[Pirbuterol and salbutamol aerosol for exercise-induced bronchoconstriction]. Formoterol via Turbuhaler gave better protection than terbutaline against repeated exercise challenge for up to 12 hours in children and adolescents. Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma. The protective effect of inhaled terbutaline, sodium cromoglycate and budesonide on exercise-induced asthma in children. Evaluation of Fluticasone Propionate and Fluticasone Propionate/Salmeterol Combination on Exercise in Pediatric and Adolescent Patients with Asthma [Effectiveness of disodium cromoglycate, salbutamol, and ipratropium bromide in the inhibition of exercise-induced bronchospasm]. Salmeterol and fluticasone in young children with multiple-trigger wheeze. Pretreatment with albuterol versus montelukast for exercise-induced bronchospasm in children. Suppression of exercise-induced asthma by salbutamol, theophylline, atropine, cromolyn, and placebo in a group of asthmatic children. Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction in children. [Prolonged effect against exercise-induced bronchospasm: salmeterol versus sodium cromoglycate]. Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children. A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise-induced bronchospasm. Prevention of exercise induced asthma by inhaled salmeterol xinafoate. Breathlessness and exercise tolerance in chronic airflow obstruction: 2-hourly versus 4-hourly salbutamol by inhalation. Evidence of the Rapid Protective Effect of Formoterol Dry-Powder Inhalation against Exercise-Induced Bronchospasm in Athletes with Asthma Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Effects of nedocromil and salbutamol on airway reactivity in children with asthma Comparative effects of long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. Inhaled formoterol in the prevention of exercise-induced bronchoconstriction in asthmatic children. Protection against cold air and exercise-induced bronchoconstriction while on regular treatment with Oxis. Inhaled and oral bronchodilator therapy in exercise induced asthma. Effects of inhaled budesonide alone and in combination with low-dose terbutaline in children with exercise-induced asthma. The duration of protection from exercise-induced asthma by inhaled salbutamol, and a comparison with inhaled reproterol. Effects of montelukast and salmeterol on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction. Comparative Efficacy of Salbutamol and Salmeterol in Exercise-Induced Asthma Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma. An Evaluation of Levalbuterol HFA in the Prevention of Exercise-Induced Bronchospasm Airway tone during exercise in healthy subjects: effects of salbutamol and ipratropium bromide. Combined treatment with ipratropium bromide and beta-2-adrenoceptor agonists in childhood asthma. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses. Protective effect and duration of action of formoterol aerosol on exercise-induced asthma. Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group. Aerosolized clenbuterol (NAB 365) and salbutamol in exercise-induced asthma. Effect of oral terbutaline on exercise-induced asthma. Albuterol aerosol versus albuterol Rotacaps in exercise-induced bronchospasm in children. Beta 2-agonists and running economy in prepubertal boys. A comparison of terbutaline inhaled by Turbuhaler® and by a chlorofluorocarbon (CFC) inhaler in children with exercise‐induced asthma [Efficacy of broxaterol (vs salbutamol) in asthma induced by physical exercise in children]. Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm. Prevention of exercise-induced bronchospasm in asthmatic children. Effect of aerosol and oral procaterol hydrochloride. Time-effect of montelukast on protection against exercise-induced bronchoconstriction. Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm. Double-blind pretreatment of exercise-induced asthma with sequential inhalations of fenoterol from an aerosol and as a powder (second of two parts). Effects of salbutamol, ipratropium bromide and disodium cromoglycate on breathlessness induced by exercise in normal subjects. Bricanyl® Turbuhaler® and Ventolin® Rotahaler® in exercise‐induced asthma in children Oral Montelukast Compared with Inhaled Salmeterol To Prevent Exercise-Induced Bronchoconstriction Salmeterol versus sodium cromoglycate for the protection of exercise induced asthma in children--a randomised cross-over study. Oxitropium bromide, ipratropium bromide and fenoterol in exercise-induced asthma. Effects of albuterol and procaterol on exercise-induced asthma. Comparison between Bricanyl Turbuhaler and Ventolin metered dose inhaler in the treatment of exercise-induced asthma in adults. Effect of long-term salmeterol treatment on exercise-induced asthma. Does single dose salmeterol affect exercise capacity in asthmatic men? Comparative efficacy of salbutamol, ipratropium, and cromoglycate in the prevention of bronchospasm induced by exercise and hyperosmolar challenges. Prevention of Exercise-induced Bronchospasm in Pediatric Asthma Patients: A Comparison of Two Salmeterol Powder Delivery Devices Albuterol HFA is as effective as albuterol CFC in preventing exercise-induced bronchoconstriction. The effect of regular inhaled albuterol on exercise-induced bronchoconstriction. Proventil HFA prevents exercise-induced bronchoconstriction in children. Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma. Comparative effects of caffeine and albuterol on the bronchoconstrictor response to exercise in asthmatic athletes. Exercise-induced bronchospasm: evaluation of albuterol aerosol. Platelet activation during exercise induced asthma: effect of prophylaxis with cromoglycate and salbutamol. The cardiorespiratory response to submaximal exercise in subjects with asthma following pretreatment with controlled release oral salbutamol and high-dose inhaled salmeterol. The pharmacologic effect of aerosolized terbutaline sulfate in exercise-induced bronchospasm. The effect of terbutaline in exercise-induced asthma. Prevention of exercise‐induced asthma by drugs inhaled from metered aerosols Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction. Bronchodilation and inhibition of induced asthma by adrenergic agonists Salmefamol and Salbutamol in exercise-induced asthma in children. Aminophylline vs. salbutamol in exercise-induced asthma. Bitolterol mesylate in exercise-induced asthma. Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children. Fluticasone propionate/salmeterol and exercise-induced asthma in children with persistent asthma. Fenoterol in exercise-induced asthma. Effect of dose on efficacy and duration of action. Prevention of exercise-induced bronchospasm in pediatric asthma patients: a comparison of salmeterol powder with albuterol. Bronchodilator activity of a new inhaled beta 2-adrenoceptor agonist, tulobuterol and its protective effect in exercise-induced asthma. Efficacy and duration of salmeterol powder inhalation in protecting against exercise-induced bronchoconstriction. Plasma cyclic AMP levels in response to exercise and terbutaline sulphate aerosol in normal and asthmatic subjects. Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin. Effect of fluticasone/salmeterol administered via a single device on exercise-induced bronchospasm in patients with persistent asthma. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Comparison of the effects of inhaled SCH 1000 and fenoterol on exercise-induced bronchospasm in children. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. Formoterol provides long-lasting protection against exercise-induced bronchospasm. Inhaled Terbutaline Administered via a Spacer Fully Prevents Exercise-Induced Asthma in Young Asthmatic Subjects: A Double-Blind, Randomized, Placebo-Controlled Study Comparison of the protective effect and duration of action of orally administered clenbuterol and salbutamol on exercise-induced asthma in children. Pretreatment of exercise-induced asthma in children using disodium cromoglycate and fenoterol inhalation powder. Use of serial exercise tests to assess the efficacy and duration of action of drugs for asthma Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge. The effects of oral doses of theophylline and fenoterol on exercise-induced asthma. Effectiveness of terbutaline and theophylline alone and in combination in exercise-induced bronchospasm. Rimiterol and the prevention of exercise-induced asthma. Protective effect and duration of action of inhaled formoterol and salbutamol on exercise-induced asthma in children. Salbutamol and ipratropium bromide solution in the treatment of bronchospasm in asthmatic children. A randomized, double-blind, single-dose, crossover clinical trial of the onset and duration of protection from exercise-induced bronchoconstriction by formoterol and albuterol. Inhaled and oral salbutamol in exercise-induced asthma. Pretreatment of Exercise‐Induced Asthma in Adults with Aerosols and Pulverized Tablets Prophylaxis of exercise-induced asthma with inhaled formoterol, a long-acting beta 2-adrenergic agonist. A new bronchodilating agent, procaterol, in preventing exercise-induced asthma. Evaluation of Reproterol's Effectiveness in Preventing Exercise-Induced Bronchospasm in Children Oral and inhaled salbutamol in the prevention of exercise-induced bronchospasm. Evaluation of Duovent in the prevention of exercise-induced asthma.
Exercise-induced bronchoconstriction was produced in 12 asthmatic patients after a 6 minutes run on a 10 % steep treadmill ergometer . FEV1 decreased by 12 - 73 % ( average 27 % ) of the control value measured before the run . The rather severe exercise-induced bronchoconstriction remained constant for 10 - 20 minutes after the run . 21 minutes after the run two puffs of a bronchodilator ( salbutamol 0.2 mg or pirbuterol 0.4 mg ) were inhaled in an open r and omized cross-over fashion at intervals of 1 to 3 days . Following both bronchodilators FEV1 returned to the control value within 5 minutes . There was no significant difference between the bronchodilating effect of salbutamol versus pirbuterol . Furthermore , no significant differences were observed in pulse rates after inhalation of the two selective beta-2-stimulators . In our trial both pirbuterol and salbutamol seemed to be well tolerated ; side effects were not observed for either drug We aim ed to compare the protective effect of single doses of 4.5 and 9 microg of formoterol fumarate ( F ) , 0.5 mg terbutaline sulphate ( T ) and placebo ( P ) , all via Turbuhaler , against exercise-induced bronchoconstriction ( EIB ) in children . Twenty-seven asthmatic children , showing a fall of > or = 20 % in FEV1 after a st and ardized exercise challenge test ( ECT ) combined with cold air ( -10 degrees C ) inhalation , were r and omized in this cross-over , double-blind study . They had a mean age of 12.6 years ( range 8 - 17 years ) , mean baseline FEV1 90 % ( 73.9 - 105.6 % ) of predicted normal value . Seventeen children used inhaled glucocorticosteroids ( 120 - 750 microg day(-1 ) ) . ECTs were performed 15 min and 4 , 8 , and 12 h after drug administration . F significantly reduced the fall in FEV1 after ECT to 5.4 % ( 15 min ) , 5.2 % ( 4 h ) , 8.2 % ( 8 h ) and 9.3 % ( 12 h ) after 4.5 microg , and 2.5 % , 3.0 % , 5.0 % and 5.4 % after 9 microg , compared with a fall of 18.4 % , 15.7 % , 15.6 % and 16.5 % in FEV1 after P. The fall after T was 3.3 % , 11.6 % , 14.4 % and 19.1 % after 15 min , 4 , 8 and 12 h respectively . The difference between F and T was statistically significant from 4 h and onward ( P-value for all comparisons < 0.05 ) . Children using a single dose of either formoterol Turbuhaler 4.5 or 9 microg had significantly better bronchoprotection against repeated exercise challenge up to 12 h compared with placebo and from 4 h onward compared with terbutaline Turbuhaler 0.5 mg 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 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 result ed in a significant protective effect on exerxide-induced asthma whereas budesonide did not Objective : This study was design ed to demonstrate that four weeks of fluticasone propionate ( FP ) 100 micrograms ( mcg ) combined with salmeterol 50 mcg twice daily ( BID ) via DISKUS ® result ed in protection against bronchospasm induced by activity , as measured by st and ardized exercise challenge testing in pediatric and adolescent subjects who required regular use of inhaled corticosteroids for the treatment of persistent asthma . Methods : Prior to study entry , all patients reported regular use of inhaled corticosteroids ( ICS ) . During screening all patients demonstrated ≥20 % fall in FEV1 following exercise . Results : A total of 231 subjects aged 4 to 17 were r and omized to the two study treatments : 113 to the FP/salmeterol combination group ( FSC ) and 118 to receive FP 100 mcg BID . Of the subjects r and omized , 106 ( 94 % ) subjects in the FSC 100/50 group and 108 ( 92 % ) subjects in the FP 100 group completed the study . At the end of treatment ( Week 4 ) , both FSC and FP  protected against a fall in FEV1 following exercise in patients who at baseline experienced ≥20 % fall in FEV1 following exercise . A mean decrease in FEV1 of 9.9 % was observed in the FSC 100/50 group as compared with a mean decrease of 11.1 % in the FP 100 group ; there was no statistical difference between treatments . Conclusion : Both FSC 100/50 and FP 100 provided protection against an exercised-induced fall in FEV1 ; but statistically significant differences we not noted . Both treatments were well-tolerated over four weeks and FSC 100/50 had an adverse event profile comparable to that observed with FP 100 Forty-nine asymptomatic asthmatic children who showed exercise induced bronchospasm ( EIB ) , received in a r and omized 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 BACKGROUND Treatment guidelines recommend using an inhaled corticosteroid ( ICS ) plus a long-acting β(2)-agonist ( LABA ) for childhood asthma when the symptoms are not controlled by ICS alone , but the appropriate use of LABAs in children continues to be debated . OBJECTIVE To compare the efficacy of an inhaled salmeterol and fluticasone propionate combination , 50/100 μg twice daily , with fluticasone propionate , 100 μg twice daily , or salmeterol , 50 μg twice daily , in children with multiple-trigger wheeze . METHODS A total of 105 children 4 to 7 years of age with multiple-trigger wheezing based on respiratory symptoms and bronchodilator responsiveness and /or exercise-induced bronchoconstriction without a viral cold were r and omized to salmeterol-fluticasone , fluticasone propionate alone , or salmeterol alone via a metered-dose inhaler and a spacer device for 8 weeks . The primary efficacy outcome was exhaled nitric oxide level . Secondary outcomes were lung function measurements via impulse oscillometry , respiratory symptoms , and rescue medication use . RESULTS The exhaled nitric oxide levels decreased after all treatments , significantly more so after salmeterol-fluticasone and fluticasone than with salmeterol ( adjusted geometric means at 8 weeks : salmeterol-fluticasone , 9.4 ppb ; fluticasone , 9.3 ppb ; salmeterol , 13.9 ppb ; salmeterol-fluticasone vs salmeterol , P = .02 ; fluticasone vs salmeterol , P = .01 ) . No treatment differences were found with respect to respiratory symptoms or median rescue use . Salmeterol-fluticasone result ed in a small but statistically significant improvement in baseline lung function compared with fluticasone . All treatments were equally well tolerated . CONCLUSION The effects of salmeterol-fluticasone and fluticasone were comparable , although lung function improvement was better with salmeterol-fluticasone than with fluticasone alone . There is no obvious benefit in initiation therapy with salmeterol-fluticasone rather than fluticasone alone in the treatment of steroid-naive children with multiple-trigger wheeze . TRIAL REGISTRATION Pathway of clinical trial registry of Helsinki University : http://www.hus.fi/?Path=1;28;2530;9899;9900;23618;23903;33578 STUDY OBJECTIVES To compare pretreatment with albuterol versus montelukast added to the current asthma regimen for protection against exercise-induced bronchospasm in children with mild-to-moderate asthma , and to determine whether cysteinyl leukotriene ( Cys-LT ) concentrations measured in the exhaled breath condensate correlated with response to montelukast . DESIGN Prospect i ve , r and omized , double-blind , double-dummy , crossover study . SETTING Asthma clinic at a university-affiliated medical center . PATIENTS Eleven children aged 7 - 17 years with physician-diagnosed mild-to-moderate asthma for at least 6 months and with self-reported exercise-induced bronchospasm ( defined as > or = 15 % decrease in forced expiratory volume in 1 sec [ FEV(1 ) ] at screening and baseline visit ) . INTERVENTION Patients were r and omly assigned to receive 3 - 7 days of oral montelukast 5 - 10 mg/day or 2 puffs of an albuterol metered-dose inhaler just before an exercise challenge and then were crossed over to the alternate therapy for the last visit . MEASUREMENTS AND MAIN RESULTS Serial spirometry was performed before and at 0 , 5 , 10 , 15 , 30 , 45 , and 60 minutes after the exercise challenge at each visit . Measurement of exhaled breath condensate was performed at the screening visit and study visits 1 and 2 . The primary outcome was the maximum change in FEV(1 ) after exercise . Secondary outcomes were the area under the curve for FEV(1 ) ( expressed as percentage decrease from baseline ) during the first 60 minutes ( AUC(0 - 60 ) ) after exercise and the proportion of patients in whom exercise-induced bronchospasm was prevented ( defined as < 15 % decrease in FEV(1 ) after exercise challenge ) . The mean + /- SD maximum decrease in FEV(1 ) was 27.5 + /- 7.9 % at baseline . Patients receiving montelukast had an 18.3 + /- 13.7 % decrease in FEV(1 ) compared with 0.7 + /- 1.6 % in patients receiving albuterol ( p=0.002 , paired t test ) . Exercise-induced bronchospasm was prevented in 100 % of the patients receiving albuterol compared with 55 % receiving montelukast ( p<0.05 , McNemar 's test ) . The AUC(0 - 60 ) was significantly smaller with albuterol compared with montelukast ( p<0.001 , Wilcoxon signed rank test ) . No correlations were found between Cys-LT concentration and the severity of exercise-induced bronchospasm or the response to montelukast .  CONCLUSION Pretreatment with albuterol is more effective than montelukast for prevention of exercise-induced bronchospasm in children with asthma 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 st and ardized 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 BACKGROUND Exercise-induced bronchoconstriction ( EIB ) is common , particularly in children . OBJECTIVES To compare the protective effect of single doses of formoterol fumarate via Aerolizer with placebo and albuterol in children with EIB . METHODS In this r and omized , double-blind , double-dummy , crossover trial , 23 children ( aged 4 - 11 years ) received formoterol , 12 or 24 microg ; albuterol , 180 microg ; or placebo at 4 separate visits . Protection against EIB was evaluated as the maximum percentage decrease in forced expiratory volume in 1 second ( FEV1 ) from the preexercise value after exercise challenge tests ( 6-minute treadmill ) conducted 15 minutes and 4 , 8 , and 12 hours after administration of the dose . RESULTS The maximum percentage decrease in FEV1 after the 4-hour exercise test ( primary efficacy variable ) was significantly less for formoterol , 12 and 24 microg , vs placebo ( P < .001 for both ) or albuterol ( P = .016 and .010 , respectively ) ; albuterol was not significantly different from placebo . Formoterol , 12 and 24 microg , differed from placebo at 8 hours ( P = .002 and .001 , respectively ) , with a smaller difference between albuterol and placebo ( P = .045 ) . Rescue medication use and a high dropout rate may have biased treatment differences at later time points . Protection against EIB ( < 20 % maximum decrease in FEV1 ) across all time points was observed for 17 ( 77 % ) of 22 and 17 ( 74 % ) of 23 children with formoterol , 12 and 24 microg , respectively , compared with 8 ( 35 % ) of 23 with albuterol and 6 ( 27 % ) of 22 with placebo . CONCLUSIONS Single doses of formoterol , 12 or 24 microg , are effective in protecting against  EIB in children , affording a statistically significantly greater protective effect than placebo or albuterol Nineteen subjects with isolated exercise-induced asthma ( FEV1 , FEF25 - 75 % , PEFR , FVC greater than 95 % predicted values , fall in FEV1 of at least 15 % after exercise , typical recent symptoms of exercise-induced asthma , no other treatment ) were entered in a multicenter trial carried out in a double blind , double placebo , cross-over manner . After a one-month baseline period , subjects underwent an exercise after inhaling 100 micrograms of salmeterol ( n = 12 ) or 40 mg of sodium cromoglycate ( n = 7 ) . Treatments were alternated before the second exercise which took place at least 2 days after the first . Efficacy was assessed by examining changes in FEV1 , FEF25 - 75 % after exercise carried out 30 minutes and 7 hours after administering the treatment by comparison with baseline values ( assessment s done 1 , 10 and 30 minutes after exercise , lowest of three values kept for the analysis of each parameter ) . FEV1 and FEF25 - 75 % were significantly higher 30 minutes after taking salmeterol . Salmeterol was found to be superior to sodium cromoglycate  for all parameters 7 hours after administering the drug . Both treatments were well tolerated . This study confirms that the longer duration of effect of salmeterol and its superiority by comparison with the st and ard treatments of exercise-induced asthma BACKGROUND 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 . OBJECTIVE 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 . METHODS Twelve children with asthma were studied in a double-blind , double-dummy , r and omized , 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 . RESULTS 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 . CONCLUSIONS 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 sub population of subjects who release more , or different , mediators in response to exercise 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 r and omized parallel group study comparing albuterol ( 180 microgram ) and cromolyn ( 20 mg ) administered 15 minutes prior to a st and ardized 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 The effect of inhaled salmeterol xinafoate , a long acting beta 2 agonist , on  exercise induced asthma  was studied in a double blind , crossover , and placebo controlled trial . Thirteen asthmatic children with a fall of at least 15 % in their forced expiratory volume in one second ( FEV1 ) after a st and ard exercise test on a motorised treadmill , on separate days performed the same test 1 , 5 , and 9 hours after a single dose of 50 micrograms salmeterol or placebo .  FEV1 was measured before treatment , and before and for 30 minutes after each exercise test . After placebo the number of children with exercise induced asthma was : 10 at 1 hour , 11 at 5 hours , and 12 at 9 hours . Salmeterol prevented exercise induced asthma in all 13 children studied , at 1 , 5 , and 9 hours . Mean maximum falls in FEV1 after exercise were at 1 hour : salmeterol 2.7 % and placebo 24.6 % , 5 hours : salmeterol 5.3 % and placebo 22.7 % ; and 9 hours : salmeterol 3.4 % and placebo 26.6 % . After salmeterol the mean increase in FEV1 was 17.8 % at 1 hour , 19.6 % at 5 hours , and 19.2 % at 9 hours . Inhaled salmeterol prevents exercise induced asthma and produces significant bronchodilatation for at least 9 hours Breathlessness , exercise tolerance , and spirometry were measured in 12 patients whose major symptom was breathlessness , secondary to severe chronic airflow limitation , during a double-blind crossover comparison of inhaled salbutamol in two dosages ( 200 micrograms 4-hourly and 200 micrograms 2-hourly ) with placebo .  Daily visual analogue scores of breathlessness , exercise tolerance and spirometry were all significantly improved with salbutamol in both dosages compared to placebo . The 2-hourly regimen was superior to the 4-hourly regimen only in terms of exercise tolerance . Walking distance had deteriorated significantly 2 hours after salbutamol on the 4-hourly regimen and was usefully increased by an extra dose of salbutamol on the 2-hourly regimen at the equivalent time , without side-effects . Salbutamol provided considerable symptomatic relief in addition to spirometric improvement in patients with chronic airflow limitation Background : Although formoterol , a new long-acting β2-adrenergic agonist , has a rapid bronchodilating action , no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm ( EIB ) . Aim : The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes . Methods : The protective effect of a formoterol ( 12 µg ) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes ( 13 males , mean age 16.8 years ) , in a double-blind , placebo-controlled , two-period cross-over study . On each treatment day , the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo . Results : Formoterol  induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration ( p = 0.007 and p = 0.004 ) ; placebo treatment had no effect on EIB , the maximum percent fall in FEV1 after exercise being 29.3 ± 14.3 % and 22.9 ± 13.7 % at 15 min and 4 h , respectively . Formoterol offered good protection against EIB in 12 athletes ( 86 % ) who experienced a decrease in FEV1 after exercise < 10 % both 15 min and 4 h after administration . The mean maximum percent fall in FEV1  after formoterol was 5.9±7.2 % at 15 min ( p < 0.0001 ) , and 5.8 ± 6.9 % at 4 h ( p < 0.0001 ) . There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol , nor was the heart rate at the end of exercise significantly different on the 2 treatment days . No side effect was observed in either group . Conclusions : This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing . Furthermore , the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration STUDY OBJECTIVE To compare the acute bronchodilatory effect of the long-acting beta2-agonist formoterol against the short-acting beta2-agonist ( SABA ) terbutaline during exercise-induced bronchoconstriction ( EIB ) in children with asthma . DESIGN A r and omized , double-blind , placebo-controlled , crossover study of the immediate effect of formoterol , 9 microg , vs terbutaline , 0.5 mg , and placebo administered as dry powder at different study days . Exercise challenge test was used as a model of acute bronchoconstriction . PATIENTS Twenty-four 7- to 15-year-old children with persistent asthma . INTERVENTIONS The children performed st and ardized treadmill exercise tests , breathing dry air , with a submaximal workload . Study medication was administered 5 min after exercise if FEV1 dropped > or = 15 % within 5 min after exercise . FEV1 and forced expiratory flows were measured repeatedly until 60 min after dose . RESULTS Formoterol and terbutaline offered a significant acute bronchodilatory effect from 3 min after dose compared with placebo ( p < 0.001 ) . There was no difference between formoterol and terbutaline in FEV1 5 min after dose ( p = 0.15 ) , with a mean increase from each predrug baseline of 62 % of the maximum increase for both . Median times to recovery within 5 % of baseline FEV1 were 5.0 min and 7.4 min for formoterol and terbutaline , respectively ( p = 0.33 ) . CONCLUSION Single-dose formoterol , 9 microg , via dry powder inhaler provided an acute bronchodilatory effect similar to terbutaline during EIB in schoolchildren with persistent asthma . Formoterol is at least as effective as SABA and may be considered an alternative in the treatment of acute bronchoconstriction in school children The purpose of the present study was to assess the degree of protection of inhaled salmeterol against exercise-induced bronchoconstriction ( EIB ) after chronic compared with single dosing in patients with asthma . Twelve patients with exercise-induced asthma took part in a r and omized double-blind crossover study to compare the duration of action of inhaled salmeterol 50 micrograms twice daily for 4 weeks with that of placebo . A st and ardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period . Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo , whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with salmeterol . The percentage fall in FEV1 after exercise challenge at 6 h was ( first dose ) : placebo 34.8 + /- 4.9 % vs. salmeterol 11.9 + /- 2.8 % ( P < 0.05 ) ; ( 4 weeks ) : placebo 32.9 + /- 5.3 % vs. salmeterol 24.0 + /- 4.4 % ( NS ) . These results suggest that tachyphylaxis may develop to the functional antagonism of salmeterol against EIB OBJECTIVES The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma , but tolerance may develop to its bronchoprotective effect . We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily , instead of the usual dose of 50 microg twice daily , in adolescents receiving regular glucocorticoid inhalations . Methods . In a r and omized , double-blind , 2x28-day crossover study , we administered salmeterol ( 50 microg ) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance . Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period . The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise . RESULTS Fourteen subjects with a mean age of 13.1 years completed the study . The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours . After the 28th consecutive daily dose of salmeterol , the bronchoprotective effect was significantly greater than that of placebo at 1 hour , but not at 9 hours . CONCLUSIONS We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours , but that this effect may wane during regular once-daily salmeterol treatment , despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids Nedocromil and salbutamol are effective drugs in preventing  exercise-induced asthma ( EIA ) . The aim of this study was to compare the protective effects of both drugs and a combination of both drugs against cold dry air-induced bronchoconstriction , using cold dry air challenges ( CACh ) as a surrogate for exercise . Twenty-five atopic children ( mean age 13.7 , range 8–18 yrs ) with EIA participated in the study . Lung function tests were performed before medication , 30 min after medication and just before CACh , and 3 and 15 min after the challenge on four consecutive days . CACh consisted of a 4-min isocapnic hyperpnoea of −10 ° C , absolutely dry air . Treatment consisted of nedocromil ( two puffs of 2 mg ) plus placebo , salbutamol ( two puffs of 100 µg ) plus placebo , the combination of both drugs , and placebo alone , in a r and om order . Both active drugs were significantly more protective than placebo and the combination showed an additive effect . Mean maximum postchallenge decrease in forced expiratory volume in one second  after placebo was 27±8.1 % , 12±9.5 % after nedocromil , 8±10.4 % after salbutamol , and 4.5±6.7 % after the combination of both drugs , respectively . These results suggest that both drugs protect against exercise-induced asthma . Although not as effective as salbutamol and combined medication , nedocromil can give sufficient protection for many patients BACKGROUND Exercise-induced asthma ( EIA ) is a common problem that can be controlled with long-acting beta-agonists and leukotriene-modifying compounds . There is , however , limited information on the comparative effectiveness of the two classes of drugs , as well as the relative potencies of the antileukotriene agents . OBJECTIVE The purpose of the present study was to provide data on the above issues . METHODS We performed a r and om-order , blinded , double-dummy , placebo-controlled trial in 10 patients with EIA . Each subject received st and ard single doses of salmeterol , montelukast , zafirlukast , zileuton , and placebo on separate days . The participants performed 4 minutes of cycle ergometry while breathing frigid air 1 , 4 , 8 , and 12 hours after administration of the test agents . The primary endpoint was the extent of the decrement in the FEV(1 ) 10 minutes after exertion . RESULTS With placebo , symptomatic airway narrowing developed at all times ( mean + /- SE decrease in FEV(1 ) ranged between 21 % + /- 5 % and 26 % + /- 5 % ) . Salmeterol acted quickly and significantly blunted the obstructive response for 12 hours ( DeltaFEV(1 ) first hour : 8 % + /- 3 % ; DeltaFEV(1 ) twelfth hour : 8 % + /- 3 % ; P < .0001 vs placebo and P = .72 vs time ) . The leukotriene-modifying agents produced effects within 1 hour of ingestion . Like salmeterol , montelukast and zafirlukast also offered long-lasting protection , and there were no significant differences between them ( montelukast DeltaFEV(1 ) twelfth hour : 9 % + /- 4 % ; zafirlukast DeltaFEV(1 ) twelfth hour : 11 % + /- 2 % ; P = .75 ) or the beta(2)-agonist ( montelukast vs salmeterol : P = .72 ; zafirlukast vs salmeterol : P = .48 ) . Zileuton provided equivalent prophylaxis for the first 4 hours ( DeltaFEV(1 ) fourth hour : 11 % + /- 2 % ) ; however , by 8 hours , it was less efficacious than all of the other active compounds , and by 12 hours it did not differ from placebo ( DeltaFEV(1 ) twelfth hour : 19 % + /- 4 % ; P = .33 ) . CONCLUSIONS Single doses of the currently available leukotriene receptor antagonists provide prompt effective and persistent defense against EIA that equals that seen with a long-acting beta(2)-agonist . The synthesis inhibitor zileuton affords a comparable magnitude of prophylaxis but has a considerably shorter duration of action The duration and magnitude of the effect of inhaled formoterol ( 12 micrograms ) against exercise-induced bronchoconstriction ( EIB ) was compared with that of inhaled salbutamol ( 200 micrograms ) and that of placebo in 15 children with asthma and EIB in a double-blind , double-dummy , within-patient , placebo-controlled study . The treatments were given by metered dose aerosol on three different days . The exercise test was performed at the 3rd and the 12th hour after dosing . The magnitude of the blocking effect was assessed both by evaluating the lowest FEV1 reading obtained within an hour after each exercise test and by considering the percent decrease below the baseline FEV1 measured before drug administration . Comparison of the lowest values obtained during the hour after each exercise test shows that formoterol was significantly better than both salbutamol ( p = 0.022 ) , and placebo ( p = 0.001 ) in limiting exercise-induced bronchoconstriction after the first exercise test ( 3 h after dosing ) , while no difference was observed between salbutamol and placebo ( p = 0.198 ) . After the second exercise test ( 12 h after dosing ) , formoterol again proved to be more effective than both salbutamol ( p = 0.008 ) and placebo ( p = 0.001 ) , and no significant difference was observed between salbutamol and placebo ( p = 0.391 ) . The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests . No adverse effects were reported in any treatment group . The protection against EIB is significantly more prolonged after formoterol than after salbutamol , and persists for 12 h after dosing This study aim ed to compare the duration of protection against exercise-induced bronchoconstriction ( EIB ) after inhalation of formoterol ( Oxis ) Turbuhaler with that of terbutaline Turbuhaler and placebo Turbuhaler in asthmatic patients treated regularly with formoterol Turbuhaler 9 microg b.i.d . and inhaled steroids .  The study . performed at three centres ( Göteborg and Lund , Sweden , and Trondheim , Norway ) , consisted of an open-label part with formoterol Turbuhaler 9 microg b.i.d . and a r and omized , double-blind , cross-over part with a single dose ( on top of the regular treatment ) of either formoterol Turbuhaler 9 microg , terbutaline Turbuhaler 0.5 mg or placebo Turbuhaler . The patients attended the clinic six times : twice for screening visits , three times for r and omized treatment and once for a follow-up visit . Patients received regular b.i.d . treatment with formoterol 9 microg for a mean period of 16 days . Formoterol gave a post-exercise fall of 12 , 10 , 15 and 17 % in forced expiratory volume in 1 sec ( FEV1 ) 15 min , 4 , 8 and 12 h after inhalation . The differences compared with placebo ( falls of 26 , 22 , 23 and 22 % ) and terbutaline ( falls of 17 , 18 , 22 and 22 % ) were all statistically significant ( P<0.05 for all comparisons ) . Patients on regular treatment with formoterol Turbuhaler 9 microg b.i.d . have a significant protection against EIB up to 12 h after inhalation of formoterol 9 microg . The protection was also significantly better than that of terbutaline Turbuhaler 0.5 mg Measurements of peak expiratory flow rate during serial exercise tests were used to assess the efficacy of the beta adrenergic stimulants oral terbutaline ( 5 mg ) and fenoterol aerosol ( 400 micrograms ) , in preventing post-exercise bronchoconstriction in 18 asthmatic subjects . While both compounds significantly elevated resting levels of peak expiratory flow rate for at least four hours , there were qualitative and quantitative differences in the effects of the two drugs on exercise induced bronchoconstriction . Oral terbulation did not significantly alter the pattern of response to exercise . However , the peak expiratory flow rates before during and after exercise were significantly higher compared with placebo at two , four and six hours after the drug . The importance of examination of actual values for peak expiratory flow rates as well as percentage changes when testing oral bronchodilators is emphasised . Aerosol fenoterol completely blocked post-exercise bronchoconstriction immediately after inhalation and for up to four hours in most subjects . Bronchodilatation occurred in all subjects during exercise in the presence of both the active and placebo drugs . It is postulated that the superiority of the aerosol in blocking exercise induced bronchoconstriction may be function of its activity at the surface of the bronchial mucosa The effect of aerosolized terbutaline in a dose of 32.5 micrograms and its placebo , administered in a double-blind fashion , was studied in 14 children with exercise-induced asthma ( EIA ) before and during a 4-wk treatment period with aerosolized steroid ( budesonide , 400 micrograms/day ) . Effects were assessed from the changes in peak expiratory flow ( PEF ) , forced expiratory volume in one second ( FEV1 ) , and forced expiratory flow ( FEF25 - 75 ) before and after treadmill exercise challenge . Compared with placebo there was a significant improvement in pulmonary function after terbutaline . During budesonide therapy , pulmonary function improved further , but there was no enhancement of the response to terbutaline . Terbutaline alone , budesonide plus placebo , and budesonide plus terbutaline reduced the exercise-induced fall in FEV1 by 30 , 51 , and 84 % , respectively . The effect of budesonide on EIA was delayed during the 4 wk of treatment as compared with the improvement in resting pulmonary function . The present results suggest that 1 to 4 wk of therapy with inhaled corticosteroids decreases the severity of EIA . Further , the combined effect of inhaled corticosteroid and beta-2 agonist on pulmonary function appears to be additive beta-Adrenergic bronchodilators can prevent the development of exercise-induced  asthma  ( EIA ) . To investigate the duration of this effect , we determined the time at which the protective effect of salbutamol diminished significantly in six subjects . All had stable asthma known to be triggered by exercise . Following a control exercise test , identical tests were repeated weekly at various times ( 1 - 6 hours ) after inhalation of 200 micrograms of salbutamol . Significant protection ( less than 