Exhaled breath condensate eicosanoid levels associate with asthma and its severity

Exhaled breath condensate eicosanoid levels associate with asthma and its severity
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DOI:
10.1016/j.jaci.2013.01.058
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发表时间:
2013-09-01
影响因子:
14.2
通讯作者:
Israel, Elliot
Israel, Elliot
中科院分区:
医学1区
文献类型:
--
作者:
Kazani, Shamsah;Planaguma, Anna;Israel, Elliot

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背景:抗炎性脂氧素和促炎性白三烯之间的关系可能在哮喘的病理学和严重程度中很重要。目的:我们试图研究呼出气冷凝物 (EBC) 脂氧素和白三烯测量是否可以无创地表征哮喘素质及其严重程度。方法:我们测量了 EBC 中的脂氧素 A(4) (LXA(4)) 和白三烯 B-4 (LTB4) 水平结果:与健康对照受试者相比,哮喘患者的 EBC LXA(4) 和 LTB4 水平升高(LXA(4):分别为 31.40 vs 2.41 pg/mL EBC [P < .001];LTB4:分别为 45.62 vs 3.82 pg/mL EBC [P < .001])。尽管哮喘患者中两种类二十烷酸的水平均升高,但 LXA(4)/LTB4 比率随着哮喘严重程度的增加而降低。重度哮喘患者比中度哮喘患者低 41%(0.52 vs 0.88,P = .034)。 EBC LXA(4) 水平与使用 FEV1 测量的气流阻塞程度相关(r = 0.28,P = .018)。 7 pg/mL EBC 的 LXA(4) 截止值可为哮喘诊断提供 90% 的敏感性和 92% 的特异性(曲线下面积,0.96;P < .001)。 LTB4 截止值为 11 pg/mL EBC,为哮喘诊断提供 100% 的敏感性和 100% 的特异性(曲线下面积,1;P < .001)。结论:所有哮喘患者的气道中都会产生促消退和促炎类二十烷酸。促缓解化合物的比例随着哮喘严重程度而降低。这些发现支持 EBC 类二十烷酸测量在哮喘无创诊断中的作用,并表明重度哮喘患者的促缓解类二十烷酸途径失调。
Background: The relationship between anti-inflammatory lipoxins and proinflammatory leukotrienes might be important in the pathobiology and severity of asthma.Objective: We sought to investigate whether exhaled breath condensate (EBC) lipoxin and leukotriene measurements can noninvasively characterize the asthmatic diathesis and its severity.Methods: We measured lipoxin A(4) (LXA(4)) and leukotriene B-4 (LTB4) levels in EBC collected from patients with asthma of different severities and from healthy control subjects.Results: EBC LXA(4) and LTB4 levels are increased in asthmatic patients compared with those seen in healthy control subjects (LXA(4): 31.40 vs 2.41 pg/mL EBC, respectively [P < .001]; LTB4: 45.62 vs 3.82 pg/mL EBC, respectively [P < .001]). Although levels of both eicosanoids are increased in asthmatic patients, the LXA(4)/LTB4 ratio decreases with increasing asthma severity. It is 41% lower in patients with severe versus moderate asthma (0.52 vs 0.88, P = .034). EBC LXA(4) levels correlate with the degree of airflow obstruction measured by using FEV1 (r = 0.28, P = .018). An LXA(4) cutoff value of 7 pg/mL EBC provides 90% sensitivity and 92% specificity for the diagnosis of asthma (area under the curve, 0.96; P < .001). An LTB4 cutoff value of 11 pg/mL EBC provides 100% sensitivity and 100% specificity for the diagnosis of asthma (area under the curve, 1; P < .001).Conclusions: Proresolving and proinflammatory eicosanoids are generated in the airways of all asthmatic patients. The proportion of proresolving compounds decreases with asthma severity. These findings support the role for EBC eicosanoid measurements in the noninvasive diagnosis of asthma and suggest that proresolving eicosanoid pathways are dysregulated in patients with severe asthma.