Hallstrand Teal S, Moody Mark W, Wurfel Mark M, Schwartz Lawrence B, Henderson William R, Aitken Moira L
Department of Medicine, Division of Pulmonary and Critical Care, University of Washington, Seattle, Washington 98195-6522, USA.
Am J Respir Crit Care Med. 2005 Sep 15;172(6):679-86. doi: 10.1164/rccm.200412-1667OC. Epub 2005 Jun 9.
Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of EIB differ regarding the inflammatory basis of this condition.
Our goals were to establish whether epithelial cell and mast cell activation with release of inflammatory mediators occurs during EIB and how histamine and cysteinyl leukotriene antagonists alter the airway events occurring during EIB.
Induced sputum was used to measure mast cell mediators and eicosanoids at baseline and 30 minutes after exercise challenge in 25 individuals with asthma with EIB. In a randomized, double-blind crossover study, the cysteinyl leukotriene antagonist montelukast and antihistamine loratadine or two matched placebos were administered for two doses before exercise challenge.
The percentage of columnar epithelial cells in induced sputum at baseline was associated with the severity of EIB. After exercise challenge, histamine, tryptase, and cysteinyl leukotrienes significantly increased and prostaglandin E(2) and thromboxane B(2) significantly decreased in the airways, and there was an increase in columnar epithelial cells in the airways. The concentration of columnar epithelial cells was associated with the levels of histamine and cysteinyl leukotrienes in the airways. Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine into the airways, but did not inhibit the release of columnar epithelial cells into the airways.
These data indicate that epithelial cells, mast cell mediators, and eicosanoids are released into the airways during EIB, supporting an inflammatory basis for EIB.
运动诱发性支气管收缩（EIB）是一种非常普遍的病症，其发病机制尚不清楚。关于EIB发病机制的两种相互竞争的理论在这种病症的炎症基础方面存在差异。
我们的目标是确定在EIB期间是否发生上皮细胞和肥大细胞激活并释放炎症介质，以及组胺和半胱氨酰白三烯拮抗剂如何改变EIB期间发生的气道事件。
在25名患有EIB的哮喘患者中，使用诱导痰在运动激发前的基线和激发后30分钟测量肥大细胞介质和类花生酸。在一项随机、双盲交叉研究中，在运动激发前给予两剂半胱氨酰白三烯拮抗剂孟鲁司特和抗组胺药氯雷他定或两种匹配的安慰剂。
基线时诱导痰中柱状上皮细胞的百分比与EIB的严重程度相关。运动激发后，气道中的组胺、类胰蛋白酶和半胱氨酰白三烯显著增加，前列腺素E2和血栓素B2显著降低，气道中的柱状上皮细胞增加。柱状上皮细胞的浓度与气道中组胺和半胱氨酰白三烯水平相关。孟鲁司特和氯雷他定治疗可抑制半胱氨酰白三烯和组胺释放到气道中，但不抑制柱状上皮细胞释放到气道中。
这些数据表明，在EIB期间上皮细胞、肥大细胞介质和类花生酸释放到气道中，支持EIB存在炎症基础。
