血浆与尿液15-oxo-ETE可反应阿司匹林加重性呼吸道疾病患者疾病严重程度
2025/06/16
摘要
背景：阿司匹林加重性呼吸道疾病（Aspirin-exacerbated respiratory disease , AERD）患者在花生四烯酸（AA）代谢方面表现出促炎与抗炎类花生酸失衡的特征。本研究聚焦于15-脂氧合酶-1（15-LOX-1）与5-脂氧合酶（5-LOX）代谢通路的终末代谢产物。
目的：通过检测血浆与尿液中15-氧代-二十碳四烯酸（15-oxo-ETE）和5-氧代-二十碳四烯酸（5-oxo-ETE）的水平，结合其他脂氧合酶代谢产物和变量，识别可能存在的代谢组学聚类簇。
方法：对78例AERD患者和63例阿司匹林耐受型哮喘（Aspirin-tolerant asthma, ATA）患者，基于23项变量进行层次聚类分析。分析变量包括人口统计学信息、临床及生化指标、治疗数据、鼻窦CT结果，以及采用高效液相色谱串联质谱法（HPLC-MS/MS）检测的血浆和尿液中选定的类花生酸水平。
结果: 在AERD组和阿司匹林耐受型哮喘组中均识别出两个亚型（内表型）。与阿司匹林耐受型哮喘亚群相比，AERD亚群的鼻窦CT评分（Lund-Mackay评分）及尿液白三烯E4（LTE4）水平显著升高，而尿液15-oxo-ETE水平则显著降低。AERD亚群1和阿司匹林耐受型哮喘亚群1的患者（相比各自的亚群2）年龄更大、体重指数（BMI）更高、哮喘症状更重、控制更差，同时血浆中15-羟基二十碳四烯酸（15-HETE）、15-oxo-ETE和5-羟基二十碳四烯酸（5-HETE）水平更高。AERD患者相比阿司匹林耐受型哮喘患者，鼻窦病变更严重，尿液中15-oxo-ETE和LTE4水平也更高。
结论: 在AERD患者中，血浆15-oxo-ETE水平升高而尿液中该物质浓度降低，提示哮喘症状更严重，控制更困难，且患者年龄较大、BMI较高。
关键词：15-氧-二十碳四烯酸；阿司匹林加重性呼吸道疾病；聚类分析；类花生酸。
文献来源：（Szatkowski P, Stępień A, Ćmiel A, et al. Metabolomic endophenotypes based on oxo-eicosatetraenoic acids in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. Published online May 29, 2025.）
Abstract
Background: Arachidonic acid (AA) metabolism in patients with aspirin-exacerbated respiratory disease (AERD) is characterized by an imbalance between proinflammatory and anti-inflammatory eicosanoids. In this study, we focused on end metabolites of the 15-lipoxygenase-1 (15-LOX-1) and 5-lipoxygenase (5-LOX) pathways.
Objective: To identify possible metabolomic clusters based on plasma and urinary levels of 15-oxo-eicosatetraenoic acid (15-oxo-ETE) and 5-oxo-eicosatetraenoic acids (5-oxo-ETE) in combination with other lipoxygenase AA metabolites and variables.
Methods: Hierarchical cluster analysis was performed in 78 patients with AERD and in 63 patients with aspirin-tolerant asthma (ATA), both with 23 variables. These variables included demographic, clinical, biochemical, and treatment data, sinus computed tomography findings, and plasma and urinary levels of selected eicosanoids measured by high-performance liquid chromatography and tandem mass spectrometry.
Results: Two clusters (endophenotypes) were distinguished in each study group. The Lund-Mackay (LM) score on paranasal sinus computed tomography and urinary leukotriene E4 (LTE4) levels were significantly higher, while urinary 15-oxo-ETE levels were significantly lower, in AERD clusters compared with ATA clusters. Patients in cluster 1AERD (vs cluster 2AERD) and cluster 1ATA (vs cluster 2ATA) were older, had higher body mass index (BMI), more severe asthma and worse asthma control, as well as higher levels of plasma 15-hydroxyeicosatetraenoic acid, 15-oxo-ETE, and 5-hydroxyeicosatetraenoic acid. Patients with AERD had more advanced changes in the sinuses and higher urinary levels of 15-oxo-ETE and LTE4 than patients with ATA.
Conclusion: Higher plasma and lower urinary levels of 15-oxo-ETE are associated with more severe asthma and worse asthma control in patients with AERD with older age and higher BMI.
Keywords: 15-oxoeicosatetraenoic acid; aspirin-exacerbated respiratory disease; cluster analysis; eicosanoids.
