%。在 ARDS 发作后的第 1 天和第 7 天之间，非幸存者的血浆犬尿氨酸水平和犬尿氨酸/色氨酸比率显着高于幸存者（所有p< 0.05)。尿液代谢分析显示，与 ARDS 发作时的幸存者相比，非幸存者中色氨酸降解的发生率和犬尿氨酸通路下游代谢物浓度显着更高。Cox 回归模型显示，第 1 天的血浆犬尿氨酸水平和血浆犬尿氨酸/色氨酸比率与医院死亡率独立相关。犬尿氨酸通路的激活与 ARDS 患者的死亡率相关。代谢表型和调节犬尿氨酸途径的代谢扰动可能作为预后标志物或作为旨在减少 ARDS 氧化应激和死亡率的治疗干预的目标。