Stelmach Iwona, Zaczeniuk Magdalena, Sztafińska Anna, Majak Paweł, Jerzyńska Joanna, Kuklinska-Pijanka Anna, Stelmach Wlodzimierz
Department of Pediatrics and Allergy, Medical University of Lodz, Lodz, Poland.
Allergy Asthma Proc. 2016 Sep;37(5):84-92. doi: 10.2500/aap.2016.37.3974.
The pathogenesis of exercise-induced bronchoconstriction (EIB) is poorly understood.
To evaluate the biomarkers concentration in exhaled breath condensate (EBC) in schoolchildren with postexercise symptoms. We also evaluated changes in fractional exhaled nitric oxide (FeNO) value and the serum tryptase level after exercise.
One hundred children with postexercise symptoms were included. Methacholine challenge testing (MCT) was performed at visit 2, and exercise challenge testing (ECT) was performed at visit 3. Before and after ECT serum tryptase levels and FeNO values were measured. EBC was collected after ECT from 10 randomly selected children from each group. The children were assigned to the following groups: ECT(+) MCT(+), ECT(+) MCT(-), ECT(-) MCT(+), ECT(-) MC(-). We measured the following molecules: eotaxin, interleukin (IL) 8, IL-1ra, IL-1 beta, IL-6, IL-1 alpha, IL-12(p40), IL-5, granulocyte-macrophage colony-stimulating factor, IL-7, IL-15, IL-4, IL-2, IL-10, tumor necrosis factor alpha, interferon gamma, IL-13, tumor necrosis factor beta, monocyte chemoattractant protein-1, IL-17A, macrophage inflammatory proteins-1 alpha, macrophage inflammatory proteins-1 beta, IL-12(p70), and regulated on activation, normal T-cell expressed and secreted by using a multiplex immunoassay. Prostaglandin E2 (PGE2), leukotriene B4, and cysteinyl leukotriene were analyzed by using separate enzyme-linked immunosorbent assay kits.
In the MCT(+) group, a detectable level of IL4 in EBC and detectible levels of eicosanoids were seen in the ECT(+) group. We observed the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations in patients with detectable compared with patients without detectable levels of cytokines in EBC. We showed ECT-induced reduction in the tryptase level in patients with a nondetectable PGE2 level in EBC and an increase in tryptase levels in patients who had detectable levels of PGE2 in EBC.
EBC was a useful method to estimate inflammation but only in children with symptoms and with EIB shown by a positive ECT. Children with a positive ECT had detectable levels of eicosanoids in EBC; the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations was observed. The results of above study confirm the role of mast cells and eicosanoids in the pathogenesis of EIB in children.
运动诱发性支气管收缩(EIB)的发病机制尚不清楚。
评估有运动后症状的学龄儿童呼出气冷凝液(EBC)中生物标志物的浓度。我们还评估了运动后呼出气一氧化氮分数(FeNO)值和血清类胰蛋白酶水平的变化。
纳入100名有运动后症状的儿童。在第2次就诊时进行乙酰甲胆碱激发试验(MCT),在第3次就诊时进行运动激发试验(ECT)。在ECT前后测量血清类胰蛋白酶水平和FeNO值。从每组中随机选择10名儿童在ECT后收集EBC。将儿童分为以下几组:ECT(+)MCT(+)、ECT(+)MCT(-)、ECT(-)MCT(+)、ECT(-)MCT(-)。我们测量了以下分子:嗜酸性粒细胞趋化因子、白细胞介素(IL)-8、IL-1受体拮抗剂、IL-1β、IL-6、IL-1α、IL-12(p40)、IL-5、粒细胞-巨噬细胞集落刺激因子、IL-7、IL-15、IL-4、IL-2、IL-10、肿瘤坏死因子α、干扰素γ、IL-13、肿瘤坏死因子β、单核细胞趋化蛋白-1、IL-17A、巨噬细胞炎性蛋白-1α、巨噬细胞炎性蛋白-1β、IL-12(p70),以及通过多重免疫测定法检测的活化正常T细胞表达和分泌的调节因子。使用单独的酶联免疫吸附测定试剂盒分析前列腺素E2(PGE2)、白三烯B4和半胱氨酰白三烯。
在MCT(+)组中,EBC中可检测到IL4水平,在ECT(+)组中可检测到类花生酸水平。我们观察到,与EBC中细胞因子水平不可检测的患者相比,EBC中细胞因子水平可检测的患者中,ECT诱导的FeNO和血清类胰蛋白酶浓度变化方向相反。我们发现,EBC中PGE2水平不可检测的患者,ECT后类胰蛋白酶水平降低;EBC中PGE2水平可检测的患者,ECT后类胰蛋白酶水平升高。
EBC是评估炎症的一种有用方法,但仅适用于有症状且ECT呈阳性显示患有EIB 的儿童。ECT呈阳性的儿童EBC中可检测到类花生酸水平;观察到ECT诱导的FeNO和血清类胰蛋白酶浓度变化方向相反。上述研究结果证实了肥大细胞和类花生酸在儿童EIB发病机制中的作用。