ANIMAL MODELS OF COLD AIR-INDUCED AIRWAY DISEASE

描述（由申请人提供）：吸气空气由上呼吸道调节（加热和加湿），以防止肺实质的冷却和干燥。虽然这个过程通常是成功的，但在恶劣的条件下，如在寒冷的环境中剧烈运动，无条件的空气会渗透到周围的气道。在这种刺激后，哮喘患者的急性气道阻塞是常见的。轻度气道阻塞和炎症的晚期反应也可能发生。最重要的是，在寒冷环境中反复运动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。在犬周围气道冷却和干燥的实验室模型中进行的研究支持了反复使用冷空气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。单向气流阻止了呼气过程中水分的回收，因此，可能会加剧呼吸急促时气道的干燥。赛马和雪橇犬经常在寒冷的环境中进行剧烈运动。初步研究表明，这些动物也会经历周围气道冷却和干燥。如果这些动物经历了与人类相同的气道损伤和功能障碍，那么赛马和比赛雪橇狗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。在本项目中，将检查这些模型中对剧烈寒冷天气运动的急性、延迟和长期外周气道反应，以确定它们在类似人类状况研究中的实用性。具体来说，狗和马将在呼吸寒冷空气的同时进行剧烈的跑步机运动，肺部阻力、反应性和气道炎症的广泛标记将被测量，以表征气道对单一冷空气挑战的反应，其方式与现有的人类数据相同。研究人员将使用这些相同的测量来确定在寒冷环境中反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.