背景：阿司匹林加重性呼吸道疾病（Aspirin-exacerbated respiratory disease , AERD）患者在花生四烯酸（AA）代谢方面表现出促炎与抗炎类花生酸失衡的特征。本研究聚焦于15-脂氧合酶-1（15-LOX-1）与5-脂氧合酶（5-LOX）代谢通路的终末代谢产物。
目的：通过检测血浆与尿液中15-氧代-二十碳四烯酸（15-oxo-ETE）和5-氧代-二十碳四烯酸（5-oxo-ETE）的水平，结合其他脂氧合酶代谢产物和变量，识别可能存在的代谢组学聚类簇。
方法：对78例AERD患者和63例阿司匹林耐受型哮喘（Aspirin-tolerant asthma, ATA）患者，基于23项变量进行层次聚类分析。分析变量包括人口统计学信息、临床及生化指标、治疗数据、鼻窦CT结果，以及采用高效液相色谱串联质谱法（HPLC-MS/MS）检测的血浆和尿液中选定的类花生酸水平。
结果: 在AERD组和阿司匹林耐受型哮喘组中均识别出两个亚型（内表型）。与阿司匹林耐受型哮喘亚群相比，AERD亚群的鼻窦CT评分（Lund-Mackay评分）及尿液白三烯E4（LTE4）水平显著升高，而尿液15-oxo-ETE水平则显著降低。AERD亚群1和阿司匹林耐受型哮喘亚群1的患者（相比各自的亚群2）年龄更大、体重指数（BMI）更高、哮喘症状更重、控制更差，同时血浆中15-羟基二十碳四烯酸（15-HETE）、15-oxo-ETE和5-羟基二十碳四烯酸（5-HETE）水平更高。AERD患者相比阿司匹林耐受型哮喘患者，鼻窦病变更严重，尿液中15-oxo-ETE和LTE4水平也更高。
结论: 在AERD患者中，血浆15-oxo-ETE水平升高而尿液中该物质浓度降低，提示哮喘症状更严重，控制更困难，且患者年龄较大、BMI较高。
关键词：15-氧-二十碳四烯酸；阿司匹林加重性呼吸道疾病；聚类分析；类花生酸。
文献来源：（Szatkowski P, Stępień A, Ćmiel A, et al. Metabolomic endophenotypes based on oxo-eicosatetraenoic acids in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. Published online May 29, 2025.）
（南方医科大学南方医院 蓝益生 黄海伦 赵海金）
Abstract
Background: Arachidonic acid (AA) metabolism in patients with aspirin-exacerbated respiratory disease (AERD) is characterized by an imbalance between proinflammatory and anti-inflammatory eicosanoids. In this study, we focused on end metabolites of the 15-lipoxygenase-1 (15-LOX-1) and 5-lipoxygenase (5-LOX) pathways.
Objective: To identify possible metabolomic clusters based on plasma and urinary levels of 15-oxo-eicosatetraenoic acid (15-oxo-ETE) and 5-oxo-eicosatetraenoic acids (5-oxo-ETE) in combination with other lipoxygenase AA metabolites and variables.
Methods: Hierarchical cluster analysis was performed in 78 patients with AERD and in 63 patients with aspirin-tolerant asthma (ATA), both with 23 variables. These variables included demographic, clinical, biochemical, and treatment data, sinus computed tomography findings, and plasma and urinary levels of selected eicosanoids measured by high-performance liquid chromatography and tandem mass spectrometry.
Results: Two clusters (endophenotypes) were distinguished in each study group. The Lund-Mackay (LM) score on paranasal sinus computed tomography and urinary leukotriene E4 (LTE4) levels were significantly higher, while urinary 15-oxo-ETE levels were significantly lower, in AERD clusters compared with ATA clusters. Patients in cluster 1AERD (vs cluster 2AERD) and cluster 1ATA (vs cluster 2ATA) were older, had higher body mass index (BMI), more severe asthma and worse asthma control, as well as higher levels of plasma 15-hydroxyeicosatetraenoic acid, 15-oxo-ETE, and 5-hydroxyeicosatetraenoic acid. Patients with AERD had more advanced changes in the sinuses and higher urinary levels of 15-oxo-ETE and LTE4 than patients with ATA.
Conclusion: Higher plasma and lower urinary levels of 15-oxo-ETE are associated with more severe asthma and worse asthma control in patients with AERD with older age and higher BMI.
Keywords: 15-oxoeicosatetraenoic acid; aspirin-exacerbated respiratory disease; cluster analysis; eicosanoids.
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