How does airway inflammation modulate asthmatic airway constriction? An antigen challenge study.
How does airway inflammation modulate asthmatic airway constriction? An antigen challenge study.
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气道炎症如何调节哮喘气道收缩？
DOI：
10.1152/japplphysiol.00075.2003
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Lutchen,KR
中科院分区：
文献类型：
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作者：
Henderson,AC;Ingenito,EP;Atileh,H;Israel,E;Suki,B;Lutchen,KR
在对吸入过敏原的晚期（LP）反应期间，来自嗜中性粒细胞和嗜酸性粒细胞的介质在气道内释放，类似于哮喘发作期间发生的情况。我们比较了阻塞的分布和可逆性的程度，以下深吸气（DI）在早期（EP）和LP反应在9个哮喘受试者与过敏原的挑战。通过测定动态肺阻力和弹性的频率依赖性，通过跟踪DI期间的气道阻力测定气道口径，以及通过测量激发后诱导痰中的炎性细胞测定气道炎症，来测定收缩的异质性。尽管基线时痰中嗜酸性粒细胞较少（<1%的非鳞状细胞），但哮喘受试者表现出明显的EP反应，伴有高度不均匀的收缩和最大限度扩张气道的能力降低。LP与所有受试者的大量气道炎症相关。然而，5名受试者仅表现出轻度LP收缩，而4名受试者表现出更明显的LP收缩，其特征在于类似于EP的异质收缩。 给予支气管扩张剂可完全缓解LP期间的支气管收缩。这些发现，连同DI期间支气管扩张反应受损，表明哮喘在平滑肌水平的生理异常，并表明哮喘的气道炎症与高度不均匀的收缩模式相关。这些数据支持哮喘受试者中反应性的变异性来自平滑肌对炎症反应的内在差异的假设。
During the late-phase (LP) response to inhaled allergen, mediators from neutrophils and eosinophils are released within the airways, resembling what occurs during an asthma attack. We compared the distribution of obstruction and degree of reversibility that follows a deep inspiration (DI) during early-phase (EP) and LP responses in nine asthmatic subjects challenged with allergen. Heterogeneity of constriction was assayed by determining frequency dependence of dynamic lung resistance and elastance, airway caliber by tracking airway resistance during a DI, and airway inflammation by measuring inflammatory cells in induced sputum postchallenge. Despite a paucity of eosinophils in the sputum at baseline (<1% of nonsquamous cells), asthmatic subjects showed a substantial EP response with highly heterogeneous constriction and reduced capacity to maximally dilate airways. The LP was associated with substantial airway inflammation in all subjects. However, five subjects showed only mild LP constriction, whereas four showed more marked LP constriction characterized by heterogeneous constriction similar to EP. Bronchoconstriction during LP was fully alleviated by administration of a bronchodilator. These findings, together with the impaired bronchodilatory response during a DI, indicate a physiological abnormality in asthma at the smooth muscle level and indicate that airway inflammation in asthma is associated with a highly nonuniform pattern of constriction. These data support the hypothesis that variability in responsiveness among asthmatic subjects derives from intrinsic differences in smooth muscle response to inflammation.