75 % ) was lost in two subjects at 2 hours , in two at 4 hours and in two at 6 hours . A further exercise test was performed after inhalation of 1 mg of reproterol , at the time when salbutamol no longer afforded significant protection . There was a significantly smaller fall in peak expiratory flow rate after exercise ( P less than 0.01 ) with reproterol than with salbutamol , at the same time after inhalation . There was no relationship between the degree or duration of protection from EIA and the bronchodilator effect of the drugs , the age and sex of the subjects , the length of asthma history or severity of base-line EIA , except perhaps the requirement for regular treatment with a steroid aerosol or sodium cromoglycate STUDY OBJECTIVES To compare the effect of montelukast and the long-acting beta(2)-agonist salmeterol on cardiopulmonary exercise economy and physical performance in adult patients with asthma during exercise . DESIGN AND PATIENTS Asthmatic patients ( n = 18 ) , aged 18 to 35 years with exercise-induced bronchoconstriction ( EIB ) , using a double-blind , double-dummy cross-over design . Montelukast , 10 mg/d , was compared to inhaled salmeterol , 50 microg bid . The study medication was administered for at least 5 days prior to testing , with a washout period of at least 5 days . Treadmill exercise tests ( 5.3 % inclination , -15 degrees C ambient temperature ) were performed at work loads of 80 % of maximal oxygen uptake ( Vo(2)max ) [ 6 min ] , rest ( 4 min ) , 60 % of Vo(2)max ( 6 min ) , and finally step increments until exhaustion . MEASUREMENTS AND RESULTS We investigated parameters of gas exchange , physical performance , and lung function . After montelukast , the oxygen pulse was higher than after salmeterol , at 80 % of Vo(2)max ( p = 0.035 ) , and 6 min at 60 % of Vo(2)max ( p = 0.011 ) . Lung function during exercise , running time to exhaustion , Borg score , lactate levels , Vo(2)max , carbon dioxide elimination , minute ventilation , ventilatory equivalents , respiratory exchange ratio , and heart rate were not significantly different between the two treatments . The maximal postexercise fall in FEV(1 ) from baseline occurred 2 min after run to exhaustion , and was greater after salmeterol than after montelukast : mean , 16.2 % ( SD , 11.0 ) vs 10.0 % ( SD , 12.2 ) [ p < 0.001 ] . CONCLUSIONS In adult asthmatics with EIB , montelukast may have a more favorable effect on the oxygen pulse , thus suggesting improved gas exchange during exercise This study compared the protection provided by salbutamol and salmeterol against exercise-induced asthma . Asthmatic patients ( n = 12 ) with exercise-induced asthma were exercised submaximally for 6 min on a treadmill 1 , 6 and 12 h after inhalation of 200 μg salbutamol or 50 μg salmeterol . Each patient also took baseline exercise 1 h after two puffs of placebo . Two days later the drugs were administered in a double-blind trial of crossover design with an interval of 48 h between the two treatments . The main parameters measured were : air flow with a Wright flowmeter and mediator concentrations ( histamine , leucotriene and prostagl and in D2 measured by radioimmunoassay ) in venous blood , which was withdrawn before and 4 min after each exercise period . The maximum percentage bronchoconstriction recorded following placebo was 29 ± 4 % and following salbutamol inhalation it was 4 ± 4 % , 20 ± 13 % , 27 ± 10 % , respectively , for the exercise periods performed 1 , 6 and 12 h after inhalation of the drug . Following salmeterol , the corresponding figures were 3 ± 4 % , 3 ± 3 % and 11 ± 9 % . The concentrations of mediator in plasma were significantly increased after exercise . Salbutamol and salmeterol intake reduced these concentrations both when the patients were at rest and following the exercise period . This effect of both drugs on the mediators corresponded with the protection they provided against exercise-induced asthma and was maintained for 12 h after salmeterol inhalation and for 6 h after salbutamol inhalation The effect of 5 mg nebulised salbutamol on the cardiorespiratory responses to a progressive maximal exercise test was investigated in eight asthmatic ( mean forced expiratory volume in one second ( FEV1 ) 3.48 ( 1.0 ) litres ) and eight non-asthmatic men . Exercise tests were performed on a bicycle ergometer after administration of nebulised salbutamol or matched saline placebo . In the asthmatic subjects  salbutamol increased the resting FEV1 by 11 % . The mean ( SD ) percentage fall in FEV1 after exercise did not change significantly ( salbutamol 9.4 ( 12.8 ) ; placebo 15.0 ( 8.0 ] , but because the FEV1 before exercise was increased the lowest FEV1 after exercise was also significantly higher after salbutamol than placebo ( 3.60 ( 1.13 ) v 2.85 ( 0.80 ) litres ) . Despite the improvement in FEV1 before exercise there was no significant difference in maximal workload , oxygen uptake , heart rate , or ventilation during exercise after salbutamol compared with placebo in the asthmatic patients .  Tidal volume was higher at maximal exercise after salbutamol but there was no change in perception of breathlessness or exertion in the asthmatic subjects . During submaximal progressive exercise the perceived rate of exertion was reduced in the asthmatic patients and oxygen pulse was reduced in both groups owing to a small and non-significant increase in heart rate . The FEV1 and cardiorespiratory response to the progressive maximal exercise test in the non-asthmatic subjects were otherwise unchanged after salbutamol . The results suggest that 5 mg nebulised salbutamol has little effect on the cardiorespiratory responses to progressive maximal exercise in patients with mild asthma and in non-asthmatic subjects .  Salbutamol in this dose may reduce the severity of exercise induced asthma , but no ergogenic effect on maximal exercise performance was shown Background . Exercise-induced bronchospasm ( EIB ) affects up to 90 % of all patients with asthma . Objective . This study evaluated the ability of levalbuterol hydrofluoroalkane ( HFA ) 90 μg ( two actuations of 45 μg ) administered via metered dose inhaler ( MDI ) to protect against EIB in mild-to-moderate asthmatics . Methods . This was a r and omized , double-blind , placebo-controlled , two-way cross-over study . Patients with asthma ( n = 15 ) were ≥18 years , had a ≥6-month history of EIB , ≥ 70 % baseline predicted forced expiratory volume in 1 second ( FEV1 ) , and a 20 % to 50 % decrease in FEV1 after treadmill exercise challenge using single-blind  placebo MDI . Levalbuterol or placebo was self-administered 30 minutes before exercise . Treatment sequences were separated by a 3-to 7-day washout period . Spirometry was performed predose , 20 minutes postdose/pre-exercise , and 5 , 10 , 15 , 30 , and 60 minutes post-exercise . The primary endpoint was the maximum percent decrease in FEV1 from baseline ( postdose/pre-exercise ) . The percentage of protected ( ≤ 20 % decrease in post-exercise FEV1 ) patients was also assessed . Results . Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo ( LS mean ± SE ; −4.8 % ± 2.8 % versus −22.5 % ± 2.8 % , respectively ) . For levalbuterol , 14/15 ( 93.3 % ) patients had < 20 % decrease in post-exercise FEV1 compared with 8/15 ( 53.3 % ) for placebo ( p = 0.0143 ) . Treatment was well tolerated . Conclusion . Levalbuterol HFA MDI ( 90 μg ) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated . Clinical Implication s. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB In healthy subjects changes in airway calibre during exercise are conflicting and smaller than in asthmatics . Method ological differences could explain the discrepancies between the results obtained in healthy subjects . Therefore , our aim was to assess during exercise the changes in airway diameter and the effects of 200 microg salbutamol ( SAL ) or 40 microg ipratropium bromide ( IPR ) inhalations versus placebo ( PLA ) , using spirometry and respiratory resistance ( Rrs ) . Eight non-asthmatic subjects exercised 9 min at 70 % of their maximal aerobic power after inhalation of 200 microg SAL , 40 microg IPR , or PLA .  Maximal flow-volume curves were obtained before and after inhalations , at 3 ( E3 ) and 6 ( E6 ) minutes of exercise , and during recovery . Rrs were measured by impulse oscillometry before and after inhalation , and immediately at the end of exercise . At rest , FEV ( 1 ) increased significantly after inhalation of SAL and IPR . Rrs decreased only after SAL . During exercise FEV ( 1 ) increased significantly from rest with SAL and IPR while forced mid expiratory flow ( FEF ( 25 - 75 ) ) increased significantly for all conditions . At E6 the rise of FEV ( 1 ) and FEF ( 25 - 75 ) were greater with SAL compared to PLA and IPR . In all conditions Rrs increased significantly immediately at the end of exercise as compared to rest but less than during flow-matched hyperpnea . It is concluded that a similar bronchodilation was observed during exercise with and without anticholinergic drug which suggests a withdrawal of parasympathetic control of airways during exercise in healthy subjects . Nevertheless , the bronchodilation observed during exercise is not maximal since it can be reinforced by beta (2)-mimetic drug The effect of adding ipratropium bromide to treatment with beta-2-adrenoceptor agonists was studied in 13 asthmatic children in a double-blind cross-over trial . In the acute phase of the study inhalation of salbutamol 0.1 mg/kg followed by inhalation of 0.25 mg of ipratropium bromide was found to improve pulmonary function variables to a significantly greater extent than salbutamol followed by placebo . The combined therapy also provided significantly better protection than salbutamol plus placebo against exercise-induced asthma . Maintenance treatment with ipratropium bromide ( two inhalations four times daily , 20 micrograms per inhalation ) in combination with oral terbutaline and aerosolized salbutamol did not alleviate asthmatic symptoms or pulmonary function variables to a degree beyond that achieved with the beta-stimulants alone . There were no side effects associated with the ipratropium bromide treatment . These data suggest that higher doses of ipratropium bromide than are presently used should be tested for maintenance treatment of chronic asthma BACKGROUND Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma , limiting everyday activities important for their physical and social development . OBJECTIVE The purpose of this r and omized , double-blind , placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment , recommended in childhood asthma , to protect patients from exercise-induced bronchoconstriction . METHODS Children 6 to 18 years of age with atopic asthma were r and omized to a 4-week , placebo-controlled , double-blind trial . Patients were r and omly allocated to receive daily 200 microg budesonide ( twice daily , 100 microg per dose ) + 9 microg formoterol ( twice daily , 4.5 microg per dose ; n = 20 ) ; 200 microg budesonide + 5 or 10 mg montelukast ( once daily at bedtime ; n = 20 ) ; 5 or 10 mg montelukast ( n = 20 ) ; 200 microg budesonide ( n = 20 ) ; or placebo ( n = 20 ) . A st and ardized treadmill exercise challenge was performed before and after treatment . RESULTS Exercise-induced bronchoconstriction , reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise , was significantly diminished after 4 weeks in all active treatment groups , and compared with placebo . Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options . CONCLUSION These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma . Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment Since the optimal dose of salmeterol in asthmatic children has not yet been clearly defined , we compared the efficacy and duration of the protective effect of two doses of salmeterol ( 25 and 50 micrograms ) against exercise-induced bronchoconstriction . Twelve children ( aged 7 - 14 yrs ) with asthma were studied in a double-blind , cross-over , placebo-controlled design . On three separate days , exercise tests were performed 1 h and 12 h after administration of the drug . Pulmonary function measurements were performed before drug inhalation , before every exercise test and 1 , 5 , 10 , 15 and 30 min after the end of exercise . The response was expressed as maximal decrease in forced expiratory volume in one second ( FEV1 ) . Both doses of salmeterol provided significant bronchodilation for up to 12 h , with no difference between them . Maximal exercise-induced decrease in FEV1 ( % fall ) 1 h after pretreatment was ( mean + /- SD ) 35 + /- 16 , 10 + /- 10 and 4 + /- 3 % for placebo , 25 and 50 micrograms salmeterol , respectively . At 12 h after pretreatment these values were 31 + /- 14 , 19 + /- 12 and 15 + /- 13 % , respectively . Individual protection against exercise-induced bronchoconstriction at 1 and 12 h did not vary between the dosages ( p < 0.05 ) , even though the protection obtained by 25 micrograms at 12 h was no longer significant versus placebo . We conclude that 25 micrograms of inhaled salmeterol provides equally effective long-lasting bronchodilation and acute protection against exercise-induced bronchoconstriction as 50 micrograms , and may be a suitable dose for most asthmatic children The short-term protective effect on exercise-induced asthma ( EIA ) and the duration of action of formoterol , given by metered dose aerosol at a dose of 24 micrograms , were compared with salbutamol ( 200 micrograms ) and placebo in twelve asthmatic EIA-positive patients in a double-blind , placebo-controlled , three period cross-over study . On each treatment day the patients were given one of the drugs or placebo and two exercise tests were performed at the second and at the eighth hour after dosing . Using a st and ard procedure , exercise was performed by treadmill in well-controlled environmental conditions . In the first test at 2 h a significant difference relative to placebo ( p less than 0.001 ) at each incremental time after exercise ( i.e. 5 , 10 , 15 , 20 , 30 min ) was obtained with both formoterol and salbutamol , without any significant difference between formoterol and salbutamol . After the eighth hour test formoterol still protected against EIA in comparison to both salbutamol and placebo . The effect of salbutamol at this time was not different from placebo .  