MECHANISMS OF HUMAN AIRWAY REACTIONS TO DRY AIR

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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.