Most studies of exercise induced asthma focus on changes in airway function after exercise. However, there are changes in airway function that occur during exercise that are poorly described and poorly understood. In preliminary studies, we have found that bronchoconstriction can develop during exercise using protocols with either variable work intensity or a sustained constant work load. We have found that bronchodilation can also occur during exercise in asthmatic subjects.
The specific aims are designed to describe changes in airway function more completely and to investigate certain mechanisms for the changes in airway function during and after exercise.
In specific aim 1, we will use a guinea pig model of hyperventilation-induced bronchoconstriction to explore the roles of increased lung inflation and active bronchodilation via cyclooxygenase products as modulators of airway function during hyperventilation (a model for exercise).
In specific aim 2, we will compare exercise with isocapnic hyperventilation for the ability to alter airway function during and after the challenge to test the hypothesis that changes in airway function during exercise are due to physiological adaptations related to the exercise per se.
In specific aim 3, we will test the hypothesis that airway cooling is necessary for bronchodilation that is usually seen during exercise. We will perform exercise studies with an initial cool dry air stimulus followed by warm humid air or hot dry air to cause airway rewarming while still exercising. If the cooling theory is correct, we should demonstrate bronchoconstriction while still exercising.
In specific aim 4, we will test the hypothesis that arachidonic acid metabolites contribute to bronchodilation during exercise. If a bronchodilating prostaglandin is present during exercise, ingestion of the cyclooxygenase inhibitor, flurbiprofen, before exercise should cause airway resistance to be somewhat higher during exercise.
In specific aim 5, we will give subjects inhaled cromolyn sodium prior to exercise in an effort to block mast cell function during exercise. If mast cells are activated during exercise, then pulmonary resistances should be lower on the active drug day compared with placebo day. Results from these studies will allow us to design further studies to more fully elucidate mechanisms of exercise-induced changes in airway function in asthmatics. In addition, results from these studies may suggest therapies to improve airway function, particularly as related to exercise, in asthmatics.
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