ANIMAL MODELS OF COLD AIR-INDUCED AIRWAY DISEASE

冷空气诱发气道疾病的动物模型

• 批准号: 6661968
• 负责人: MICHAEL S DAVIS
• 金额: $ 30.1万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-23 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661968
• 关键词: airborne allergen; asthma; cold temperature; cytokine; disease /disorder model; dogs; eicosanoid metabolism; exercise; gene expression; high frequency ventilation; horses; hyperpnea; inflammation; lung; lung lavage; messenger RNA; model design /development; pathologic process; polymerase chain reaction; pulmonary respiration; respiratory airflow disorder; respiratory airflow measurement; respiratory function

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.

描述（由申请人提供）：吸入的空气通过上呼吸道进行调节（加热和加湿），以防止肺实质冷却和干燥。 尽管这个过程通常是成功的，但在严酷的条件下，例如在寒冷环境中进行剧烈运动，未经调节的空气会渗入周围呼吸道。 在这种刺激后，哮喘患者常见急性气道阻塞。 也可能发生轻度气道阻塞和炎症的晚期反应。 最重要的是，反复在寒冷环境中锻炼的人慢性气道疾病的发病率很高，这表明反复的降温和干燥会导致持续性气道损伤。 对犬类周围气道冷却和干燥实验室模型的研究支持了这样的假设：反复用冷空气过度换气会导致气道损伤和炎症。 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。 单向气流会阻止呼气期间水的回收，因此可能会加剧呼吸过度期间的气道干燥。 赛马和赛雪橇犬经常在寒冷的环境中进行剧烈运动。 初步研究表明，这些动物也经历了外周气道冷却和干燥。 如果这些动物经历与人类相同的气道损伤和功能障碍，那么赛马和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。 在该项目中，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，以确定它们在研究类似人类状况中的有用性。 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，并且将测量肺阻力、反应性和各种气道炎症标志物，以与现有数据相同的方式表征对单一冷空气挑战的气道反应源自人类。 研究人员将使用这些相同的测量结果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。