The objective of this proposal is to determine the mechanism by which thermal stimuli (exercise and hyperventilation) produce airway obstruction in asthmatics. The attraction of studying this aspect of asthma is that exercise is a potent, naturally occurring stimulus that is potentially in the everyday life of all people with this illness. The proposed studies are designed: 1) determine how chronic, and acute on chronic, changes in intrathoracic blood volume alter the mechanical consequences that follow hyperventilation and as the inhalation of non-isotonic aerosols affect airway thermodynamics; 2) to evaluate the changes that occur in the osmolarity of the surface fluid in the intrathoracic airways during hyperpnea; 3) to explore the role of airway inflammation and; 4) to ascertain if asthmatics differ from normal in the manner in which they regulate the vascular response to cold. To achieve this goal a group of normal and asthmatic volunteers will perform stimulus response curves to isocapnic hyperventilation and hypotonic saline when their plasma volumes are normal, elevated and reduced. The last two states will be achieved by oral salt loading and restriction respectively. On another occasion they will undergo bronchoscopy with insertion of thermal probe and will repeat the above challenges, while airstream temperatures are recorded continuously from mouth to the peripheral airways during hyperpnea and recovery. In the second set of studies the osmolarity of the surface fluid of the trachea will be measured at rest and during hyperpnea by placing a specially designed ion conductivity sensor on the air surface via bronchoscopy. The third goal will be obtained by measuring autocoid, prosinoid, and eicosinoid mediators and cytokines in airway fluid before and after antigen and exercise challenges in asthmatics.
The final aim will be accomplished by measuring surface blood flow in the fingers with a thermal conductivity sensor during and after exposure to cold.
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