No adverse effects were reported in any treatment group . Formoterol has a long duration of action in protecting against EIA that persisted for eight hours , removing the need to dose with beta 2-agonist before every exercise The onset of bronchoprotection as obtained by various β2-agonists has not been examined in a comparitive study . In this study , the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting β2-agonists formoterol and salmeterol and the short-acting β2-agonist terbutaline were measured . Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction ( mean baseline forced expiratory volume in one second ( FEV1 ) : 90 % predicted ; mean fall in FEV1 after exercise : 31 % from baseline ) were enrolled in this double-blind , double-dummy , placebo-controlled , r and omized , four-period crossover study . Exercise challenges were performed on 12 days at either 5 , 30 , or 60 min after inhalation of a single dose of formoterol ( 12 µg Turbuhaler ® ) , salmeterol ( 50 µg Diskus ® ) , terbutaline ( 500 µg Turbuhaler ® ) or placebo . Exercise-induced bronchoconstriction ( maximum fall in FEV1 or area under the curve ) did not differ significantly between terbutaline , formorerol and salmeterol either 5 , 30 , or 60 min after inhalation of the study medication . In contrast , the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol ( p<0.05 , each ) , which both showed a similar time course . At all time points between 5 and 60 min , formoterol provided significantly greater bronchodilation than salmeterol ( p<0.05 ) . These data indicate that equipotent doses of the bronchodilators salmeterol , formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction , despite the fact that the time course of bronchodilation was significantly different between the three β2-agonists BACKGROUND Montelukast , a leukotriene receptor antagonist , and salmeterol , a long-acting beta(2)-receptor agonist , each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction ( EIB ) in short-term studies . Direct comparisons between these agents in long-term studies are limited . OBJECTIVE We sought to compare montelukast and salmeterol in the long-term treatment of EIB . METHODS One hundred ninety-seven patients with mild asthma and a postexercise fall in FEV(1 ) of at least 18 % were r and omized ( double-blind ) to receive montelukast 10 mg once daily or salmeterol 50 microg twice daily for 8 weeks . Exercise challenge was repeated at day 3 , week 4 , and week 8 after r and omization near the end of the dosing interval for both drugs . The primary efficacy endpoint was the maximal percent fall in postexercise FEV(1 ) at week 8 . RESULTS Montelukast was effective in treating EIB without inducing tolerance and provided superior ( P < /=.001 ) protection than salmeterol at weeks 4 and 8 , with comparable protection at day 3 . The frequency of respiratory clinical adverse events ( P = .046 ) and discontinuations because of clinical adverse events ( P = .052 ) were less with montelukast . CONCLUSION The effect of montelukast was greater than that of salmeterol in the chronic treatment of EIB over a period of 8 weeks in patients with mild asthma as demonstrated by effect size , maintenance of effect , and fewer respiratory clinical adverse events during the study period . Montelukast may be a better alternative to salmeterol as a controller agent for the chronic treatment of EIB The effect of clenbuterol ( NAB 365 ) in inhibiting  exercise-induced asthma  was compared with that of salbutamol in a single-blind , placebo-controlled , crossover study . Single doses of 20 microgram clenbuterol and 200 microgram salbutamol were given by inhalation 180 minutes before exercise to 9 patients . The exercise used was treadmill running . Clenbuterol offered complete protection to 7 patients , partial protection to 1 and no protection to 1 patient . Salbutamol offered complete protection to 5 patients , partial protection to 1 and no protection to 3 patients . One patient was not protected by any treatment . The protective effects of the two beta-adrenergic bronchodilator drugs were similar ( p = 0.42 for FEV1 and p = 0.10 for FEF25 - 75 % ) . Placebo failed to prevent exercised-induced asthma  in any patient . No adverse reactions were manifested or reported by the patients Spirometry before and after a treadmill exercise two hours after oral administration of 2.5 - 5.0 mg of terbutaline or placebo disclosed that terbutaline produced a highly significant protective effect against exercise-induced asthma . In 14 asthmatic youngsters decreases in FEV1 , PEFR or FEF25 - 75 of at least 15 % followed exercise after placebo The purpose of this study was to determine the safety and effectiveness of albuterol aerosol 180 micrograms and albuterol powder 200 micrograms in the prevention of  exercise-induced bronchospasm in children . Forty-six patients aged 4 - 11 years with asthma and exercise-induced bronchospasm were enrolled in this r and omized , double-blind , single-dose , three-way crossover study comparing albuterol aerosol , albuterol powder , and placebo . Exercise challenge was performed at the screening visit for qualifying and baseline determinations of pulmonary function and then 15 min after drug administration at each of three visits . Prevention of exercise-induced bronchospasm was assessed by comparing across all treatment groups the percentage change in FEV1 from pre- to postexercise , the percentage of patients protected by treatment , postexercise minimum FEV1 , and postexercise change in FEV1 . Safety was assessed by observation of clinical adverse events , laboratory tests , physical examination , electrocardiogram and rhythm strips , vital signs , and pulmonary auscultation .  Forty-four patients completed the study .  Mean postexercise FEV1 decreased 6 % from preexercise values when patients were treated with either albuterol formulation ; FEV1 decreased 23 % when patients were treated with placebo .  Exercise-induced bronchospasm was prevented in 95 % of patients when treated with albuterol powder , in 91 % treated with albuterol aerosol , and in 57 % treated with placebo . Patients maintained significantly higher mean minimum FEV1 values after treatment with albuterol powder and albuterol aerosol than when treated with placebo . Treatment with either albuterol formulation produced a significantly smaller decrease in mean FEV1 from pre- to postexercise than treatment with placebo . No drug-related adverse events were reported , and safety assessment s were within normal limits . ( ABSTRACT TRUNCATED AT 250 WORDS Asthmatic athletes ( adults and junior ) have competed successfully at the highest level for many years assisted by pre-event medication with beta 2-agonists . To examine the impact of beta 2-agonists upon submaximal running economy ( oxygen consumption at a given submaximal work load ) , we studied 10 nonasthmatic boys ( age , 10.4 + /- 0.48 years , mean + /- SD ) . They each completed submaximal ( speeds , 7.2 , 8.0 and 8.8 km/hr ) and peak treadmill running protocol s preceded by treatment with beta 2-agonist ( terbutaline , 500 micrograms via nebuhaler ) or placebo in a r and omized , crossover single-blind study . No significant differences were found between running economy and heart rate during the submaximal exercise tests or between peak oxygen consumption ( VO2 ) , peak respiratory exchange ratio , peak heart rate ( HR ) , or total running time during the peak VO2 test . Pretreatment with terbutaline did produce small but nonsignificant increases in aerobic fractional utilization ( percent peak VO2 on drug : 65.9 % , 72.6 % , and 76.7 % vs. placebo : 65.1 % , 70 % , and 75.5 % ) , at the three submaximal work loads . Respiratory exchange ratio ( RER ) values were elevated throughout the submaximal tests ( on drug : 0.94 , 0.93 , and 0.94 vs placebo : 0.91 , 0.92 , and 0.91 , P < 0.05 ) . No significant differences were found between drug and placebo for minute ventilation ( VE ) and ventilatory equivalent for oxygen ( VE/VO2 ) , at both submaximal and peak exercise intensities . ( ABSTRACT TRUNCATED AT 250 WORDS Svenonius E , Arborelius M , Wiberg R , Ståhl E , Svensson M. A comparison of  terbutaline inhaled by Turbuhaler ® and by a chlorofluorocarbon ( CFC ) inhaler in children with exercise‐induced asthma B2-agonists play a first-rate role in the exercise induced asthma ( EIA ) prevention for their capacity to modulate the bronchial tone . We studied the efficacy of a new B-sympathomimetic ( Broxaterol ) in 10 children ( 7 males and 3 females ) with EIA in double blind vs salbutamol .  During two consecutive days a basal treadmill incremental exercise test was made for determining bronchoconstriction rate ( IB ) . Subsequently the test was repeated 30 ' and 150 ' after the drug 's administration . The Broxaterol premedication determined , by comparison with the basal IB value , a mean difference of 11.9 after 30 ' ( p less than 0.05 ) and 10.0 after 150 ' ( p less than 0.01 ) . No significant correlation was found comparing the salbutamol premedication . In conclusion our data confirms the  Broxaterol efficacy in exercise-induced asthma prevention BACKGROUND Formoterol is a highly effective therapeutic agent in the prevention of exercise-induced bronchospasm ( EIB ) . Regular use of beta-adrenergic drugs may result in a reduction in the protective effect afforded by these bronchodilators against bronchoconstrictor stimuli . It is unknown whether this effect extends to formoterol and exercise . METHODS We performed a r and omized , double-blind , parallel clinical trial in 19 patients with EIB . Each patient received inhaled formoterol or placebo twice daily during 4 weeks . Patients performed two exercise tests in a cycle ergometer on the 1st , 14th , and 28th study days separated 3 hours from each other . A dose of formoterol was given 30 min prior to the 2nd test . RESULTS There were significant differences in bronchoprotection between days 1 and 14 ( p = .012 ) and between days 1 and 28 ( p = .012 ) in the formoterol group . No differences were found in the placebo group . The evolution of the bronchoprotection index was also significantly different between the formoterol and the placebo group ( p = .002 ) from day 1 to 28 . CONCLUSIONS Tachyphylaxis developed to the protective effect of formoterol against EIB after 4 weeks of regular dosing . Tolerance was already found on day 14 , though not progressive . Formoterol should be recommended only as needed in EIB This double-blind crossover study compared the therapeutic value of bronchodilator procaterol hydrochloride at 5 micrograms per puff by aerosol inhalation using a metered-dose inhaler and at 25 micrograms by oral administration using tablets with respective inert placebos in preventing exercise-induced bronchospasm ( EIB ) in 10 children with bronchial asthma . The two active dosage formulations produced a significant EIB inhibitory effect compared with the placebos . In a comparison of the two active preparations , the aerosol was more efficacious than the tablet in improving all respiratory parameters examined , and statistical significance was obtained in FEV1 , MMEF , PEFR , V50 , and V25 5 minutes after exercise . Further , the aerosol was beneficial in all subjects , while the tablet was beneficial in seven of 10 INTRODUCTION Montelukast has been proven to assure a protective effect against exercise-induced bronchoconstriction . AIM To verify exactly when montelukast begins protection in asthmatic children by evaluating different time intervals between dosing and challenge . METHODS In a double blind , placebo-controlled , three day doses , crossover study , patients were r and omized to receive in sequence treatment with either a placebo or montelukast and assigned to one of seven groups that were tested 1 , 2 , 3 , 4 , 5 , 6 and 8 h after drug administration , respectively . For each group , the exercise challenge was always performed at the same hour on the first and third days of treatment . RESULTS Sixty-nine asthmatic children took part in the study . On day 3 , the mean FEV(1 ) % fall from baseline was 25.54 ( 95 % CI = 21.63/29.46 ) and 14.89 ( 95 % CI = 11.85/17.92 ) for the placebo and active drug ( p < 0.05 ) , respectively . On day 1 , the mean fall of FEV(1 ) was 28.20 ( 95 % CI = 24.46/31.94 ) and 19.01 ( 95 % CI = 15.71/22.31 ) for the placebo and montelukast ( p < 0.05 ) , respectively . Clinical protection was achieved in 21 ( 30 % ) and 33 ( 48 % ) subjects by montelukast on the first and third days , respectively . CONCLUSIONS Montelukast assured protection against exercise-induced bronchoconstriction from the first through the eighth hour from the first day of treatment . However , individual susceptibility to protection was evident since some individuals were not protected at any time . We conclude that in clinical use individual responses to the drug should be carefully evaluated in the follow-up management PURPOSE As new delivery devices and formulations are being introduced for drugs given by inhalation , there is a need to evaluate their equivalence with old preparations . One way to do this is to investigate their equivalence in protecting from exercise-induced asthma ( EIA ) . METHODS We used a protocol for EIA to compare the protective effect of salbutamol delivered by the pressurised metered dose inhaler ( pMDI ) and the new Diskus dry powder device .  