The Relationship between Exercise-induced Asthma and Plasma Catecholamines
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In asthmatics, exercise (E1) is known to induce bronchoconstriction; a second period of exercise (E2) within 30 to 90 min induces a lesser degree of bronchoconstriction. The reason for the “refractory” bronchoconstrictor response to E2 is unclear. We studied 6 normal subjects (Group 1) and 12 stable asthmatics to examine the possible relationship between the refractory period and sympathoadrenal function. The asthmatics were further divided into 2 groups, based on the absence (Group 2, n =5) or presence (Group 3) of an exercise-induced bronchoconstrictor response. In each subject/patient, after control measurements of spirometry and venous blood sampling, a standard level of treadmill exercise was performed, and blood and spirometry were obtained at 1, 5, 15, and 25 min after the end of exercise. A second period of treadmill exercise, of the same level and duration, was then performed, and blood sampling and spirometry were repeated at the same time intervals after the end of exercise. There was no significant (p < 0.1) difference in baseline plasma epinephrine (Ep), or norepinephrine (Np) levels; however, plasma dopamine (Op) levels were significantly (p < 0.05) higher in Group 3. In Groups 1 and 2, FEV1 did not change significantly after the first (E1) or second (E2) exercise periods, but there were significant (p < 0.01) changes in Group 3 (maximal percent changes in FEV1, ΔFEV1%, E1 = -14.4%, E2 = -8.8%), and the ΔFEV1% after E2 was significantly (p < 0.01) less that after E1. There were significant increases in Ep, Np, and Dp after exercise; however, there were no significant between-group differences in Ep, Np, or Dp, in post-E1 or post-E2 values, nor were there any significant wlthin-group differences in catecholamine values between E1 and E2. We conclude that there is no significant association between circulating catecholamines and the refractory period after exercise in asthma.Keywords:
Exercise-induced asthma
Blood sampling
Treadmill
Exercise-induced asthma
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To determine whether refractoriness to histamine induced bronchoconstriction occurs, 20 asthmatic subjects aged 19-50 years were tested. Subjects underwent two histamine challenge tests (1 and 2) on the same day, the second one being given 45-60 minutes after the first, once the FEV1 after test 1 had returned spontaneously to within 90% of baseline. A further "control" histamine challenge test was carried out on a different day at the same time (+/- 2 hours) as test 1. Bronchial responsiveness was recorded as the cumulative dose (microgram) of histamine provoking a 20% fall in FEV1 (PD20), and the ratio PD20 test 2:PD20 test 1 was used to assess refractoriness. The median value of this ratio (2.20) was significantly greater than 1 (p = 0.003), indicating refractoriness at the time of test 2. By contrast the median ratio PD20 control:PD20 test 1 of 1.03 was not significantly different from 1. Refractoriness could not be accounted for by failure to regain the initial baseline FEV1, though such failure may have exaggerated the effect. An increase in PD20 with the second test was observed uniformly in subjects with moderate or high initial PD20 values but not in those with low values. This suggests that there may be a PD20 threshold of the order 25-100 micrograms for refractoriness to occur. Refractoriness could exert an important confounding effect in investigations in which repeated histamine tests are carried out at short intervals.
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We investigated immediate and late changes in airway responsiveness to histamine, after bronchoconstriction due to exercise combined with inhalation of cold air, in ten asthmatic subjects who came on six days. On the first visit, the provocation concentration producing 20% fall in FEV1 (PC20) histamine was obtained. After functional recovery, each subject walked on a treadmill whilst breathing dry, cold air. This resulted in an immediate fall greater than 15% (mean +/- SD = 31.9 +/- 11.0%) in forced expiratory volume in one second (FEV1). Following recovery, PC20 was measured again. FEV1 was then monitored for up to 6-8 h. PC20 was measured then and on the two following days at the same time of the day. Subjects were studied on three control days using the same design except that a resting period replaced the exercise with cold air. The mean changes in PC20 at each interval after exercise combined with cold air were not statistically significant. Physiologically significant changes were obtained in only two subjects, reaching a maximum 8 h after the manoeuvre. In these subjects, changes in PC20 were reproducible during a second series of visits. It is concluded that bronchial responsiveness to histamine is not generally influenced by the bronchoconstriction due to exercise combined with cold air.
Exercise-induced asthma
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Exercise-induced asthma
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Educational aims Discuss the role of inhaled β-agonists in the management of exercise-induced asthma and exercise-induced bronchoconstriction. Review the beneficial versus untoward effects of inhaled β-agonists on asthma, exercise-induced asthma and exercise-induced bronchoconstriction. Report on current and past usage of these drugs by Olympic athletes. Summary Inhaled β-agonists effectively block exercise-induced asthma/exercise-induced bronchoconstriction (EIA/EIB). They are the treatment of choice for this condition and are used by many elite and Olympic athletes. However, regular or frequent use of inhaled β-agonists leads to an increase in the underlying severity of EIA/EIB and a reduction in their bronchoprotective and bronchodilator effects, which means that they become less effective at preventing and treating EIA/EIB. Emphasis should be placed on preventative measures and anti-inflammatory treatments such as inhaled corticosteroids in order to minimise the need for inhaled β-agonists to prevent EIA/EIB.
