Pretreatment of exercise-induced asthma in adults with aerosols and pulverized tablets. A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma. Effect of inhaled disodium cromoglycate and albuterol on energy cost of running in asthmatic children. Comparison of the effects of inhaled calcium antagonist verapamil, sodium cromoglycate and ipratropium bromide on exercise-induced bronchoconstriction in children with asthma. Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma. Inhibition of exercise-induced asthma by different pharmacological pathways. Suppression of exercise-induced asthma by salbutamol, theophylline, atropine, cromolyn, and placebo in a group of asthmatic children. The protective effect of inhaled terbutaline, sodium cromoglycate and budesonide on exercise-induced asthma in children. A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise-induced bronchospasm. Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma. Exercise-induced bronchoconstriction as an expression of bronchial hyperreactivity: a study of its mechanisms in children. Duration of protective effect of terbutaline sulfate and cromolyn sodium alone and in combination on exercise-induced asthma. Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children. Pretreatment of exercise-induced asthma by disodium cromoglycate and fenoterol. Effect of fenoterol hydrobromide and sodium cromoglycate individually and in combination on postexercise asthma. Pretreatment of exercise-induced asthma in children using disodium cromoglycate and fenoterol inhalation powder. Prevention of exercise-induced asthma by drugs inhaled from metered aerosols. Preventive effect and duration of action of disodium cromoglycate and procaterol on exercise-induced asthma in asthmatic children. [Stress-induced asthma--placebo-controlled double-blind comparison of prevention using fenoterol, disodium cromoglycate and a combination of the two]. [Effectiveness of disodium cromoglycate, salbutamol, and ipratropium bromide in the inhibition of exercise-induced bronchospasm].
Eighteen adult asthmatics took part in a double-blind crossover study comparing the effect on exercise-induced asthma (EIA) of pretreatment with aerosolized 1) disodium cromoglycate (DSCG), 2) ipratropium bromide (IPTB), 3) fenoterol, 4) DSCG + IPTB and 5) saline. EIA was completely blocked by pretreatment with the beta 2-agonist, fenoterol. The protective effect of nebulized DSCG and IPTB given alone could not be distinguished from that of isotonic saline. The combination of DSCG and IPTB reduced the post-exercise bronchoconstriction more than any of the two drugs given separately. Thirteen of the 18 patients went on to a double-blind cross-over study of the effect on EIA of pretreatment with the usually recommended dosages off salbutamol, theophylline and their combination administered as pulverized tablets. Seven patients were withdrawn from this part of the study because of side-effects, and in the remaining six none of the oral pretreatments could be distinguished from placebo, despite serum theophylline concentrations within or above the commonly recommended therapeutical range. Exercise-induced asthma (EIA) was provoked by a standardized treadmill running for 8 min in seven atopic adult asthmatics. The tests were performed using a double-dummy technique after placebo, oral ketotifen, inhaled clemastine, ipratropium bromide and sodium cromoglycate (SCG), in a random single blind-fashion on different days. The mean post-exercise percentage fall in forced expiratory volume in 1 sec (FEV1) was 47 (s.e. 6.95), 39 (s.e. 8.35), 27 (s.e. 7.17), 23 (s.e. 7.69) and 7.0 (s.e. 4.62)% respectively. There was significantly less mean bronchoconstriction with SCG (P less than 0.01), ipratropium bromide and clemastine (P less than 0.05) but not with ketotifen. Six out of seven individual patients had significant protection of EIA with sodium cromoglycate, four with ipratropium bromide, three with clemastine but only one with ketotifen. Ipratropium bromide and clemastine were bronchodilators at rest, whereas SCG and ketotifen were not. Despite its claims to work as a mast cell stabilizing drug, ketotifen in a single dose does not have an effect similar to sodium cromoglycate in EIA, nor does it compare with inhaled clemastine or ipratropium bromide. The purpose of this study is to evaluate the effect of disodium cromoglycate and albuterol on energy cost of running, gas exchange, and ventilation during maximal exercise in children with exercise-induced asthma (EIA). Twelve children (7.1-15.5 years old) with a history of mild to moderate asthma and EIA performed three maximal exercise tests on a treadmill: 1) test A, without premedication; 2) test B, after premedication with inhaled disodium cromoglycate (DSCG) (40 mg); 3) test C, after premedication with inhaled albuterol (200 micrograms). The energy cost of running was calculated at each