Demnati R, Fraser R, Ghezzo H, Martin J G, Plaa G, Malo J L
Dept of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, Canada.
Eur Respir J. 1998 Apr;11(4):922-8. doi: 10.1183/09031936.98.11040922.
Reactive airways dysfunction syndrome (RADS) is an asthma-like condition that follows exposure to very high concentrations of an irritant material. We assessed the time-course of pathophysiological alterations in a model of RADS. Sprague-Dawley rats were exposed to 1,500 parts per million (ppm) of chlorine for 5 min. Lung resistance (RL), responsiveness to inhaled methacholine (MCh), the airway epithelium and bronchoalveolar lavage (BAL) were assessed over a 3 month period after exposure. RL increased significantly up to 3 days after exposure, reaching a maximal change of 110+/-16% from baseline. There was a significant decrease in the concentration of MCh required to increase RL by 0.20 cmH2O x mL(-1) x s from days 1-7 after exposure. In some rats, MCh hyperresponsiveness and RL changes persisted after exposure for as long as 1 and 3 months, respectively. Histological evaluation with morphometric evaluation revealed epithelial flattening, necrosis, increase in smooth muscle mass and evidence of epithelial regeneration. BAL showed an increased number of neutrophils. The timing of maximal abnormality in the appearance of the epithelium (days 1-3) corresponded to that of the maximal functional changes. Acute high chlorine exposure results in functional and pathological abnormalities that resolve in the majority of animals after a variable period; however, these changes can persist in some animals. Functional abnormalities in the initial stages may be related to airway epithelial damage.
反应性气道功能障碍综合征（RADS）是一种类似哮喘的病症，发生于接触高浓度刺激性物质之后。我们在RADS模型中评估了病理生理改变的时间进程。将斯普拉格-道利大鼠暴露于百万分之1500（ppm）的氯气中5分钟。在暴露后的3个月内评估肺阻力（RL）、对吸入乙酰甲胆碱（MCh）的反应性、气道上皮和支气管肺泡灌洗（BAL）情况。暴露后3天内RL显著增加，相对于基线的最大变化达到110±16%。暴露后第1 - 7天，使RL增加0.20 cmH2O×mL-1×s所需的MCh浓度显著降低。在一些大鼠中，MCh高反应性和RL变化在暴露后分别持续长达1个月和3个月。组织学评估及形态计量学评估显示上皮扁平化、坏死、平滑肌质量增加以及上皮再生迹象。BAL显示中性粒细胞数量增加。上皮出现最大异常的时间（第1 - 3天）与最大功能变化的时间一致。急性高氯暴露导致功能和病理异常，在大多数动物中经过一段可变时间后可恢复；然而，这些变化在一些动物中可能持续存在。初始阶段的功能异常可能与气道上皮损伤有关。
