ANIMAL MODELS OF COLD AIR-INDUCED AIRWAY DISEASE

描述（由申请人提供）：吸入的空气通过上气道进行调节（加温和加湿），以防止肺实质冷却和干燥。 虽然这个过程通常是成功的，但在严酷的条件下，如在寒冷的环境中进行剧烈运动，未经调节的空气会渗透到外周气道。 在这种刺激后，哮喘患者的急性气道阻塞是常见的。 也可能发生轻度气道阻塞和炎症的晚期反应。 最重要的是，在寒冷环境中反复锻炼的人患慢性气道疾病的几率很高，这表明反复的冷却和干燥会导致持续的气道损伤。 在犬实验室外周气道冷却和干燥模型中的研究支持冷空气反复过度通气可导致气道损伤和炎症的假设。 然而，该模型对人体运动的适用性受到质疑，因为该模型使用单向气流而不是振荡气流来产生初始刺激。 单向气流防止在呼气期间回收水，并且因此可能在呼吸过度期间夸大气道干燥。 赛马和比赛雪橇犬通常在寒冷的环境中进行剧烈运动。 初步研究表明，这些动物也经历外周气道冷却和干燥。 如果这些动物经历了与人类相同的气道损伤和功能障碍谱，那么赛马和比赛雪橇犬可以作为研究寒冷天气引起的人类气道疾病的有价值的动物模型。 在这个项目中，急性，延迟，和长期的外周气道反应剧烈的寒冷天气运动在这些模型将被检查，以确定其在类似的人类条件的研究中的有用性。 具体而言，狗和马将进行剧烈的跑步机运动，同时呼吸寒冷的空气，并将测量肺阻力、反应性和广泛的气道炎症标志物，以表征对单一冷空气挑战的气道反应，其方式与来自人类的现有数据相同。 研究人员将使用这些相同的测量来确定在寒冷环境中进行重复运动的狗的肺力学和气道炎症的变化。

DESCRIPTION (provided by applicant): Inspired air is conditioned (warmed and humidified) by the upper airways to prevent cooling and desiccation of the lung parenchyma. Although this process is usually successful, under severe conditions such as strenuous exercise in frigid environments, unconditioned air penetrates into the peripheral airways. Acute airway obstruction in asthmatic humans is common after this stimulus. A late phase response of mild airway obstruction and inflammation may also occur. Most importantly, the high incidence of chronic airway disease in people that repeatedly exercise in frigid environments suggests that repeated cooling and drying can lead to persistent airway injury. Studies in a canine laboratory model of peripheral airway cooling and drying support the hypothesis that repeated hyperventilation with cold air can lead to airway injury and inflammation. However, the applicability of this model to human exercise has been questioned because the model uses unidirectional, rather than oscillatory, airflow to produce the initial stimulus. Unidirectional airflow prevents the reclamation of water during exhalation, and thus, may exaggerate the airway drying during hyperpnea. Racehorses and racing sled dogs routinely perform strenuous exercise in cold environments. Pilot studies suggest that these animals also experience peripheral airway cooling and drying. If these animals experience the same spectrum of airway injury and dysfunction as is reported in humans, then racehorses and racing sled dogs could serve as valuable animal models for study of cold weather-induced airway disease in humans. In this project, the acute, delayed, and long-term peripheral airway responses to strenuous cold weather exercise in these models will be examined to determine their usefulness in the study of the analogous human condition. Specifically, dogs and horses will perform strenuous treadmill exercise while breathing frigid air and pulmonary resistance, reactivity, and a wide range of markers of airway inflammation will be measured to characterize the airway responses to a single cold air challenge in the same manner as existing data derived from humans. The investigators will use these same measurements to determine the changes in pulmonary mechanics and airway inflammation in dogs that perform repeated exercise in frigid environments.