The long-term objective of this proposal is to determine the mechanism by which exercise produces airway obstruction in asthmatics. The attraction of studying this aspect of asthma is that exercise is a potent, naturally occurring stimulus that is potentially operational in the everyday life of all people with this illness. Thus, if one could unravel the manner in which exercise produces airway obstruction, it may be possible to gain great insights into the pathophysiology of asthma in general and ultimately into mechanisms for its control. The proposed studies are designed to: (1) determine the role played by mediators of immediate hypersensitivity in exercise-induced asthma; (2) examine whether ultrasonic aerosols influence the thermal environment within the airways and cause mediator release; (3) enumerate the factors controlling heat exchange within the airways in normal and asthmatic subjects; and (4) explore the potential role of the bronchial circulation in the production of airway obstruction with thermal stimuli. To achieve the first goal, we plan to have a group of asthmatics perform repetitive exercise challenges while serial measures of pulmonary function are recorded. Venous blood will be drawn at the same time as the lung function testing and will be assayed for its content of histamine and neutrophil chemotactic factor of anaphylaxis. In the second set of studies, we first propose to characterize the effects of inhaling ultrasonic aerosols on lung function by having asthmatic and normal subjects inhale various quantities of distilled H20, isotonic saline and two concentrations of hypertonic saline. To determine any potential thermal dependency, the temperatures of the aerosols will be varied in a systemic fashion. When this phase is complete, the subjects will exhale a quantity of aerosol of each solution known to reduce lung function a fixed amount and venous blood will be obtained for mediator analysis. The third and fourth goals will be achieved through an integrated set of investigations in asthmatic and normal volunteers. In the initial investigations the temperature and humidity of the air inhaled during recovery from a thermal challenge will be systematically varied to alter the rate of airway rewarming. In the second series, the temperature of the airstream within the intrathoracic airways will be recorded with a specially designed thermal probe before, during and after thermal challenges in the presence and absence of drugs that influence the bronchial circulation.
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