Evans D J, Coulby L J, O'Connor B J
Clinical Studies Unit, Royal Brompton Hospital, London, UK.
Thorax. 1996 Dec;51(12):1185-91. doi: 10.1136/thx.51.12.1185.
Airway responsiveness to histamine and methacholine, direct smooth muscle spasmogens, is increased following inhalation of allergen. Although the aetiology of this phenomenon is unclear, increased cellular or neural activity may be involved since allergen also induces increases in airway responsiveness to the mast cell stimulus adenosine-5'-monophosphate (AMP) and the neural stimulus bradykinin.
To explore this further, the airway responsiveness to sodium metabisulphite (MBS), an indirect neural stimulus with similar characteristics to bradykinin, was compared in 18 mild steroid-naive asthmatic subjects with the airway responsiveness to histamine before and after allergen challenge with extracts of house dust mite, grass pollen, or cat. All subjects inhaled doubling increments of histamine and MBS until the concentration provoking a 20% fall in forced expiratory volume in one second (PC20) was reached before and three hours after allergen challenge. Twelve of the subjects had additional challenges at 24 hours after the allergen.
Following allergen challenge all subjects showed an early response and 14 also had a late asthmatic response. For histamine there was a significant increase in airway responsiveness at both three and 24 hours compared with values before the allergen (0.89 (0.25) and 1.53 (0.52) doubling dose changes, respectively). In contrast, airway responsiveness to MBS was unaltered by allergen challenge (0.29 (0.27) and -0.33 (0.28) doubling dose changes compared with pre-allergen values at three and 24 hours, respectively).
These data suggest that activation of airway sensory nerves is unlikely to contribute to the increase in airway responsiveness following inhalation of allergen. The previously observed allergen induced increase in airway responsiveness to bradykinin and AMP may involve non-neural pathways.
吸入变应原后,气道对组胺和乙酰甲胆碱(直接作用于平滑肌的致痉剂)的反应性会增强。尽管这一现象的病因尚不清楚,但细胞或神经活动的增加可能与之有关,因为变应原也会导致气道对肥大细胞刺激物5'-单磷酸腺苷(AMP)和神经刺激物缓激肽的反应性增强。
为进一步探究此问题,在18名未使用过类固醇的轻度哮喘患者中,比较了在经屋尘螨、草花粉或猫提取物进行变应原激发前后,气道对偏亚硫酸氢钠(MBS,一种与缓激肽特性相似的间接神经刺激物)的反应性与对组胺的反应性。所有受试者在变应原激发前及激发后3小时吸入组胺和MBS浓度成倍增加的气雾剂,直至达到引起一秒用力呼气量下降20%的浓度(PC20)。其中12名受试者在变应原激发后24小时还进行了额外的激发试验。
变应原激发后,所有受试者均出现早期反应,14名受试者还出现了迟发性哮喘反应。对于组胺,与变应原激发前相比,3小时和24小时时气道反应性均显著增加(分别为0.89(0.25)和1.53(0.52)倍剂量变化)。相比之下,变应原激发并未改变气道对MBS的反应性(3小时和24小时时与变应原激发前相比,分别为0.29(0.27)和 -0.33(0.28)倍剂量变化)。
这些数据表明,吸入变应原后气道反应性增加不太可能是由气道感觉神经激活所致。先前观察到的变应原诱导的气道对缓激肽和AMP反应性增加可能涉及非神经途径。