E. C. Deal

We have hypothesized that it is the total heat flux in the tracheobronchial tree during exercise that determines the degree of postexertional obstruction in asthma, and have developed quanititative expressions that relate these two events. We tested this hypothesis by comparing the observed responses to exercise, while our subjects inhaled dry air at various temperatures ranging from subzero to 80 degrees C in a random fashion, to those that we predicted would occur based upon calculations of respiratory heat exchange. We further determined if heat could be transferred from the inspired air to the mucosa so as to offset evaporative losses from the airways. The observed responses fell as air temperature was increased from -11 to +37 degrees C and exactly matched theoretical predictions. Above 37 degrees C, the observed response exceeded predictions, indicating that it was not possible to provide sufficient heat per se in the air to offset the vaporization of water. However, when small amounts of water vapor were added to the inspirate at high temperatures, bronchospasm was virtually abolished and the response again closely matched theoretical expectations. We conclude that the magnitude of exercise-induced asthma is directly proportional to the thermal load placed on the airways and that this reaction is quantifiable in terms of respiratory heat exchange.

A C T We examined the degree of airway obstruction that developed in eight asthmatics who exercised while breathing air under four conditions: (a) ambient room temperature and water content; (b) body temperature and ambient water content; (c) ambient room temperature fully saturated; and (d) body temper- ature fully saturated. These test conditions were performed in random order. Multiple aspects of pulmonary mechanics were measured before and 5 min after exercise. When air at ambient conditions was inhaled, the expected airway obstruction developed after exercise, and all variables changed significantly from their pre-challenge values. Heating the air to body temperature did not influence this response. Increasing the humidity at ambient temperatures significantly blunted the response, and by inhaling body temperature, fully saturated air completely prevented it from occurring. Thus, the water content of inspired air is an important variable in the development of exercise- induced asthma.

It was previously demonstrated that the magnitude of post exertional asthma is proportional to the heat exchange that occurs within the airways. Since the level of ventilation is an important determinant of the quantity of heat transferred from the mucosa, it was reasoned that if we simulated the hyperpnea of exercise by hyperventilation, heat exchange would be produced similar to that seen with exercise, and thus equivalent bronchial obstruction. To test this hypothesis, 8 asthmatics performed eucapnic hyperventilation to mean levels of 63 and 44 L/min while they breathed dry air at subfreezing (-12 C) and room temperature (23 C) and fully saturated air at room and body temperature through a heat exchanger in a random order. Hyperventilation at body conditions (0 heat flux) did not result in any change in pulmonary mechanics. However, as the water content and temperature of the inspirate were decreased, thus increasing the thermal burden on the airways at maximal ventilation (V sub E), the bronchospastic response progressively increased. Decreasing the thermal burden by decreasing V sub E proportionally reduced the response. From this we conclude that the major stimulus for exercise-induced asthma is heat loss from the mucosa with subsequent cooling, which is precipitated by the hyperpnea of exercise but not exercise per se.

To determine whether mediators of immediate hypersensitivity played a role in the pathogenesis of exercise-induced asthma, we measured the concentration of histamine and neutrophil-chemotactic activity present in systemic arterial blood during thermal challenges in five asymptomatic asthmatics. Because exercise-induced asthma has been shown to be a result of respiratory heat loss and because respiratory heat loss during isocapnic hyperventilation has been shown to give identical responses, we chose the latter provocational method in order to minimize increases in cardiac output that might interfere with the interpretation of mediator concentrations in arterial blood. Multiple aspects of pulmonary mechanics were also recorded before and after provocation. The results of these studies were then compared with the effects observed when the same subjects inhaled aerosols of specific antigens on the same day. Each challenge produced identical alterations in lung function, and neither was associated with consistent changes in arterial histamine. However, antigen provocation evoked a sustained and prolonged release of neutrophil chemotactic activity in each subject, whereas isocapnic hyperventilation with cold air was without effect. These data strongly suggest that mast-cell derived mediators are not involved in the development or maintenance of the bronchial obstruction that follows exercise in asthmatics.