Lung Defense Mechanisms from Environmental Ozone

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EXCEED THE SPACE PROVIDED. The incidence of asthma has increased dramatically in industrialized countries over the last 20 years. Currently approximately 17 million people have been diagnosed with asthma in the U.S. Epidemiological and human clinical studies have shown that inhalation of the photochemical air pollutant ozone exacerbates asthma. This exacerbation can be characterized by two responses. First, asthmatics have been shown to have greater pulmonary function decrements, symptoms and airway inflammation when acutely exposed to ozone. Second, the acute inhalation of ozone has been shown to increase the responsiveness to an inhaled allergen in patients with atopic asthma. The underlying mechanisms involved in these ozone-asthma interactions remain undefined. We hypothesize that these ozone-asthma interactions are mediated by either reflex responses involving the central nervous system or the release of neuropeptides from afferent nerve endings located in the airway. To test this hypothesis we have devised the following four specific aims: Specific Aim 1,In Brown-Norway rats sensitized and challenged with ovalbumin, we will determine which group of lung vagal afferents (myleinated vs. nonmyleinated) contribute to the airway responses associated with ozone-asthma interactions by blocking vagal C-fiber conduction with perineural capsaicln treatment and then combining the C-fiber block with cold block of mylenated vagal fibers. Specific Aim 2, using single nerve fiber recording techniques we will examine the discharge pattern of vagal afferent fibers following an acute inhalation of ozone in Brown-Norway rats that have been sensitized and challenged with ovalbumin and during a subsequent allergen aerosol challenge. Specific Aim 3, we will examine the influence that the neuropeptides, substance P (SP) and calcitonin gene related peptide (CGRP) have on the migration of and cytokine production from inflammatory/immunecells and epithelial cells. Specific Aim 4, we will examine the role of SP, CGRP and vasoactive intestinal peptide (VIP) in airway epithelial and lymph node proliferative responses following an acute inhalation of ozone in normal and ovalbumin sensitized and challenged rats. The information obtained from these studies will help define the ozone-asthma mechanisms that lung sensory nerves mediate during acute exposure to ozone in allergen sensitized animals and may provide insight into basic mechanisms that influence diseases that involve airway epithelial injury. PERFORMANCE SITE ========================================Section End===========================================