Chiu Li-Chung, Lo Chi-Jen, Fan Chun-Ming, Tang Hsiang-Yu, Chan Tien-Ming, Ko How-Wen, Kuo Scott Chih-Hsi, Hsu Ping-Chih, Lee Chung-Shu, Lin Yu-Jr, Kao Kuo-Chin, Chuang Li-Pang, Hu Han-Chung, Cheng Mei-Ling
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Eur J Med Res. 2025 Sep 2;30(1):833. doi: 10.1186/s40001-025-03043-y.
Phenylalanine accumulation is associated with inflammation, immune system activation, and oxidative stress-all of which are involved in the pathophysiology of acute respiratory distress syndrome (ARDS). This study evaluated the correlation between longitudinal changes in plasma phenylalanine levels and clinical outcomes in patients with ARDS.
This prospective observational cohort study conducted in Taiwan focused on plasma amino acid profiling in ARDS patients between February 2017 and June 2018, and again between November 2021 and October 2023. Serial changes in plasma amino acid levels and clinical variables measured at days 1, 3, and 7 after ARDS onset were compared with clinical outcomes.
This study included 214 ICU patients, including 180 patients with ARDS and 34 patients without. Among ARDS patients, the in-hospital mortality rate was 45%. Plasma phenylalanine levels were significantly higher among ARDS patients than among ICU controls at all timepoints (days 1, 3, and 7). Plasma phenylalanine levels and phenylalanine/tyrosine ratios were significantly higher among non-survivors than among ARDS survivors throughout the observation period (all p < 0.05). ARDS patients with high plasma phenylalanine levels (> 125.3 µM; 47 patients; 26.1%) presented a significantly elevated risk of organ failure (i.e., higher APACHE II and SOFA scores) as well as 28-, 60-, 90-day, and all-cause hospital mortality, compared to those with low plasma phenylalanine levels (≤ 125.3 µM; 133 patients; 73.9%) (all p < 0.05). Multivariable logistic regression analysis revealed that plasma phenylalanine levels and phenylalanine/tyrosine ratios at day 1 were independently associated with hospital mortality (adjusted OR 1.009, [95% CI 1.001-1.017], p = 0.037 and adjusted OR 2.851, [95% CI 1.045-7.780], p = 0.041, respectively). A plasma phenylalanine level of > 125.3 µM had the highest predictive value for in-hospital mortality (adjusted OR 4.825, [95% CI 1.324-17.583], p = 0.017).
Plasma phenylalanine at the onset of ARDS is independently associated with hospital mortality. These findings indicate that phenylalanine metabolism may be disrupted early in the course of ARDS. They also indicate that plasma phenylalanine levels could serve as an early prognostic metabolic biomarker and potential therapeutic target.
苯丙氨酸蓄积与炎症、免疫系统激活和氧化应激相关，而这些均参与急性呼吸窘迫综合征（ARDS）的病理生理过程。本研究评估了ARDS患者血浆苯丙氨酸水平的纵向变化与临床结局之间的相关性。
这项前瞻性观察性队列研究在台湾进行，聚焦于2017年2月至2018年6月以及2021年11月至2023年10月期间ARDS患者的血浆氨基酸谱分析。将ARDS发病后第1、3和7天测得的血浆氨基酸水平和临床变量的系列变化与临床结局进行比较。
本研究纳入了214名ICU患者，其中包括180名ARDS患者和34名非ARDS患者。在ARDS患者中，院内死亡率为45%。在所有时间点（第1、3和7天），ARDS患者的血浆苯丙氨酸水平均显著高于ICU对照组。在整个观察期内，非幸存者的血浆苯丙氨酸水平和苯丙氨酸/酪氨酸比值均显著高于ARDS幸存者（所有p<0.05）。与血浆苯丙氨酸水平低（≤125.3µM；133例患者；73.9%）的患者相比，血浆苯丙氨酸水平高（>125.3µM；47例患者；26.1%）的ARDS患者发生器官衰竭的风险显著升高（即APACHE II和SOFA评分更高），以及28天、60天、90天和全因住院死亡率更高（所有p<0.05）。多变量逻辑回归分析显示，第1天的血浆苯丙氨酸水平和苯丙氨酸/酪氨酸比值与住院死亡率独立相关（调整后的OR分别为1.009，[95%CI 1.001-1.017]，p=0.037和调整后的OR 2.851，[95%CI 1.045-7.780]，p=0.041）。血浆苯丙氨酸水平>125.3µM对院内死亡率具有最高的预测价值（调整后的OR 4.825，[95%CI 1.324-17.583]，p=0.017）。
ARDS发病时的血浆苯丙氨酸与住院死亡率独立相关。这些发现表明，苯丙氨酸代谢可能在ARDS病程早期就受到破坏。它们还表明，血浆苯丙氨酸水平可作为早期预后代谢生物标志物和潜在治疗靶点。
