E. R. McFadden

Exercise-induced asthma is a condition in which vigorous physical activity triggers acute airway narrowing in people with heightened airway reactivity. A more accurate description would be exercise-induced bronchospasm. Long usage, however, has left the former term firmly fixed in the lexicon. To emphasize the underlying pathogenesis, the term “thermally induced asthma” has been proposed1.Exercise-induced asthma is not an isolated disorder or a specific disease. Exercise is but one of many stimuli that result in a limitation of airflow. It is not uncommon for physical exertion to be the first precipitant of asthma. With time, however, others may emerge. . . .

To compare the degree of bronchial obstruction and the clinical manifestations of asthma, we correlated lung mechanics with subjective complaints and physical findings in 22 patients during acute attacks of bronchospasm, and serially during therapy. Only the sign of retraction of the sternocleidomastoid muscle consistently identified those who had severe impairment of pulmonary function; dyspnea and wheezing did not. Regardless of the initial presentation of the patients, when they became asymptomatic, the overall mechanical function of their lungs ranged between 40 and 50 per cent of predicted normal values. When they were without signs of asthma, lung function was only 60 to 70 per cent of predicted values. These abnormalities appear to result from persistent airflow obstruction residing in peripheral airways that is not sufficient to induce symptoms at rest but compromises pulmonary function and may serve as a base for future recurrent episodes of asthma.

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.

To characterize the intrathoracic thermal events that occur during breathing in humans, we developed a flexible probe (OD 1.4 mm) containing multiple thermistors evenly spaced over 30.2 cm, that could be inserted into the tracheobronchial tree with a fiberoptic bronchoscope. With this device we simultaneously recorded the airstream temperature at six points from the trachea to beyond the subsegmental bronchi in six normal subjects while they breathed ambient and frigid air at multiple levels of ventilation (VE). During quiet breathing of room air the average temperature ranged from 32.0 +/- 0.05 degrees C in the upper trachea to 35.5 +/- 0.3 degrees C in the subsegmental bronchi. As ventilation was increased, the temperature along the airways progressively decreased, and at a VE of 100+ 1/min the temperature at the above two sites fell to 29.2 +/- 0.5 and 33.9 +/- 0.8 degrees C, respectively. Interval points were intermediate between these extremes. With cold air, the changes were considerably more profound. During quiet breathing, local temperatures approximated those recorded in the maximum VE room-air trial, and at maximum VE, the temperatures in the proximal and distal airways were 20.5 +/- 0.6 and 31.6 +/- 1.2 degrees C, respectively. During expiration, the temperature along the airways progressively decreased as the air flowed from the periphery of the lung to the mouth: the more the cooling during inspiration, the lower the temperature during expiration. These data demonstrate that in the course of conditioning inspired air the intrathoracic and intrapulmonic airways undergo profound thermal changes that extend well into the periphery of the lung.

Maximum expiratory flow rate at 30 percent of vital capacity above residual volume served as an index of airway obstruction in comparing the effects of leukotriene C and histamine administered by aerosol to five normal persons. Leukotriene C was 600 to 9500 times more potent than histamine on a molar basis in producing an equivalent decrement in the residual volume. The leukotriene C response was slow in onset and prolonged, reminiscent of the effects of aerosol allergen challenge in asthmatic allergic subjects.