Exercise-induced asthma
Bronchodilator Agents
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Rationale: Impulse Oscillometry (IOS) is a noninvasive method to measure respiratory impedance.The use of IOS as an indirect measure of airflow obstruction compared to spirometry in the evaluation of Exercise-Induced Bronchoconstriction (EIB) has not been fully explored in children.In this study we aim to describe the IOS values, resistance at 5 Hz (R5rs) in subjects with EIB and without EIB.We also aim to compare whether IOS variables correlate with spirometry variables following exercise challenge test in asthmatic subjects. Methods:We designed a cross sectional study involving subjects between 6-18 years old with a diagnosis of asthma who were referred to the pediatric pulmonary function lab for an exercise challenge test to rule out EIB. Spirometry and IOS were performed at baseline and at 5 minute intervals up to 20 minutes post exercise and again post bronchodilator.Results: 43 subjects were enrolled.Of the 43 subjects, 15 had a 10% fall in FEV1 after exercise significant for EIB.Demographic characteristics (gender, age and ethnicity) were not different comparing subjects with EIB to those without EIB.There was a significant correlation between spirometry and IOS measurements at baseline, 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes and post bronchodilator after exercise (r= -0.75, -0.72, -0.72, -0.76, -0.75, -0.72 and -0.75 respectively, p<0.01) in asthmatic subjects without EIB.In asthmatic subjects with EIB, there was a significant correlation between spirometry and IOS measurements at baseline, 1 minute, and post bronchodilator after exercise (r=-0.55,-0.79 and -0.63 respectively p<0.05).There was weak correlation between spirometry and IOS measurements at 5 minutes, 10 minutes, 15 minutes and 20 minutes after exercise for asthmatic subjects with EIB. Conclusion:A significant correlation was found between spirometry and IOS measurements of change in airway function in asthmatic patients both with EIB and without EIB.
Omics
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Exercise causes bronchoconstriction in asthmatic subjects, which is usually followed by a refractory period during which exercise of the same intensity will cause less bronchoconstriction. This study examined the role of contractile prostaglandins in the initial bronchoconstriction after exercise and the role of inhibitory prostaglandins in the refractoriness after exercise. Subjects were pretreated with indomethacin, 50 mg twice daily, on 1 occasion or placebo on 2 occasions for 3 days. This was followed by 2 exercise challenges on a bicycle ergometer at least 30 min apart. Indomethacin did not alter the initial bronchoconstriction after exercise. The maximal fall in FEV1 after the first exercise challenge after placebo was 0.67 +/- 0.17 L and 0.68 +/- 0.17 L, and after indomethacin it was 0.67 +/- 0.12 L. Indomethacin, however, did prevent refractoriness after exercise. The maximal fall in FEV1 after the second exercise challenge after placebo was 0.31 +/- 0.06 L and 0.36 +/- 0.12 L, and after indomethacin it was 0.64 +/- 0.12 L. These results indicate that indomethacin pretreatment does not alter bronchoconstriction after exercise, and they also indicate that indomethacin pretreatment prevents refractoriness after exercise in asthmatic subjects.
Exercise-induced asthma
Physical exercise
Bicycle ergometer
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Exertional dyspnea is a common clinical problem seen with different etiologies in different clinical situations and may even be found in healthy individuals. Approximately 90% of asthmatic patients suffer from shortness of breath in the context of exercise. Dyspnea, occurring during or after exercise, can be the only clinical manifestation of asthma. On the other hand, bronchoconstriction may occur in the absence of asthma - so-called exercise-induced bronchoconstriction. In elite athletes and persons performing sports with high ventilatory demand, bronchospasm in the context of exercise may appear without the presence of asthma. In these circumstances, bronchoconstriction is characterized by neutrophilic inflammation in the bronchial epithelium. Exercise-induced bronchoconstriction in the absence of asthma is difficult to diagnose and to treat. Diagnostic tests are often complex to handle, infrequently performed and the majority miss well-defined cut-off points. Diagnosis is confirmed either by performing direct or indirect bronchial challenge tests for classical asthma or through indirect tests for exercise-induced bronchoconstriction. Therapy for both diseases is based on short-acting beta-agonists used 15 min before exercise. Daily basic therapy is different for asthmatics and nonasthmatics - where basic therapy consists of inhaled corticosteroids in asthmatics, leukotriene antagonists play a more important role in exercise-induced bronchoconstriction. In general, treatment of exercise-induced asthma follows the Global Initiative of Asthma guidelines.
Exercise-induced asthma
Physical exercise
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This study describes the result of free-running exercise performed on 40 asthmatic subjects and 40 age and sex matched controls. A percentage fall of more than 15% in PEFR was used for the diagnosis of exercise-induced asthma (EIA). 77.5% of our asthmatic patients had exercise-induced bronchoconstriction (EIB) while none of the control subjects exhibited EIB. Twenty-seven patients gave positive history of EIA out of which 25 (92.59%) had positive exercise testing. Conversely, 13 patients with asthma did not give history of EIA but 6 of this (46.15%) were found to have EIB on exercise. History alone is therefore insufficient to diagnose patients with exercise-induced asthma.
Exercise-induced asthma
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To evaluate the preventive effect of inhaled ipratropium powder on low-grade bronchoconstriction elicited by breathing cold air during exercise, we subjected 10 adult patients with mild asthma to four identical treadmill exercise tests. The temperature of inhaled air during exercise was -9 +/- 1 degree C. Sixty minutes before exercise, the patients inhaled either placebo or 0.2, 1, or 2 mg of ipratropium powder according to a cross-over, double-blind arrangement. The mean post-exercise fall from the post-treatment pre-exercise values in the four treatment groups was 14, 14, 16 and 16% for FEV1, and 59, 52, 52 and 55% for SGaw, respectively. We concluded that doses of ipratropium up to 20-50 times higher than those known to have a marked effect on resting bronchomotor tone in clinically stable asthma did not blunt the bronchoconstriction response following exercise with cold air breathing in our patients with mild asthma.
Ipratropium
Exercise-induced asthma
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