Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
J Allergy Clin Immunol. 2013 Sep;132(3):547-553. doi: 10.1016/j.jaci.2013.01.058. Epub 2013 Apr 19.
The relationship between anti-inflammatory lipoxins and proinflammatory leukotrienes might be important in the pathobiology and severity of asthma.
We sought to investigate whether exhaled breath condensate (EBC) lipoxin and leukotriene measurements can noninvasively characterize the asthmatic diathesis and its severity.
We measured lipoxin A4 (LXA4) and leukotriene B4 (LTB4) levels in EBC collected from patients with asthma of different severities and from healthy control subjects.
EBC LXA4 and LTB4 levels are increased in asthmatic patients compared with those seen in healthy control subjects (LXA4: 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 LXA4/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 LXA4 levels correlate with the degree of airflow obstruction measured by using FEV1 (r = 0.28, P = .018). An LXA4 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).
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.
抗炎型脂氧素与促炎型白三烯之间的关系可能在哮喘的病理生理学和严重程度中起着重要作用。
我们旨在研究呼出气冷凝液(EBC)中脂氧素和白三烯的测量能否无创地描述哮喘的体质及其严重程度。
我们测量了不同严重程度的哮喘患者和健康对照者的 EBC 中脂氧素 A4(LXA4)和白三烯 B4(LTB4)的水平。
与健康对照组相比,哮喘患者的 EBC LXA4 和 LTB4 水平升高(LXA4:分别为 31.40 与 2.41 pg/mL EBC,P <.001;LTB4:分别为 45.62 与 3.82 pg/mL EBC,P <.001)。尽管两种类二十烷酸的水平均在哮喘患者中升高,但 LXA4/LTB4 比值随哮喘严重程度的增加而降低。在重度哮喘患者中,该比值比中度哮喘患者低 41%(0.52 比 0.88,P =.034)。EBC LXA4 水平与使用 FEV1 测量的气流阻塞程度相关(r = 0.28,P =.018)。EBC LXA4 截断值为 7 pg/mL 时,对哮喘的诊断具有 90%的敏感性和 92%的特异性(曲线下面积,0.96;P <.001)。EBC LTB4 截断值为 11 pg/mL 时,对哮喘的诊断具有 100%的敏感性和 100%的特异性(曲线下面积,1;P <.001)。
所有哮喘患者的气道中均产生促炎和抗炎型类二十烷酸。随着哮喘严重程度的增加,促炎化合物的比例下降。这些发现支持使用 EBC 类二十烷酸测量进行哮喘的无创诊断,并表明严重哮喘患者的促分解代谢型类二十烷酸途径失调。