Exercise-induced asthma: Observations on the initiating stimulus.
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Acidosis↗
Biomedical subjects
E R McFadden
Publications and source records attributed to E R McFadden.
Role of respiratory heat exchange in production of exercise-induced 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.
Adult↗
Hyperpnea and heat flux: initial reaction sequence in exercise-induced asthma.
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Adult↗
Esophageal temperature during exercise in asthmatic and nonasthmatic subjects.
We measured the temperature in the rectum and two esophageal sites (retrocardiac and retrotracheal) during exercise in eight asthmatic and six normal subjects while they breathed air at subfreezing, ambient, and body conditions. Various aspects of pulmonary mechanics were recorded before and after exercise. The asthmatic subjects developed the greatest airway obstruction following exercise with cold air and no response at body conditions. There were no changes in pulmonary mechanics in the postexercise period in the normal individuals with any of the inspired air conditions. Despite these divergent mechanical responses retrotracheal temperatures fell by the same magnitude below core values in both groups of subjects, indicating that identical degrees of airway cooling occurred. We conclude that rather than having a defect in the ability to condition inspired air, asthmatic subjects are more responsive to the effects of incompletely conditioned air.
Adult↗
Pattern and mechanism of airway response to hypocapnia in normal subjects.
We examined the bronchoconstriction produced by airway hypocapnia in normal subjects. Maximal expiratory flow at 25% vital capacity on partial expiratory flow-volume (PEFV) curves fell during hypocapnia both on air and on an 80% helium- 20% oxygen mixture. Density dependence also fell, suggesting predominantly small airway constriction. The changes seen on PEFV curves were not found on maximal expiratory flow-volume curves, indicating the inhalation to total lung capacity substantially reversed the constriction. Pretreatment with a beta-sympathomimetic agent blocked the response, whereas atropine pretreatment did not, suggesting that hypocapnia affects airway smooth muscle directly, not via cholinergic efferents.
Adult↗
A critical assessment of the mechanism by which hyperoxia attenuates exercise-induced asthma.
Recent data demonstrate that the magnitude of the heat loss that occurs from the respiratory tract during exercise correlates with the degree of post-exertional obstruction that develops in asthmatics. Respiratory heat loss relates directly to the minute ventilation and heat capacity of the inspired gas and inversely to its water content and temperature. Because it has been shown that inhaling 100% oxygen during exercise blunts the obstructive response, we wondered if this effect could be accounted for by differing values of heat exchange with air and oxygen breathing. To examine this question, we studied 10 asthmatics by measuring multiple aspects of pulmonary mechanics before and after four bouts of exhausting leg work during which the subjects inhaled either air or oxygen conditioned to provide widely differing thermal burdens on their airways. Under all inspired gas conditions, oxygen breathing produced significantly less obstruction than air. Minute ventilation was also significantly less with oxygen as was the total heat lost. As the latter fell, so did the magnitude of the postexercise obstruction. When the differences in ventilation and respiratory heat loss between air and oxygen were eliminated by eucapnic hyperventilation, the differences in the obstructive responses also disappeared. Thus, the effects of hyperoxia on exercise-induced asthma can be accounteed for solely by alterations in heat exchange.
Adult↗
Effects of prostaglandin F2alpha on lung mechanics in nonasthmatic and asthmatic subjects.
Prostaglandins have been implicated as secondary pharmacologic mediators in allergic bronchial asthma. We have studied the effects of the intravenous infusion of prostaglandin F2alpha (PGF2alpha) on pulmonary mechanics in nonasthmatic and asthmatic volunteers. Before and during the infusion, measurements were made of total lung capacity and its subdivisions, static deflational transpulmonary pressure-volume relationships (PV), and maximal expiratory flow-volume curves with air and after a washing of an 80% helium-20% oxygen mixture. In both groups, PGF2alpha caused significant decreases in vital capacity and maximal flow and increases in residual volume. There were not significant differences between groups in either the absolute magnitude or the percent change in the variables, a result which may have been due to the similarity of the pulmonary mechanics in both groups prior to infusion. Changes in density dependence were bidirectional in both groups, indicating that relative contributions of large and small airways to flow limitation changed differently among individuals. The single between-group difference in responses noted was a leftward shift of the PV curve in the asthmatics, suggesting recoil of the lung which occurs in asthma.
Adult↗
Influence of abdominal gas on the Boyle's law determination of thoracic gas volume.
In a body plethysmograph we have demonstrated differences in total lung capacity (TLC) derived from panting maneuvers performed at different levels in the vital capacity. In almost all cases, the discrepancies were due to the magnitude of the abdominal gas volume (AGV) and the relative magnitude of abdominal and thoracic pressure swings during the panting mandeuver. When panting was performed at functional residual capacity (FRC), the effect of AGV compression on the determination of thoracid gas volume (TGV) was small. Of 11 individuals studied 2 were known to have mild asthma. Compression and decompression of AGV appeared to be an insufficient explanation for discrepancies in derived TLC's in these two, suggesting that other as yet unidentified factors may influence the plethysmographic determination of TGV.