minute of exercise. None of the children were limited by dyspnea during the run. The post-exercise fall in FEVi after test A was greater than 20% for each child, the mean fall being 32.8 +/- 11.6%, in comparison with 12.6 +/- 8.9% after test B (P less than 0.001) and 2.5 +/- 5.3% after test C (P less than 0.001). There was no difference in the baseline oxygen uptake for the three tests. Maximum oxygen uptake (VO2 peak) decreased from 43.9 +/- 7.7 mL/min/kg in test A to 37.7 +/- 6.0 mL/min/kg in test B (P less than 0.01) and 39.1 +/- 7.2 mL/min/kg in test C (P less than 0.05). Ventilatory anaerobic threshold in tests B and C was significantly lower than in test A (P less than 0.01). Ventilation (L/min) and energy cost of running (O2 mL/kg/m) were significantly lower in tests B and C than in test A at comparable times. Running time was longer in B and C (P less than 0.05) with respect to A.(ABSTRACT TRUNCATED AT 250 WORDS) Fifteen children with exercise-induced asthma (EIA) participated in a double-blind trial comparing the protective effects of inhaled sodium cromoglycate (20 mg/2 ml), ipratropium bromide (500 micrograms/2 ml) and verapamil (5 mg/2 ml). Saline was used as control. There was no significant difference in base line pulmonary function before and after the administration of each agent. After exercise the maximal percentage fall in the forced expiratory volume in 1 s (FEV-1) (means and SD) were 40.9 +/- 17.2 after inhalation of saline, 15.3 +/- 11.7 after sodium cromoglycate, 36.2 +/- 21.4 after verapamil and 21.7 +/- 17.7 after ipratropium bromide. The inhibitory effects of sodium cromoglycate and ipratropium bromide were significant whereas verapamil failed to produce any effect. To see if a double dose of verapamil is more effective, nine different children with EIA were provoked by the same standardized treadmill running after giving a placebo (4 ml saline) and after verapamil (10 mg in 4 ml). Despite the double dose, again verapamil was ineffective even though the protection index doubled that obtained with the lower dose. The results suggest that the calcium antagonist (verapamil) had almost no effect on the prevention of EIA in the children studied. Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate, reproterol, sodium cromoglycate plus reproterol, and placebo in exercise-induced asthma. Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited exercise-induced asthma. The best protection is effected by the combination of sodium cromoglycate and reproterol. A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive. Exercise-induced asthma (EIA) was provoked by standardized treadmill running for 6 minutes in 15 asthmatic children. The tests were carried out after the administration of a placebo, salbutamol, sodium cromoglycate, choline theophyllinate, and atrophine methonitrate aerosol in randomized fashion on different days. The mean post-exercise percent fall in peak expiratory flow rate was 45-2, 4-1, 19-6, 18-3, and 24-9 respectively. The proportion of children having significant amelioration of their EIA compared with those taking the placebo was 100% for salbutamol, 80% for cromoglycate and theophyllinate, and 60% for atropine. Salbutamol, choline theophyllinate, and atropine were bronchodilators at rest whereas cromoglycate was not, and the ability to suppress EIA was unrelated to bronchodilator effect. Even after bronchodilatation at rest, further broncho-dilatation occurred during the exercise period. A number of drugs are known to inhibit exercise-induced asthma (EIA), but the results in some cases have been difficult to interpret due to the techniques employed. A comparative study was carried out in a group of children to investigate the effects of salbutamol, choline theophyllinate, cromolyn sodium, atropine, and placebo. The exercise test took the form of six minutes of standardized treadmill running. All the drugs, but not the placebo, were able to inhibit EIA ti a significant degree, the effect being most marked with salbutamol. Cromolyn sodium caused no bronchodilatation at rest, while all the other drugs were brondhocilators, the effect being most marked with the atropine during exercise. It was impossible to distinguish the type of drug used for inhibition of EIA if it caused bronchodilatation at rest. The manner in which an exercise test can be used to investigate the duration of action or site of action of drugs is noted. The effect of single-dose inhaled terbutaline, sodium cromo-glycate and budesonide were compared with control in 11 exercise-induced asthma (EIA) patients, aged 9-14 years. Patients exercise for 6 minutes, 15 minutes after inhaling drugs. The FVC, FEV1, PEFR and MMEF were recorded before exercise and after exercise at 5 minutes interval up to 25 minutes. After exercise, the mean (SEM) maximal percentage fall in FEV1 after placebo, 200 micrograms of terbutaline, 10 mg of sodium