MECHANISMS OF HUMAN AIRWAY REACTIONS TO DRY AIR

哮喘患者在过度换气时出现支气管痉挛 空气，许多人在暴露于空气中时会出现鼻炎症状 以适应干燥寒冷的环境。在这两种情况下，高流量的干燥空气 呼吸道粘膜似乎是触发刺激。发病机制 这些反应中有哪些是未知的，需要澄清，因为它们 对慢性哮喘和哮喘的发病率有显著影响 鼻炎。人的鼻黏膜非常容易进行实验。 可为上、下丘脑的病理生理提供有价值的信息。 以及降低对干燥空气的呼吸道反应。我们已经开发了一些方法来 高流量诱发敏感个体实验室鼻炎 鼻腔吸入冷或热的干燥空气。我们从这里观察到的 模型得出了我们的假设，即鼻黏膜对干燥空气敏感 在极端情况下，个人可能无法充分湿化吸入的空气。 条件。由于这个问题，呼吸道衬里液体变得 会发生高渗透压和上皮干燥和脱落。 高张激活肥大细胞释放炎症介质和 产生神经反射，导致神经源性炎症。我们现在 建议对这一假设的几个方面进行检验。两个截然不同的群体 在人类志愿者中，那些对干燥空气有鼻敏感和没有鼻敏感的人， 将在这些研究中进行比较。通过插入带有湿度的探头 和温度传感器进入鼻咽部，我们将直接测量 鼻黏膜调节吸入空气的能力。组织切片检查 粘膜将提供可能的形态变化的信息，这些变化可能 干扰水路运输。电势的测量 在活体鼻黏膜与干燥空气反应者和 无反应的人将检查离子变化的可能性 运输与干燥的空气反应有关。区别于 高渗透压和降温作为神经成分的触发因素 我们将检查对干燥空气的反应是否会产生反射 高渗液局部鼻腔刺激后或术后 单侧粘膜降温。我们将尝试对神经肽进行量化 在干空气刺激后的鼻腔冲洗中，并将进一步检查其 通过耗尽神经肽的粘膜在反应中的作用 重复使用辣椒素。这个项目将使我们能够 阐明人类呼吸道对干燥空气和CAN的反应机制， 因此，为慢性阻塞性肺疾病的治疗开辟了新的治疗途径。 鼻炎和哮喘。

Patients with asthma experience bronchospasm upon hyperventilation of dry air, and many individuals experience symptoms of rhinitis when exposed to dry and cold environment. In both cases, high flow of dry air over the airway mucosa seems to be the triggering stimulus. The pathogenesis of these reactions is unknown and needs to be elucidated because they contribute significantly to the morbidity from chronic asthma and rhinitis. The human nasal mucosa is very accessible to experimentation and can provide valuable information on the pathophysiology of both upper and lower airway reactions to dry air. We have developed methods to induce rhinitis in the laboratory in sensitive individuals by high flow nasal inhalation of cold or hot dry air. Our observations from this model led to our hypothesis that the nasal mucosa of dry air sensitive individuals may not be able to adequately humidify inhaled air at extreme conditions. Because of this problem, the airway lining fluid becomes hyperosmolal and epithelial desiccation and detachment occurs. Hypertonicity activates mast cells to release inflammatory mediators and generates neural reflexes resulting in neurogenic inflammation. We now propose to test several aspects of this hypothesis. Two distinct groups of human volunteers, those with and without nasal sensitivity to dry air, will be compared in these studies. By inserting a probe with humidity and temperature sensors into the nasopharynx we will directly measure the capacity of the nasal mucosa to condition inhaled air. Biopsies of the mucosa will provide information on possible morphologic changes that may interfere with water transportation. Measurements of the potential difference across the nasal mucosa in vivo from dry air responders and nonresponders will examine the possibility that alterations in ion transport are related to the dry air reaction. To differentiate between hyperosmolality and cooling as the trigger for the neural component of the reaction to dry air we will examine whether reflexes are generated after localized nasal stimulation with hyperosmolal solutions or after unilateral mucosal cooling. We will attempt to quantify neuropeptides in nasal lavages after dry air provocation and will further examine their role in the reaction by depleting the mucosa of neuropeptides with repetitive capsaicin applications. This project will allow us to elucidate the mechanisms of the human airway response to dry air and can, therefore, lead to new therapeutic approaches in the treatment of chronic rhinitis and asthma.