Exercise-induced asthma: Observations on the initiating stimulus.
Explore the source record for details and available documents.
Acidosis↗
Biomedical subjects
R H Ingram
Publications and source records attributed to R H Ingram.
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.
Explore the source record for details and available documents.
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↗
Rib cage deformation during static inspiratory efforts.
Patterns of rib cage (RC) deformation were studied in six normal subjects during moderate static inspiratory efforts such that esophageal pressure (Pes) as an index of transthoracic pressure fell to between -30 and -60 cmH2O during each maneuver. At lung volumes below 50% inspiratory capacity (IC), static inspiratory efforts deformed RC to a more elliptical shape; RC lateral diameter became smaller and RC lateral diameter became larger. However, at high lung volumes (greater than 50% IC) the opposite change in RC dimensions occurred despite similar changes in Pes, i.e., the RC became more circular. These differences in RC deformation did not appear to be a possive consequence of increased lung volume because the RC could be voluntarily deformed to a more circular shape at low lung volume when a) subjects performed static inspiratory efforts mainly with their intercostal and accessory muscles rather than their diaphragm as judged by a smaller change in transdiaphragmatic pressure for the same Pes; or b) subjects statically contracted their diaphragm with it held in a relatively flattened configuration as assessed by a large abdominal AP dimension. We suggest that deformation of the RC during static inspiratory efforts is not as predictable as has previously been suggested but depends on the pattern of contraction and configuration of the respiratory muscles.
Adult↗
Vagal effects on histamine, carbachol, and prostaglandin F2 alpha responsiveness in the dog.
To investigate whether an individual dog's responsiveness to histamine correlates with its responsiveness to other bronchoconstrictor agents and to investigate whether varying vagal effects account for the previously described range of histamine responsiveness, we compared dose-effect relationships of histamine to those of two pharmacological dissimilar agents, carbachol and prostaglandin F2 alpha before and after vagal blockade. There was a highly significant correlation between histamine and both carbachol (P less than 0.001) and prostaglandin F2 alpha (P less than 0.001) responsiveness. The range of responsiveness to prostaglandin F2 alpha was greater than that for histamine or carbachol. When histamine and carbachol were given simultaneously, a purely additive effect was found. Vagal blockade had no significant effect on histamine or carbachol responsiveness, but significantly diminished the responsiveness to prostaglandin F2 alpha; however, it neither narrowed the range nor changed the rank order of responsiveness. We conclude that the range of responsiveness is not specific for any one agent and that vagal mechanisms do not play a role in producing this range.
Airway Resistance↗
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↗
Effects of volume history on airway changes induced by histamine or vagal stimulation.
Explore the source record for details and available documents.
Animals↗
Changes in canine left ventricular size and configuration with positive end-expiratory pressure.
Explore the source record for details and available documents.
Animals↗
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↗
Apical fibrobullous disease with rheumatoid arthritis.
We describe a patient who developed noninfectious apical fibrobullous disease 12 years after the diagnosis of seropositive, nodular, deforming rheumatoid arthritis. Fibrobullous disease of the pulmonary apices is a rare entity that is usually found in association with ankylosing spondylitis. Its appearance with rheumatoid arthritis has not been reported. Speculative factors which may predispose to apical fibrobullous disease, such as a stiff chest wall, impaired esophageal motiligy, and HL-A antigen B27, were not present in our patient.
Adult↗
Bilateral diaphragmatic paralysis with hypercapnic respiratory failure. A physiologic assessment.
Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H2O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.
Aged↗
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↗
Distribution of pulmonary responsiveness to aerosol histamine in dogs.
Dose-response curves to aerosol histamine in 102 anesthetized, intubated, spontaneously breathing dogs revealed a spectrum of airway responsiveness with a greater than 40-fold difference between the most and the least sensitive animals. The frequency distribution of responses fits a log normal distribution. No correlation was found between sex, age, or control values of dynamic compliance (Cdyn) and lung resistance (RL) and the dose of histamine required to cause a response. Repetitive studies in 17 dogs observed for up to 20 mo showed that the dose at which an individual dog would respond was reproducible within a narrow range and that the differences between dogs were highly significant (P greater than 0.001). The long-term reproducibility of the response to aerosol histamine in individual dogs suggests that short-term reversible airway insults are not responsible for the range in responses noted between animals.
Aerosols↗
Vagal and aerosol histamine interactions on airway responses in dogs.
Histamine aerosol was administered to 10 anesthetized paralyzed artificially ventilated dogs whose vagi were first intact, then cut, and then peripherally stimulated. Pulmonary resistance (RL) was measured and dose-response curves determined in the three conditions. The dogs were divided into two groups based on the initial response to histamine with the vagi intact. The low-dose (LD) group had a greater than or equal to 50% increase in RL when exposed to a histamine concentration of 1.0 mg/ml. The high-dose (HD) group had a greater than or equal to 50% increase in RL when exposed to an aerosol containing 3.0 mg/ml histamine or more. In both groups there was a dose-related increase in RL with histamine with the vagi intact, cut, or stimulated. In three of the LD dogs there was a greater than additive interaction between vagal stimulation and inhaled histamine, whereas in the HD dogs the interaction was at most additive. With the vagi cut, both groups had a significantly lesser histamine response. The results show that differences in histamine responsiveness between dogs is in part related to varying degrees of nonreflex histamine-vagal interaction.
Aerosols↗
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↗