cromoglycate, and 100 micrograms of budesonide were 22.81 (3.45), 4.05 (2.11), 11.29 (1.18), and 20.36 (2.33) respectively. It was concluded that single-dose inhaled terbutaline and sodium cromoglycate resulted in a significant protective effect on exerxide-induced asthma whereas budesonide did not. Inhaled albuterol and cromolyn by spinhaler have both been shown to be effective in the treatment of exercise-induced bronchospasm. Eighty subjects with exercise-induced bronchospasm participated in a randomized parallel group study comparing albuterol (180 microgram) and cromolyn (20 mg) administered 15 minutes prior to a standardized treadmill challenge. The cromolyn group was restudied after 2 and 4 weeks of 4 times/day cromolyn therapy. The albuterol group was also studied at 2 and 4 weeks, but they only used their inhaler as needed between study visits. The mean maximum FEV1 drop post-exercise in the albuterol group improved from 33% (screening visit) to 6% (treatment day 1). The cromolyn group showed significantly less (P less than .01) improvement than the albuterol group (31% drop at the screening visit to 14% drop at treatment day 1). When 2 or 4 weeks of continuous cromolyn therapy was given in addition to a dosage 15 minutes prior to exercise, there was no significant difference compared with acute cromolyn administration alone. In summary, acute administration of albuterol was better prophylaxis for exercise-induced bronchospasm than acute or chronic cromolyn treatment. nan The mechanism of exercise-induced bronchoconstriction (EIB) was studied by observing the protective effects of several aerosol agents in a double-blind, randomised trial. Exercise-induced bronchoconstriction was not affected by placebo, but was reduced by each agent used (p less than 0.001). Blocking the parasympathetic system had the weakest effect, while beta 2 adrenergic stimulation produced the strongest effect which was significantly different from the parasympatholytic (p less than 0.02). The effect of the mast cell stabilizer, sodium cromoglycate (SCG) was found to be intermediate. However in some patients SCG had a stronger effect than the beta 2 adrenergic agonist. A relationship was found between EIB and bronchial hyperreactivity induced by histamine (p less than 0.05). For subjects with EIA participating in physical activities throughout the day, prolonged duration of protection is desirable. The purpose of this study was to determine whether in EIA a combination of the recommended aerosol doses of the beta 2-adrenergic receptor agonist, terbutaline sulfate (0.5 mg), and cromolyn sodium (disodium cromoglycate; 2 mg) provides longer protection against EIA than either drug alone. On four separate days, following the administration of either placebo, terbutaline alone, cromolyn sodium alone or terbutaline and cromolyn sodium together, 12 subjects (seven men and five women; aged 18 to 28 years) with EIA performed four identical eight minute treadmill runs, each separated by two-hour intervals. Drug treatments were given double-blind, with the order counterbalanced using a Latin-square design. Pulmonary function was recorded before the drug, immediately before and after exercise, and at 3, 4, 5, 6, 7, 10, 15, and 30 minutes after exercise. Inspired ventilation, heart rate, and environmental conditions were monitored during exercise. A two-way analysis of variance was performed to investigate the main effects of time and drug treatment. Results indicated that in comparison with placebo, EIA was significantly reduced by either cromolyn sodium or terbutaline administered up to two hours (p less than 0.01) and by the combination (cromolyn sodium and terbutaline) up to four hours after inhalation (p less than 0.05). No significant differences were found between the combination and terbutaline during the initial two hours (p less than 0.5). We conclude that a combination of beta 2-adrenergic receptor agonist and cromolyn sodium is the treatment of choice for prolonged effective protection from EIA. Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone; however, this practice reduces compliance.
                To evaluate the effectiveness of a new pre-combined aerosol formulation (salbutamol and nedocromil) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone.
                Twelve children with asthma were studied in a double-blind, double-dummy, randomized, crossover, placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction. The drugs were delivered by a metered-dose inhaler (salbutamol, 200 microg; salbutamol/nedocromil, 200 microg/4 mg; placebo, 2 puffs) 20 minutes before exercise.
                Both active drugs were significantly more protective than placebo but there was no difference between them. Complete protection was obtained in 12/12, 10/12, and 1/12 subjects for the salbutamol/nedocromil combination, salbutamol alone and placebo, respectively.
                Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction, a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous. This group may represent a subpopulation of subjects who release more, or different, mediators in response to exercise. nan A double-blind trial involving 20 asthmatic patients was carried out to test the effect of fenoterol and sodium cromoglycate alone and in combination on ventilatory function one hour after medication. The results show that fenoterol, whether alone or in combination with sodium cromoglycate, can increase the forced expiratory volume in one second (FEV1) by up to 25% both after rest and after exercise. No patient suffered a decrease in FEV1 using fenoterol, and at least 80% of them recorded an increase in ventilatory ability. Sodium cromoglycate was of no benefit in eliminating early reaction to exercise-induced asthma. The effect of pretreatment with inhalation powder containing fenoterol, sodium cromoglycate, fenoterol plus sodium cromoglycate and placebo, in the prevention of exercise-induced asthma was compared in a randomized, double-blind, cross-over investigation including 17 asthmatic children with exercise-induced asthma. Six minutes of treadmill running was carried out in a climate chamber 30 minutes after pretreatment on the four test days. The post-exercise fall in PEF after pretreatment with fenoterol was 7%, with sodium cromoglycate 20%, with fenoterol plus sodium cromoglycate 6% and after placebo 27%. Both sodium cromoglycate and fenoterol provided protection against exercise-induced asthma (p less than 0.05 and p less than 0.001). Fenoterol gave significantly better protection than sodium cromoglycate (p less than 0.001), and it is concluded that the treatment of choice for the prevention of exercise-induced asthma is the inhalation of a beta 2-agonist. The capacity of salbutamol 0.3 mg (SAL), disodium cromoglycate 3 mg (DSCG), a combination (SAL + DSCG), and ipratropium bromide 80 ug (IB), all given as metered aerosols to prevent exercise-induced (EIA), was compared with that of a placebo, a peroral lactose pill. Seven children participated, having reproducible EIA provoked by running on a treadmill at a heart rate of 170 sustained for 6 min. FEV1 and volume of trapped gas (VTG), defined as the air volume released during rebreathing oxygen with maximum breaths at the end of a multiple breath nitrogen wash out, were used as tests of spasm in large and small airways. SAL and SAL + DSCG offered complete protection in large and small airways. DSCG and IB prevented EIA in large airways (FEV1) to 95%, but only to about 50% in small airways (VTG). SAL or SAL + DSCG gave significantly better protection (FEV1 and VTG) than DSCG and IB (P less than 0.01). Differences between DSCG and IB were not statistically significant. DSCG or propellant caused significant irritation and spasm in small airways (VTG) before exercise. Most subjects seemed to obtain satisfactory protection against EIA by beta 2-agonists. We evaluated the preventive effect and duration of action of disodium cromoglycate (DSCG) and procaterol nebulizer solutions on exercise-induced asthma (EIA) in 14 asthmatic patients. Disodium cromoglycate solution prevented EIA one hour after inhalation in 11 out of 14 (78.6%), and in some patients after four (36.5%) and eight hours (15.4%). The preventive effect and duration of action of DSCG depended on the severity of EIA in each subject. Procaterol solution had a greater effect than DSCG at any time point in the study. With both drugs, however, the effect decreased four and eight hours after inhaling and was related to the severity of the EIA. nan Forty-nine asymptomatic asthmatic children who showed exercise induced bronchospasm (EIB), received in a randomized double-blind fashion one of the four following drugs administered through nebulizer and facial mask: salbutamol 4 mg (13 patients), disodium chromoglycate 20 mg (12 patients), ipratroprium bromide 0.4 mg (12 patients), placebo (12 patients). They performed exercise fifteen minutes after receiving the drugs and spirometries were done 0, 5, 10, 15 and 20 minutes after the end of the exercise. Bronchodilation was noticed 15 minutes after the administration of salbutamol and ipratroprium bromide but not after cromoglycate or placebo. No patient receiving either salbutamol or cromoglycate had EIB whereas it occurred in 50% of those receiving ipratroprium bromide and 91.6% of those receiving placebo.
In a population of stable asthmatics short acting beta-agonists, mast cell stabilisers, or anticholinergics will provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects. On average, SABAs resulted in more effective attenuation than mast cell stabilisers, while mast cell stabilisers were more effective than anti-cholinergic agents. Combining SABA and mast cell stabilisers may be appropriate in selected cases. The variability in the individual degree of response to these drugs in multi arm trials suggests clinicians and patients work together to identify the most effective prophylactic therapy.