Brown R H, Mitzner W
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
J Appl Physiol (1985). 1998 Dec;85(6):2012-7. doi: 10.1152/jappl.1998.85.6.2012.
A sine qua non of hyperresponsive airway disease in asthmatic subjects is the lack of a maximal response with increasing doses of aerosol agonist challenge. Normal subjects, however, often appear to exhibit an airway response plateau effect even when challenged with high concentrations of agonist. To investigate this question of maximal narrowing in individual airways in vivo, we used high-resolution computed tomography to visualize canine airways narrowed by two routes of agonist challenge. We compared airway narrowing induced by methacholine (MCh) via the conventional aerosol route to that caused by local atomization of MCh directly to individual airways. Our results showed that, with aerosol challenge, airway responses never reached a truly flat plateau even at the highest possible nebulizer concentrations. Airway closure was never observed. However, when MCh was delivered directly to the airway luminal surface, airways could be easily narrowed to complete closure at modest (10 mg/ml) agonist concentrations. Thus neither the elastic recoil of the lung nor limitations of smooth muscle shortening can be responsible for the apparent plateauing of dose-response curves. We suggest that the plateau results from limitations associated with the delivery of high concentration of agonists via the aerosol route.
哮喘患者气道高反应性疾病的一个必要条件是随着雾化激动剂剂量增加缺乏最大反应。然而，正常受试者即使在高浓度激动剂激发下，似乎也常常表现出气道反应平台效应。为了在体内研究单个气道最大狭窄的这个问题，我们使用高分辨率计算机断层扫描来可视化通过两种激动剂激发途径变窄的犬气道。我们将通过传统雾化途径给予的乙酰甲胆碱（MCh）诱导的气道狭窄与直接将MCh局部雾化到单个气道所引起的气道狭窄进行了比较。我们的结果表明，通过雾化激发，即使在最高可能的雾化器浓度下，气道反应也从未达到真正平坦的平台。从未观察到气道关闭。然而，当将MCh直接递送至气道管腔表面时，在适度的（10mg/ml）激动剂浓度下气道可容易地变窄至完全关闭。因此，肺的弹性回缩和平滑肌缩短的限制都不能解释剂量反应曲线明显的平台化。我们认为该平台是由通过雾化途径递送高浓度激动剂相关的限制导致的。