Twenty-seven asthmatic subjects with moderately severe EIA completed an exercise test on four separate days at two study centers . Exercise was performed by cycling for 8 min while inhaling dry air ( 0 % RH , 20 - 24 degrees C ) . The target workload in W was predicted as ( 53.76 x predicted FEV1 ) - 11.07 and 95 % of this target was achieved at 4 min of exercise . This target was chosen in order to achieve ventilation between 50 and 60 % of predicted maximum in the last 4 min . RESULTS There was no significant difference in the workload , ventilation , or heart rate achieved on the study days . The severity of EIA was measured as the % fall in FEV1 . EIA severity was similar on the placebo and control day and the coefficient of variation was 19.4 % . The mean + /- SD % fall on the control , placebo , salbutamol by Diskus , and pMDI were 42.0 % + /- 15 , 39.4 % + /-17.6 , 13.4 % + /- 13.2 , and 8.5 % + /- 13.8 , respectively . Salbutamol significantly inhibited the % fall in FEV1 after exercise , and there was no difference between the preparations . CONCLUSION The protocol described here is suitable for evaluating equivalence of salbutamol preparations in protecting against EIA and could be used to evaluate the protective effect of other medications Physical exercise is a common trigger for bronchial asthma . We evaluated the preventive effect on exercise-induced bronchospasm ( EIB ) of a single 42 micrograms dose of salmeterol , a uniquely long-acting inhaled bronchodilator , and compared salmeterol with 180 micrograms albuterol in two independent , r and omized , double-blind ,  placebo-controlled studies involving 161 subjects . Three exercise challenges were conducted over 12 h , and bronchoconstriction following the serial challenges was assessed as change in FEV1 compared with predose values . The mean maximal percentage decrease in FEV1 after the three exercise challenges was 5 % at 0.5 h , 8 % at 5.5 h , and 13 % at 11.5 h postdose in the salmeterol group compared with 7 , 25 , and 27 % , respectively , in the albuterol group and 27 , 27 , and 26 % , respectively , in the placebo group ( p < 0.001 , overall treatment difference ) . Albuterol provided complete protection against EIB ( defined as < 10 % decrease in FEV1 compared with predose values ) only after the first exercise challenge , but salmeterol continued to provide complete protection in the majority of subjects after each exercise challenge : 80 % ( 44 of 55 ) at 0.5 h , 70 % ( 37 of 53 ) at 5.5 h , and 55 % ( 29 of 53 ) at 11.5 h. Electrocardiographic monitoring revealed no clinical ly significant changes in any treatment group 15 and 30 min following each exercise challenge . In summary , these data demonstrate that salmeterol is effective against EIB and that a single 42 micrograms dose can prevent EIB for up to 12 Eighteen adult asthmatics participated in a placebo controlled , double-blind , r and omised study comparing the efficacy of pretreatment with fenoterol administered by pressurized aerosol and as a dry powder on exercise-induced asthma .  The dosages used were 0.6 mg and 1.0 mg as both pressurized aerosol and dry powder . The pretreatment was given over a period of 10 min . Six min of treadmill-running was performed in a climate chamber 30 min after pretreatment on five successive days . The lung function was assessed by peak expiratory rate . The decrease in lung function following pretreatment with placebo was 32 % ( average + /- ( SEM ) ( 2 ) . Falls of 9 % ( 2 ) and 8 % ( 1 ) were seen after pretreatment with 0.6 and 1.0 mg from a pressurized aerosol . The falls following pretreatment with 0.6 and 1.0 mg of dry powder were 8 % ( 2 ) and 8 % , respectively . It is concluded that pretreatment of exercise-induced asthma with a beta-2-agonist is equally effective whether dosed from a pressurized aerosol as when given as a dry powder . A dose of 0.6 mg is just as effective as a dose of 1.0 mg when inhaled over a period of ten min 1 Healthy volunteers undertook submaximal grade d exercise while objective measurements of cardio-respiratory function were made and breathlessness was assessed with serial visual analogue scales . 2 A useful and consistent relationship existed between breathlessness and ventilation for individual subjects . 3 Drugs were examined in this system to test whether they modified the relationship between ventilation and breathlessness such that less breathlessness occurred for a given level of ventilation . 4 Salbutamol , ipratropium bromide and disodium cromoglycate given by inhalation did not reduce breathlessness in healthy subjects during exercise Bricanyl ® Turbuhaler ® ( 0.5 mg terbutaline sulphate ) and Ventolin ® Rotahaler ® ( 0.4 mg salbutamol ) were compared in a r and omized double‐blind placebo controlled study on exercise‐induced asthma in 19 children ( 14 boys ) aged 7‐14 years . The study was carried out on 3 separate days . Asthmatic attacks were provoked by free range running . Peak expiratory flow ( PEF ) was measured before and after exercise . If PEF decreased by > 20 % , one inhalation from each of the inhalers was given under supervision of the investigator . Only one of the inhalers ( none on the placebo day ) delivered active drug . PEF was measured again 5 and 10 min after treatment . Already 5 min after treatment PEF had returned to baseline after active treatment . There was no statistically significant difference between the two active treatments . After placebo treatment , PEF did not return to baseline even at the 10 min post‐exercise measurement . Ten children needed extra medication after the last PEF measurement on the placebo day , whereas no child needed extra medication after any of the active treatments . No adverse events were reported in this study . In conclusion , Bricanyl Turbuhaler ( 0.5 mg ) and Ventolin Rotahaler ( 0.4 mg ) were equally efficacious in the treatment of exercise‐induced asthma in children Exercise-induced bronchoconstriction is common in patients with chronic asthma ( 1 ) . Airway cooling or desiccation during exercise may trigger activation of mast cells and release of such mediators as histamine and cysteinyl leukotrienes , result ing in bronchospasm ( 1 , 2 ) . Cysteinyl leukotrienes ( LTC4 , LTD4 , and LTE4 ) , synthesized from arachidonic acid through the 5-lipoxygenase pathway , are potent bronchoconstrictors , with an effect greater than 1000 times that of histamine ( 3 - 5 ) . Several research ers have demonstrated an increase in urinary concentrations of LTE4 after exercise ( 6 , 7 ) . Prophylaxis against exercise-induced bronchoconstriction with inhaled mast cell-stabilizing agents and short-acting -agonists must be administered 15 to 30 minutes before exercise . The long-acting inhaled -agonist salmeterol protects against exercise-induced bronchoconstriction for up to 12 hours , thus providing more flexibility in the dosing schedule for active patients with asthma ( 8 , 9 ) . However , in some patients , tolerance to salmeterol develops with long-term use , and the level of bronchoprotection diminishes by 6 to 9 hours ( 10 - 12 ) . Montelukast sodium , a leukotriene receptor antagonist , is a potent oral medication for the treatment of asthma . The leukotriene receptor antagonists have demonstrated a significant bronchoprotective effect with exercise after one or two doses ( 13 , 14 ) . In patients with exercise-induced bronchoconstriction , short-term treatment with montelukast ( Singulair , Merck & Co. , Inc. , Whitehouse Station , New Jersey ) given once daily diminished the postexercise response , as described by the area under the FEV1 time curve ( AUC0 - 60 min ) , by more than 50 % , even at the end of the dosing interval ( 20 to 24 hours after administration ) ( 15 , 16 ) . Furthermore , tolerance to the bronchoprotective effects of montelukast did not occur with long-term administration ( 17 ) . We sought to test the hypothesis that the bronchoprotective effects of montelukast were greater than those of salmeterol in patients with chronic asthma who experienced exercise-induced bronchoconstriction . Methods Design We conducted a r and omized , parallel-group study consisting of a 2-week , single-blind placebo baseline period followed by an 8-week , double-blind treatment period with montelukast sodium ( 10-mg tablet taken orally once in the evening ) or inhaled salmeterol ( 50-g aerosol formulation [ 2 puffs ] taken twice daily ) . Seventeen clinical study sites participated in the trial . To mask formulation differences , a double-dummy treatment regimen was used . Each patient received one tablet daily ( active agent or matching placebo ) or one inhaler twice daily ( active agent or matching placebo ) for both the single-blind and double-blind treatment periods . A computer-generated allocation schedule with a blocking factor of 4 was produced by the statistician . Each center was given a block of allocation numbers that were assigned sequentially to consecutive r and omly assigned patients . Spirometric measurements were obtained before and after st and ardized exercise challenges at the beginning and end of the baseline period , within the first 3 days of the double-blind treatment period , and at weeks 4 and 8 of the treatment period . Additional measurements were physical examination , vital signs , electrocardiography , chest radiography , and laboratory tests ( hematology , chemistry profile , and urinalysis ) . At each visit , all spontaneously reported adverse events were recorded . The protocol was approved by the institutional review board of each site , and written informed consent was obtained from each patient . Inclusion Criteria Male and female patients 15 to 45 years of age with a history of chronic asthma were enrolled . All patients had an FEV1 of at least 65 % of the predicted value at rest and a decrease in FEV1 of at least 20 % after a st and ardized exercise challenge on two occasions during the baseline period . All patients had been nonsmokers for at least 1 year and had a smoking history of less than 15 pack-years . Exclusion Criteria Persons who had upper respiratory infection or exacerbation of asthma requiring emergency care within the past month or were hospitalized for asthma in the past 3 months were excluded . Use of oral or inhaled corticosteroids , theophylline , cromolyn sodium , nedocromil , oral -agonist , and long-acting antihistamines was prohibited before and during the study . Use of inhaled albuterol for symptomatic relief of asthma and use of short-acting antihistamines were permitted . Evaluations A st and ard spirometer ( Puritan-Bennett PB100/PB110 , Puritan-Bennett , Wilmington , Massachusetts ) was used to obtain all spirometric measurements according to American Thoracic Society st and ard criteria ( 18 ) . Patients had to have discontinued use of inhaled short-acting -agonists for 6 hours before the visit . Exercise testing was done in the early afternoon near the trough of effect for both drugs according to a method described elsewhere ( 17 ) . Measurements were obtained 20 and 5 minutes before exercise ( prechallenge period ) . Exercise challenge was performed only if the average FEV1 in the prechallenge period was greater than 65 % of predicted ; otherwise , the test was rescheduled . Patients  exercised on a treadmill while inhaling room temperature , compressed , dry air . During the first test , the speed and gradient of the treadmill were adjusted to achieve 80 % to 90 % of the patient 's age-predicted maximum heart rate . The setting s were maintained for a total of 6 minutes ; the same setting s were used for future tests . This level of exercise has been used to quantify the level of bronchoconstriction associated with regular exercise ( 19 ) . Serial spirometric measurements were obtained at 0 , 5 , 10 , 15 , 30 , 45 , and 60 minutes after exercise ( postexercise period ) . Additional measurements were carried out at 15-minute intervals for up to 90 minutes if the patient 's FEV1 had not returned to within 5 % of the prechallenge value by 60 minutes . If the patient 's FEV1 did not return to the prechallenge value by 90 minutes after exercise , a rescue dose of inhaled -agonist was administered at the discretion of the study investigator . Statistical Analysis An all- patients -treated analysis , which included patients with a baseline visit and at least one post-r and omization visit , was performed . The change from baseline in the maximal percentage decrease in FEV1 after exercise at the end of 8 weeks of treatment was the primary end point . Analysis of variance was used to compare the two treatment groups . The analysis of variance model included terms for treatment , center , and the interaction of treatment and center . Ninety-five percent CIs for within-group means and the difference between groups were constructed to assess the magnitude of the treatment effect . Analysis of variance on the ranked data was used to analyze percentage inhibition for all end points . In the event of early termination of the exercise challenge because of administration of rescue medication , the largest percentage decrease in FEV1 achieved before administration of rescue medication was used in the analysis . Secondary end points were change from baseline for maximal percentage decrease in FEV1 at days 1 to 3 and week 4 , the time required after maximal decrease in FEV1 to return within 5 % of prechallenge values ( time to recovery ) , and the AUC0 - 60 min at all visits . The mean of the 20- and 5-minute prechallenge measurements was used as the pre-exercise FEV1 value . If a patient required rescue with inhaled -agonist during the postexercise period , the last recorded FEV1 value was used and carried forward for all subsequent readings and 100 minutes was entered for the end point of time to recovery . The AUC0 - 60 min was calculated by using the trapezoidal method . If a patient 's FEV1 did not decrease below 95 % of the prechallenge value , the time to recovery was assigned a value of zero . The persistence of effect over time was assessed by using a repeated- measures fixed-effects model with terms for center , treatment group , time , and the interaction of treatment group and time to calculate the rate of change over the treatment period . Persistence of effect was defined as a slope of zero . The magnitude of the slopes for each treatment group was estimated , and 95 % CIs were calculated . An overall test of equal slopes between the treatment groups was examined , and a 95 % CI on the difference in slopes between treatment groups was provided . The number and percentage of patients requiring rescue medication  during or at the end of the exercise test were summarized by treatment group at each time point . In addition , the number and percentage of patients whose decrease in FEV1 from pre-exercise levels was less than 10 % , 10 % to 20 % , 20 % to 40 % , and greater than 40 % were summarized by treatment group for each visit . The overall incidence of adverse events and laboratory abnormalities was assessed by using the Fisher exact test , and within-group changes in the number of laboratory abnormalities were assessed by using the McNemar test . Descriptive statistics were provided by treatment group for patient demographic characteristics , clinical characteristics , and baseline profile . The study was design ed with a sample size of 160 patients ( 80 patients per treatment group ) to have 95 % power ( two-sided test at = 0.05 ) to detect a 7 % difference in the mean change in maximal percentage decrease in FEV1 between treatments . All statistical analyses were performed by using SAS software , version 6 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source Funding for this trial was provided by Merck & Co. , Inc. , Whitehouse Station , New Jersey . Personnel from Merck U.S. Human Health , Clinical Development department played a significant role in the design , conduct , and analysis of the trial . The trial was conducted in accordance with guidelines for clinical trials of investigational agents established by U.S. regulatory authorities . Results OBJECTIVE Physical activity is an important and frequent trigger of airways obstruction in asthmatic children . We aim ed to compare the efficacies of 50 microg salmeterol twice daily and 2 mg SCG four times daily with respect to protection from exercise induced bronchoconstriction ( EIB ) . METHODS Twenty seven children and adolescents aged 4 to 16 years with mild or moderate exercise induced asthma ( FEV1 70 % to 90 % predicted ) were admitted to the study .  Exercise challenge was performed on a treadmill using a predefined protocol in order to produce 10 minutes of exercise at near-maximum targets . The trial had a r and omised , cross-over design comprising a 3-day run-in period and two 7-day treatment periods , separated by a one-week washout period . RESULTS The mean protective efficacy of salmeterol was larger than that of SCG . A difference between treatments of 39.7 % ( 95 % CI , - 0,8 to 68.9 % ) in favour of salmeterol was calculated using a Hodges-Lehmann-estimate . The maximum post-challenge fall in FEV subset 1 was significantly lower ( p<0.001 ) after salmeterol than after SCG ( - 5.6 + /- 6.4 % vs. -12.1 + /- 9.3 % , respectively ) . In addition , salmeterol improved base-line lung function to a greater degree than SCG . FEV1 increased by 0.4 l/sec after salmeterol , whereas no improvement was observed after SCG . CONCLUSIONS A one-week treatment with salmeterol 50 microg b.i.d in asthmatic children and adolescents provided better protection against EIB and improved baseline lung function as compared to SCG four times daily Oxitropium bromide ( Ba 253 ) is a new inhaled bronchodilating agent with anticholinergic properties . The effect of this compound ( 100 micrograms ) was compared to that of ipratropium bromide ( 40 micrograms ) , the beta 2-receptor stimulant fenoterol ( 400 micrograms ) and placebo in 8 patients with exercise-induced asthma . The drugs were administered by metered dose inhalers , after which exercise test were performed on ergometer cycles at the times of the drugs ' maximal effects . Forced expiratory volume during 1 S and vital capacity were recorded basally , repeatedly during 20 min after exercise and following the inhalation of isoprenaline ( 160 micrograms ) which was given 20 min after exercise . Fenoterol possessed a very good protective effect against exercise-induced bronchoconstriction in all patients , whereas the other drugs differed very little from placebo . Thus , only 4 patients did benefit from ipratropium bromide , 1 patient from oxitropium bromide and 2 patients from placebo .  No side effect occurred . In the doses used the two anticholinergic agents ipratropium bromide and oxitropium bromide were less effective than a beta 2-adrenoreceptor stimulant like fenoterol in protecting against exercise-induced asthma Procaterol and albuterol , beta agonists , were studied using a placebo-controlled , repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma ( EIA ) .  Fifty-three subjects aged 12 to 50 years who had at least a 20 % drop in FEV1 during a screening exercise tolerance test were entered . Subjects took two inhalations of procaterol ( 10 micrograms/inhalation ) , albuterol ( 90 micrograms/inhalation ) , or placebo . Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80 % aerobic O2 consumption for six minutes . Pulmonary function was measured before and serially for 30 minutes after exercise . The same exercise challenge was repeated three , six , and nine hours after drug administration . Both procaterol and albuterol  bronchodilated and modified EIA at 30 minutes and three hours , mean drops in FEV1 being 8.2 and 9.7 % respectively at 30 minutes and 16.8 and 16.3 % at three hours . This was compared with placebo falls of 30 % and 26 % . At six hours the subjects ' response was similar after both procaterol and albuterol , and fewer subjects had a 20 % fall in FEV1 than with placebo , although protection afforded by both beta agonists was substantially less than at three hours . Both drugs were tolerated well The aim of the present study was to compare the effect of Bricanyl Turbuhaler ( 0.5 mg x 1 terbutaline ) with the effect of albuterol metered dose inhaler ( 0.1 mg x 2 albuterol ) in patients with reproducible bronchoconstriction . The study was performed as a double-blind placebo-controlled trial in sixteen asthmatic adults . Bronchoconstriction was induced by steady state running on a treadmill . Both 0.5 mg terbutaline and 0.2 mg albuterol have good bronchodilating effects in patients with exercise-induced asthma . There was , however , a faster onset of action after albuterol . The clinical value of this observed difference is uncertain BACKGROUND With long-term administration of salmeterol , the extent of protection afforded by the drug against experimental precipitants of asthma such as methacholine and adenosine may decrease . Whether this effect extends to a clinical ly relevant stimulus such as exercise is unknown . METHODS We performed a r and om-order , double-blind , crossover trial in 20 patients with exercise-induced asthma . Each patient received inhaled salmeterol or placebo twice daily for a month , with a one-week washout period between treatments . The patients performed cycle ergometry while breathing frigid air 30 minutes after the morning dose and 9 hours later on the 1st , 14th , and 29th study days . The primary end point was the extent of the decrease in forced expiratory volume in 1 second ( FEV1 ) 10 minutes after exertion . RESULTS With placebo , significant airway narrowing developed at all times ( mean [ + /-SE ] decrease from base line in FEV1 , 19+/-2 percent in the morning and 18+/-2 percent in the evening ) . The morning dose of salmeterol attenuated the degree of bronchoconstriction at all times ( decrease in FEV1 on day 1 , 5+/-2 percent ; on day 14 , 10+/-3 percent ; and on day 29 , 9+/-3 percent ; P=0.10 ) . Its ability to act throughout the day , however , decreased with long-term administration ( decrease in FEV1 from morning to evening on day 1 , 6+/-2 percent ; on day 14 , 15+/-3 percent ; and on day 29 , 14+/-3 percent ; P=0.003 ) . CONCLUSIONS Protection against exercise-induced asthma is maintained with long-term administration of salmeterol , but the length of time that the drug remains active after a single dose decreases The aim of this study was to investigate whether the long-acting beta-agonist salmeterol affects athletic performance in patients with asthma . The effect of 50 micrograms salmeterol on the cardiorespiratory responses to a progressive maximal cycle exercise test and on endurance capacity ( defined as the exercise duration at 70 % maximum oxygen uptake ) , was compared with 200 micrograms salbutamol and a matched placebo in eight asthmatic men . Both salmeterol and salbutamol improved pre- and postexercise forced expiratory volume in one second ( FEV1 ) for maximal and endurance exercise . Following active treatment , patients exercised from a significantly high baseline FEV1 , with both salmeterol ( 3.58(1.16)l ) ( mean ( SD ) ) and salbutamol ( 3.55(1.24)l ) compared with placebo ( 3.29(1.35)l ) . Similar improvements preceded endurance exercise . Cardiorespiratory , haemodynamic or subjective responses to the progressive maximum exercise tests were not different with salmeterol , salbutamol or placebo , nor did endurance capacity change with any treatment modality . Blood lactate levels , after 15 min exercise , were significantly higher with salbutamol ( 3.64 ( 1.83 ) mM ) , but not with salmeterol ( 3.03 ( 1.64 ) mM ) , compared with placebo ( 2.95 ( 1.69 ) mM ) . These results demonstrate the absence of significant cardiorespiratory or metabolic effects during exercise after a single dose of salmeterol , together with a lack-of ergogenic effect , as measured by maximal or endurance exercise performance , in patients with asthma We compared the inhibitory effects of inhaled salbutamol ( S ) , ipratropium ( I ) , and cromoglycate ( C ) on bronchospasm induced by exercise ( EX ) or hyperosmolar ( HY ) saline aerosol in a group of 11 subjects with stable asthma . Each subject had eight tests in a r and omized order , four EX and four HY challenges , each preceded by the double-blind inhalation of either a placebo , 200 micrograms of S , 80 micrograms of I , or 4 mg of C. This study demonstrated that the three drugs protected against the two types of challenges in almost all subjects . Although we observed a large interindividual variability in the airway response to the challenges , there was no statistically significant difference in the mean percent protection after HY or EX challenges when these challenges were preceded by S , I , or C ( p greater than 0.05 ) . Moreover , for EX- and HY-induced bronchospasm , the mean percent protection afforded by the three medications was in the same order ( S greater than I greater than C ) , although the protective effect against EX-induced was weaker than against HY-induced bronchospasm . This suggests that hyperosmolarity , although it may not be the sole factor involved , plays a role in EX-induced bronchospasm Background . A powder formulation of salmeterol has been shown to prevent exercise-induced bronchospasm ( EIB ) in asthmatic children and adults ; however , the delivery device ( Diskhaler ; Glaxo Wellcome Inc , Research Triangle Park , NC ) must be reloaded after 4 doses . A new multidose powder inhaler ( Diskus ) provides 60 doses of salmeterol in a blister pack presentation with a dose counter . Objective . To evaluate the safety and efficacy of 50-μg salmeterol