Gases↗
Effects of atropine on potentiation of exercise-induced bronchospasm by cold air.
The role of vagal efferent activity in the cold air potentiation of exercise-induced asthma was assessed by exercising nine subjects who breathed air at ambient and subfreezing temperatures before and after cholinergic blockade. Lung volumes and maximal expiratory flow volume curves with air and with 80% helium-20% oxygen were obtained before and 5--10 min after each challenge. Isovolume comparisons of maximal expiratory flow rates with the two gases were used to assess relative contributions of large and small airways to flow limitation. Exercise under ambient conditions resulted in the expected airway obstruction and cold air exaggerated the response. Atropine pretreatment had no effect on the cold air potentiation. After atropine with ambient air exercise, there was an increase in the relative contribution of large airways to flow limitation, whereas exercise with cold air resulted in an increase in the contribution of small airways. We concluded that the potentiating effects of cold air are local and suggest that the immediate stimulus is related to cooling of intrathoracic airways.
Adult↗
Distribution of bronchodilatation in normal subjects: beta agonist versus atropine.
Bronchodilatation was produced in normal subjects by the inhalation of a parasympatholytic agent (atropine) and the response was compared to that occurring after the inhalation of a beta-adrenergic agent (isoetharine). Doses were chosen that resulted in equivalent increases in specific airway conductance (78 +/- 9% for atropine; 88 +/- 21% for isoetharine). Anatomic dead space and volume at the onset of the terminal nitrogen rise (closing volume) were measured before and after each agent. Although there was no difference in the degree of overall bronchodilatation after the two drugs, anatomical dead space increased significantly more after atropine than isoetharine (+17% vs. +6%, P less than 0.01), and closing volume increased significantly after isoetharine (P less than 0.005) but did not change with atropine. We interpret these differences to indicate a greater effect of cholinergic antagonists on the more central airways and a greater effect of beta-adrenergic stimulants on peripheral airways.
Adult↗
Problems in the plethysmographic assessment of changes in total lung capacity in asthma.
We studied the effect of abdominal gas compression on plethysmographically determined total lung capacity (TLC) in asthmatic patients before, during, and after treatment of induced bronchospasm. TLC was derived from panting maneuvers near residual volume, at functional residual capacity, and near TLC. Significant differences among these "derived TLC" values increased significantly during bronchospasm. Whether or not TLC appeared to increase, and by how much, depended on the level of the vital capacity from which it was derived. Individual increases in TLC during bronchospasm could not be explained by increases in abdominal gas volume or in the extent to which it was compressed and decompressed during panting. We postulate that during the Boyle's Law panting maneuver, pleural, and therefore alveolar, pressure swings may be nonhomogeneous and greater over lung regions subtended by closed airways than over regions in communication with the mouth. This would result in an underestimation of alveolar pressure swings as measured at the mouth and an overestimation of thoracic gas volume, and would account in large part for the observed increase in discrepancies between the "derived TLC" values in asthma as well as the dependence of apparent TLC changes on the level of the VC at which the panting maneuver is performed.
Asthma↗
Influence of heat and humidity on the airway obstruction induced by exercise in asthma.
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 temperature 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 changes 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.
Adult↗
Enhancement of exercise-induced asthma by cold air.
To study the possibility that the inhalation of cold air accentuates the bronchoconstrictor response to exercise in asthma, eight subjects exercised while breathing air at ambient or subfreezing temperatures. On a separate day, cold air was breathed at rest so as to isolate the effects of this stimulus. Pulmonary mechanics were measured before and after each experiment. In all subjects acute bronchoconstriction followed the control exercise challenge. With cold-air breathing, however, the magnitude of the response was markedly enhanced. Residual volume increased 158 per cent more than it did previously, and specific conductance and one-second forced expiratory volumes changed an additional 85 and 100 per cent, respectively. The effects of cold air at rest were very small. The results demonstrate a positive interaction of two common naturally occurring stimuli in the induction of asthmatic attacks, and constitute objective verification of a frequent clinical complaint.
Adult↗
Localization and mechanisms of airway responses.
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Airway Obstruction↗
Asthma: pathophysiology and clinical correlates.
Sufficient data has now accumulated that demonstrates that a careful analysis of the presenting signs and symptoms of a patient with acute asthma will permit clinically useful conclusions to be drawn regarding the magnitude and severity of the underlying airway obstruction and the expected response to therapy. If a patient with severe obstruction deviates from this expected course, objective measurements of mechanical function and gas exchange should be obtained. In our current state of knowledge, these measurements should then be used as the prime indices of therapeutic effectiveness and less reliance should be placed on traditional clinical approaches.
Acute Disease↗