Davis Michael S, Schofield Brian, Freed Arthur N
Department of Environmental Health Sciences, School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
Med Sci Sports Exerc. 2003 Apr;35(4):608-16. doi: 10.1249/01.MSS.0000058660.88987.A0.
INTRODUCTION/PURPOSE: Elite winter athletes have an increased incidence of asthma, the cause of which is unknown. Strenuous exercise, particularly while breathing cold air, results in airway cooling and desiccation. We used a canine model of hyperpnea with cold, dry air to test the hypothesis that repeated cooling and desiccation of peripheral airways can cause asthma-like pathology.
Canine sublobar airways were challenged with room temperature, dry air insufflated though a bronchoscope to simulate the mucosal cooling and desiccation that occurs in human peripheral airways during strenuous cold weather exercise. Airways were challenged once daily on four consecutive days, and control and challenged airways were harvested 24 h after the last challenge for histological analyses.
Repeated challenge caused airway obstruction and remodeling that persisted for at least 24 h. The percentage of mucosal squamous epithelium increased with a corresponding decrease in ciliated epithelium. Challenged airways had thicker lamina propria that contained greater concentrations of eosinophils, neutrophils, and mast cells when compared with control airways. The severity of airway obstruction was correlated with mucosal condition, airway thickness, and eosinophil infiltration. With the exception of mast cell infiltration, all changes were reversed within 1 wk of cessation of challenges.
We conclude that repeated cooling and desiccation of peripheral airways can cause airway remodeling similar to that seen in asthma. These findings, in concert with other reports using this model, support the hypothesis that asthma-like symptoms found in winter athletes may be the result of repeated hyperpnea with cold air.
引言/目的：优秀的冬季运动员哮喘发病率增加，但其病因尚不清楚。剧烈运动，尤其是在呼吸冷空气时，会导致气道冷却和干燥。我们使用冷空气干燥条件下的犬类深呼吸模型，来检验外周气道反复冷却和干燥会导致哮喘样病理变化这一假设。
通过支气管镜向犬类肺叶亚段气道吹入室温干燥空气，以模拟人类在寒冷天气剧烈运动时外周气道发生的黏膜冷却和干燥。连续四天每天对气道进行一次刺激，在最后一次刺激后24小时采集对照气道和受刺激气道用于组织学分析。
反复刺激导致气道阻塞和重塑，这种情况至少持续24小时。黏膜鳞状上皮的百分比增加，纤毛上皮相应减少。与对照气道相比，受刺激气道的固有层更厚，其中嗜酸性粒细胞、中性粒细胞和肥大细胞的浓度更高。气道阻塞的严重程度与黏膜状况、气道厚度和嗜酸性粒细胞浸润相关。除肥大细胞浸润外，所有变化在停止刺激后1周内均会逆转。
我们得出结论，外周气道反复冷却和干燥可导致类似于哮喘的气道重塑。这些发现与使用该模型的其他报告一致，支持了冬季运动员出现的哮喘样症状可能是反复冷空气深呼吸所致这一假设。
