Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan.
Clin Exp Allergy. 2011 Dec;41(12):1711-8. doi: 10.1111/j.1365-2222.2011.03839.x. Epub 2011 Aug 22.
Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A(4) (LXA(4)) and the 15-epimer of LXA(4) (15-epi-LXA(4)) in relation to asthma severity in AIA subjects.
The purpose of this study is to estimate urinary LXA(4) and the 15-epimer concentrations to investigate lipoxins in AIA.
In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA(4), 15-epi-LXA(4) and leukotriene E(4) (LTE(4) ) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography.
The urinary LXA(4) concentration was significantly lower than the 15-epi-LXA(4) concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA(4) (P < 0.01) and higher urinary LTE(4) concentrations (P < 0.05) than the ATA group. Comparison of 15-epi-LXA(4) concentrations between the severe asthmatic and non-severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15-epi-LXA(4) concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE(4) to 15-epi-LXA(4) was superior to 15-epi-LXA(4) concentration and LTE(4) concentration as a predictive factor for aspirin intolerance.
We have demonstrated for the first time that urinary 15-epi-LXA(4) concentration is significantly higher than LXA(4) concentration in both the AIA and ATA groups. 15-Epi-LXA(4) concentration was significantly lower in the AIA group with an increased urinary LTE(4) concentration than in the ATA group. An imbalance between proinflammatory cysteinyl-leukotrienes and anti-inflammatory 15-epi-LXA(4) may be involved in AIA pathogenesis.
尽管花生四烯酸代谢异常可能是导致阿司匹林不耐受性哮喘（AIA）的原因，但关于 AIA 患者哮喘严重程度与尿中环内脂素 A（LXA（4））和 LXA（4）的 15-差向异构体（15-epi-LXA（4））浓度之间的关系知之甚少。
本研究旨在评估尿中 LXA（4）和 15-差向异构体的浓度，以研究 AIA 中的脂氧素。
在这项研究中，我们检查了 AIA、阿司匹林耐受型哮喘（ATA）和健康对照组。AIA 和 ATA 组进一步分为严重哮喘和非严重哮喘亚组。使用高效液相色谱法分离这些化合物后，使用酶免疫分析法定量测定尿中环内脂素 A（4）、15-差向异构体（15-epi-LXA（4））和白三烯 E（4）（LTE（4））。
哮喘患者的尿中环内脂素 A（4）浓度明显低于 15-差向异构体浓度。与 ATA 组相比，AIA 组尿 15-差向异构体（P<0.01）和 LTE（4）浓度明显升高（P<0.05）。AIA 和 ATA 组中严重哮喘和非严重哮喘患者的 15-差向异构体浓度比较表明，降低的 15-差向异构体浓度可能与阿司匹林不耐受有关，但与哮喘严重程度无关。受试者工作特征曲线表明，LTE（4）与 15-差向异构体浓度的比值优于 15-差向异构体浓度和 LTE（4）浓度作为预测阿司匹林不耐受的指标。
我们首次证明，AIA 和 ATA 两组患者的尿 15-差向异构体浓度均明显高于 LXA（4）浓度。与 ATA 组相比，AIA 组尿 LTE（4）浓度升高，15-差向异构体浓度显著降低。促炎半胱氨酰白三烯与抗炎 15-差向异构体之间的不平衡可能参与了 AIA 的发病机制。
