The long term objectives of this proposal are to explore the cellular, biochemical and physiologic influences that control and modulate airway response in humans in health and disease. To achieve these goals, 4 sets of interrelated investigations are proposed. In the first, we will determine how naturally occurring viral infections influence the interrelationships among pulmonary mechanics, the function and population of inflammatory cells within the lung and eicosanoid production in subjects with normal airways and those with preexisting inflammatory changes from cigarette smoke and asthma. In the second set of studies, the mediator profile and inflammatory cellular pattern in the lungs of smokers with normal or heightened airway reactivity will be followed over time with smoking cessation and continuance and correlated with the physiological and clinical abnormalities present. The third series of investigations, will examine how immunologic and non-immunologic stimuli influence the state of airway inflammation and mediator generation in asthmatics and how these factors alter airway reactivity. The fourth group of experiments are designed to explore whether the bronchovascular circulation plays role in airway responsiveness. In these studies we will examine if vascular hyperemia and edema contribute to the obstructive response to thermal stimuli in conditions other than asthma. To achieve this end, intraairway temperatures will be directly recorded during maneuvers designed to alter the rate of airway cooling and rewarming. In toto, the information from this proposal will permit a detailed characterization of the histopathology and mediator profiles that develop within the lungs of humans, as well as an exploration of new pathophysiologic and pathogenetic process that may be at work, during common inflammatory conditions that are believed to contribute to the morbidity of patients with airway disease.
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