Henderson A C, Ingenito E P, Atileh H, Israel E, Suki B, Lutchen K R
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
J Appl Physiol (1985). 2003 Aug;95(2):873-82; discussion 863. doi: 10.1152/japplphysiol.00075.2003. Epub 2003 Apr 18.
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.
在对吸入性变应原的迟发相（LP）反应中，中性粒细胞和嗜酸性粒细胞释放的介质在气道内被释放出来，类似于哮喘发作时的情况。我们比较了9名接受变应原激发的哮喘患者在早期相（EP）和LP反应期间深吸气（DI）后阻塞的分布情况以及可逆程度。通过测定动态肺阻力和弹性的频率依赖性来分析收缩的异质性，通过在DI期间追踪气道阻力来评估气道口径，通过测量激发后诱导痰中的炎症细胞来评估气道炎症。尽管基线时痰中嗜酸性粒细胞很少（<非鳞状细胞的1%），但哮喘患者表现出显著的EP反应，收缩高度异质性且最大程度扩张气道的能力降低。所有受试者的LP均与显著的气道炎症相关。然而，5名受试者仅表现出轻度的LP收缩，而4名受试者表现出更明显的LP收缩，其特征是与EP相似的异质性收缩。LP期间的支气管收缩通过给予支气管扩张剂可完全缓解。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存在生理异常，并表明哮喘中的气道炎症与高度不均匀的收缩模式相关。这些数据支持了这样一种假说，即哮喘患者反应性的变异性源于平滑肌对炎症反应的内在差异。
