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哮喘患儿与健康对照者呼出气中类二十烷酸谱分析。

Exhaled eicosanoid profiles in children with atopic asthma and healthy controls.

机构信息

University Children Hospital, Kraków, ul. Wielicka, Poland.

出版信息

Pediatr Pulmonol. 2013 Apr;48(4):324-35. doi: 10.1002/ppul.22615. Epub 2012 Jul 10.

Abstract

RATIONALE

Chronic endobronchial inflammation is a hallmark of pediatric asthma and involves the arachidonic acid pathway. Its non-volatile metabolites can be quantified in the exhaled breath condensate (EBC), and single substances have been studied as non-invasive biomarkers for the diagnosis and monitoring of children with asthma. The aim of this study was to compare the content and profile of a wider range of eicosanoids in the EBC between patients and a control group.

MATERIALS AND METHODS

EBC was sampled from 33 children (aged 12.4 ± 3.1 years) with stable atopic asthma (26 on inhaled steroid treatment) and 25 healthy controls (11.8 ± 3.2 years). Validated high performance liquid chromatography coupled with a tandem mass spectrometry platform (HPLC-MS2 ) was used to measure 13 different compounds. In addition, exhaled nitric oxide levels (FeNO) were measured and bronchial hyperresponsiveness (BHR) was assessed by an exercise challenge test in all subjects. An analytical approach was used for multivariate regression modeling of disease status using the most relevant variables.

RESULTS

The levels of PGEM (P < 0.001), PGD2 (P < 0.001), 6keto-PGF1α (P = 0.03), LTC4 (P < 0.001), trans-LTC4 (P = 0.04), and 5HETE (P = 0.02) were significantly higher in asthmatics compared to healthy children, while 11-dehydro TXB2 was significantly less abundant (P = 0.02). The eicosanoids asthma classification ratio (EACR) was computed as the logistic regression function using four variables: PGEM, PGD2, LTC4, and 5HETE. This composite parameter discriminated asthmatic from healthy children better than FEV1, FeNO, or BHR.

CONCLUSION

Complementary measurements of PGEM, PGD2, LTC4, and 5HETE in small-volume EBC samples are feasible by HPLC-MS2 and showed a specific profile in our study population. EACR should be evaluated further in the context of diagnosing and monitoring childhood asthma.

摘要

背景

慢性气道炎症是小儿哮喘的一个标志,涉及花生四烯酸途径。其非挥发性代谢物可在呼出气冷凝物(EBC)中定量,并已对单一物质进行了研究,作为诊断和监测哮喘儿童的非侵入性生物标志物。本研究旨在比较哮喘患者和对照组 EBC 中更广泛范围的类二十烷酸含量和谱。

材料和方法

从 33 名患有稳定特应性哮喘(26 名接受吸入性类固醇治疗)的儿童(年龄 12.4 ± 3.1 岁)和 25 名健康对照者(11.8 ± 3.2 岁)中采集 EBC 样本。使用经过验证的高效液相色谱-串联质谱联用平台(HPLC-MS2)测量 13 种不同的化合物。此外,所有受试者均测量呼气一氧化氮水平(FeNO)并通过运动挑战试验评估支气管高反应性(BHR)。使用最相关的变量,采用多元回归分析模型对疾病状态进行分析。

结果

与健康儿童相比,PGEM(P<0.001)、PGD2(P<0.001)、6keto-PGF1α(P=0.03)、LTC4(P<0.001)、trans-LTC4(P=0.04)和 5HETE(P=0.02)的水平在哮喘患者中明显升高,而 11-脱氢 TXB2 的含量明显降低(P=0.02)。使用四个变量(PGEM、PGD2、LTC4 和 5HETE),计算出类二十烷酸哮喘分类比(EACR)作为逻辑回归函数。与 FEV1、FeNO 或 BHR 相比,该复合参数能更好地区分哮喘患者和健康儿童。

结论

通过 HPLC-MS2 对小体积 EBC 样本中的 PGEM、PGD2、LTC4 和 5HETE 进行补充测量是可行的,并且在我们的研究人群中显示出特定的谱。应在诊断和监测儿童哮喘的背景下进一步评估 EACR。

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