powder via two different delivery systems ( Diskhaler and Diskus ) in preventing EIB in asthmatic children . Study Design . A r and omized , double-blind , double-dummy , single-dose , placebo-controlled , three-way crossover study was conducted in 24 children 4 to 11 years of age demonstrating EIB and mild to moderate asthma . Serial forced expiratory volume in 1 second ( FEV1 ) was measured before and after treadmill exercise challenges conducted at 1 , 6 , and 12 hours after study drug administration . Adverse events were also assessed . Results . During all exercise challenges , EIB-mediated reductions in FEV1 were minimized or prevented in patients receiving single doses of salmeterol powder compared with placebo . Single doses of salmeterol powder delivered via either system were equally effective in preventing EIB . There were no drug-related adverse events , cardiovascular , or other clinical ly relevant safety concerns . Conclusions . Single doses of salmeterol powder delivered by either delivery system are safe and effective in preventing EIB for ≥12 hours in asthmatic children BACKGROUND Secondary to the phase-out of chlorofluorocarbons ( CFCs ) , the albuterol ( Ventolin , GlaxoSmithKline , Uxbridge , Middlesex , United Kingdom ) pressurized metered-dose inhaler ( MDI ) has been formulated in a non-ozone-depleting propellant , hydrofluoroalkane ( HFA ) 134a . OBJECTIVE To compare the efficacy of albuterol HFA to albuterol CFC and placebo HFA in protecting patients from exercise-induced bronchospasm ( EIB ) . METHODS R and omized , double-blind , placebo-controlled , three-way crossover study in patients with documented EIB . Patients ( n = 24 ) aged 18 to 45 years old received albuterol HFA or albuterol CFC , ( total dose of 180 microg ex-actuator ) , or placebo HFA via an MDI , 30 minutes before a st and ardized exercise challenge . Serial forced expiratory volume in 1 second ( FEV1 ) measurements were made 5 minutes before exercise and 5 , 10 , 15 , 20 , 25 , 30 , and 60 minutes postexercise . The primary outcome measure was the maximum percentage fall in FEV1 over the 60 minutes after exercise . RESULTS The adjusted mean maximum percentage falls in FEV1 postexercise for albuterol HFA and CFC groups were 15.4 % and 14.9 % , respectively . The two formulations were comparable with a treatment difference of -0.5 % ( P = 0.848 ; 95 % confidence interval , -5.3 to 4.4 % ) . When compared with the fall in FEV1 for placebo ( 33.7 % ) , both active treatments demonstrated a significantly smaller fall in FEV1 postexercise ( P < 0.001 ) . Safety profiles were similar among the three treatment groups . CONCLUSIONS The results provide assurance to prescribers that the formulation of albuterol in the non-ozone-depleting propellant HFA 134a has not affected its efficacy in the treatment of EIB in asthmatic patients . Single doses of albuterol HFA and CFC from an MDI are comparable in terms of efficacy and safety on a microgram per microgram basis Pretreatment with inhaled beta 2-agonists is often recommended for the prevention of exercise-induced bronchoconstriction . Regular treatment with inhaled beta 2-agonists has been associated with worsened baseline airway caliber and increased airway responsiveness . In this study , we have investigated the effects of regular inhaled albuterol on the severity of exercise-induced bronchoconstriction using a double-blind , placebo-controlled , r and omized , crossover design . Ten subjects inhaled either albuterol or placebo ( 2 x 100 micrograms , four times per day ) for 7 d. On the eighth and ninth days of treatment periods , subjects performed 5-min constant work rate cycle ergometry exercise challenges after inhaling 200 micrograms of placebo ( eighth day ) or albuterol ( ninth day ) . Forced expired volume in 1 s ( FEV1 ) was measured on arrival in the laboratory as well as before and for 1 h after exercise . One week of regular inhaled albuterol compared with placebo result ed in : ( 1 ) a lower baseline FEV1 ( mean difference , 230 ml ) ( p = 0.02 ) ; ( 2 ) a lower minimum postexercises FEV1 without inhaled albuterol pretreatment ( mean difference , 390 ml ; range , -50 ml to 1,250 ml ) ( p = 0.01 ) ; ( 3 ) a lower minimum postexercise FEV1 with inhaled albuterol pretreatment ( p < 0.01 ) . The smallest degree of exercise-induced bronchoconstriction occurred after a week of regular placebo and pretreatment with inhaled albuterol immediately before exercise . Inhalation of albuterol four times daily for 1 wk worsens exercise-induced bronchoconstriction ; however , it remains extremely effective when used immediately before exercise for preventing bronchoconstriction Short-acting inhaled beta2-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction ( EIB )  in children . This was a r and omized , single-blind , placebo-controlled , four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoroalkane-134a ( HFA ) to albuterol formulated in chlorofluorocarbons ( CFCs ) and to placebo in protecting asthmatic children age 6 - 11 from EIB . Patients self-administered either HFA albuterol , two different CFC albuterol products , or placebo 30 min prior to exercise challenge .  Spirometry was performed predose and 5 , 10 , 15 , 30 , 45 , 60 , 75 , and 90 min after the exercise challenge was completed . The smallest percent change from the predose forced expiratory volume in 1 sec ( FEV1 ) after exercise challenge was similar for the three active treatments , and each of the active treatments was significantly better than placebo . Each active treatment had significantly fewer patients unprotected from EIB ( unprotected defined as having > 20 % fall in FEV1 after exercise challenge ) than placebo . Changes in heart rate , blood pressure and electrocardiogram ( ECG ) intervals were similar for the three active treatments following exercise . HFA albuterol is as effective as albuterol products formulated in CFCs and more effective than placebo in protecting asthmatic children from EIB In patients with asthma , exercise-induced symptoms are well recognized and frequently limiting . Currently available beta 2-receptor agonists have a short duration of action and breakthrough symptoms may occur . We studied the efficacy of the recently developed long acting inhaled beta 2-agonist salmeterol with respect to protection against exercise-induced bronchoconstriction .  Twelve patients with mild to moderate , stable asthma were recruited ( age range 21 - 33 years ) . They each underwent treadmill exercise tests , with target heart rate of approximately 90 % of predicted maximum , 1 , 6 and 12 h after a single dose of salmeterol 50 micrograms , salbutamol 200 micrograms and placebo . Patients breathed through a two-way valve , inspiring dry air from a compressed air cylinder via a Douglas bag to maintain constant humidity . The primary efficacy variable analysed was the maximum percentage fall in FEV1 and FVC from pre-exercise readings within the first 30 min post-exercise . At 1 h post-dose there was significant protection in terms of fall in mean + /- SEM FEV1 in response to exercise challenge after either salmeterol ( 0.83 + /- 6.2 % ) or salbutamol ( 3.8 + /- 5.5 % ) as compared with placebo ( 27.1 + /- 7.3 % ) . At 6 h post-dose , fall in FEV1 on salmeterol was 11.3 + /- 3.8 % as compared with salbutamol , 28.0 + /- 5.7 % and placebo , 32.0 + /- 7.0 % . At 12 h post-dosing there was still significant protection in terms of fall in FEV1 in the salmeterol treated group , 12.8 + /- 4.9 % , as compared with salbutamol , 28.7 + /- 4.9 % and placebo , 25.4 + /- 7.3 % . ( ABSTRACT TRUNCATED AT 250 WORDS The main aim of this study was to evaluate the comparative and additive effects of caffeine and albuterol ( short-acting beta (2)-agonist ) on the severity of EIB .  Ten asthmatic subjects with EIB ( exercise-induced bronchoconstriction ) participated in a r and omized , double-blind , double-dummy crossover study . One hour before an exercise challenge , each subject was given 0 , 3 , 6 , or 9 mg/kg of caffeine or placebo mixed in a flavored sugar drink . Fifteen minutes before the exercise bout , an inhaler containing either albuterol ( 180 microg ) or placebo was administered to each subject . Pulmonary function tests were conducted pre- and post-exercise . Caffeine at a dose of 6 and 9 mg/kg significantly reduced ( p<0.05 ) the mean maximum % fall in post-exercise FEV ( 1 ) to -9.0+/-9.2 % and -6.8+/-6.5 % respectively compared to the double-placebo ( -14.3+/-11.1 % ) and baseline ( -18.4+/-7.2 % ) . There was no significant difference ( p>0.05 ) in the post-exercise % fall in FEV ( 1 ) between albuterol ( PLUS CAFFEINE PLACEBO ) ( -4.0+/-5.2 % ) and the 9 mg/kg dose of caffeine ( -6.8+/-6.5 % ) . Interestingly , there was no significant difference ( p>0.05 ) in the post-exercise % fall in FEV ( 1 ) between albuterol ( PLUS CAFFEINE PLACEBO ) ( -4.0+/-5.2 % ) and albuterol with 3 , 6 or 9 mg/kg of caffeine ( -4.4+/-3.8 , -6.8+/-5.6 , -4.4+/-6.0 % respectively ) . Similar changes were observed for the post-exercise % fall in FVC , FEF ( 25 - 75 % ) and PEF . These data indicate that moderate ( 6 mg/kg ) to high doses ( 9 mg/kg ) of caffeine provide a significant protective effect against EIB . It is feasible that the negative effects of daily use of short-acting beta (2)-agonists by asthmatic athletes could be reduced simply by increasing caffeine consumption prior to exercise Albuterol aerosol was compared with isoproterenol and placebo in a double-blind , cross-over study in 12 asthmatic children . A significant increase in mean peak expiratory flow rate 15 minutes after albuterol inhalation persisted for at least five hours after treatment . Inhalation of albuterol one hour before treadmill exercise inhibited exercise-induced bronchospasm Peak expiratory flow ( PEF ) and plasma concentrations of platelet factor 4 and beta thromboglobulin were measured before and after exercise in nine asthmatic patients and 12 non-asthmatic volunteers .  Exercise was preceded by administration in r and om order of either placebo , salbutamol 200 micrograms , or sodium cromoglycate 2 mg from a pressurised inhaler . In control subjects there were minimal changes in PEF and plasma concentrations of platelet factor 4 and beta thromboglobulin . In the asthmatic patients the typical changes in PEF were seen on exercise ; plasma concentrations of platelet factor 4 and beta thromboglobulin rose significantly in parallel , the rise preceding the fall in PEF . The changes in peak flow and platelet activation induced by exercise were attenuated by prior administration of salbutamol or cromoglycate . These results indicate that exercise induced asthma is associated with a rise in platelet release products similar to that observed in antigen induced asthma Treatment for exercise induced asthma ( EIA ) in sporting competition is controlled to prevent the use of agents which might enhance physical performance . There is little information concerning the effects of the long-acting inhaled , and oral , sustained release type bronchodilators on the cardiorespiratory effects of submaximal exercise . The aim of this study was to compare the cardiorespiratory effects of submaximal exercise in patients with EIA before and after pretreatment with high-dose inhaled salmeterol xinafoate ( SX ) and controlled release oral salbutamol ( CR ) .  Patients were treated with SX ( 100 micrograms b.d . ) and CR ( 8 mg b.d . ) for > or = 3 days in a double-blind r and omized cross-over design , with a 5 - 14 day washout period between treatments . A submaximal exercise test ( total exercise time 6 min , final 3 min at 60 % of VEpeak ) was performed prior to each treatment period , and repeated at 1 , 6 , and 12 h postdose at the end of the treatment period . Two subjects were withdrawn from the study . Three subjects required relief medication after 1 h ( CR ) and one subject after 6 h ( SX ) and they did not perform further exercise tests . Both treatments increased baseline FEV1 , with SX producing significantly greater pre-exercise bronchodilation than CR ( P = 0.04 ) . Following CR , there were no significant differences from the pretreatment values for VO2 , VE , respiratory exchange ratio , heart rate , ventilatory equivalents for VO2 , and oxygen pulse during the submaximal exercise challenge . Following SX , there were no significant differences for any of the exercise variables except for VE at 6 and 12 h ( mean increase 4.27 l min-1 at 6 h , P < 0.01 and 4.69 l min-1 at 12 h , P = 0.05 ) . The changes in ventilation following SX did not have an effect on oxygen consumption , and the ventilatory efficiency ( VE/VO2 ) remained unchanged . The findings from this study demonstrate that , despite exercising from a higher baseline FEV1 , short pretreatment periods with controlled release oral salbutamol and with inhaled salmeterol do not confer any cardiorespiratory advantage during submaximal exercise in subjects with EIA Bronchospasm can be induced in asthmatics when exercised according to a multistage branching treadmill protocol that allows them to achieve 80 per cent of maximal age-predicted heart rate . This degree of exercise is usually achievable and allows inducible bronchospasm to occur . This present study was undertaken to investigate the effect of terbutaline sulfate aerosol in exercise-induced broncho-spasm .  Asthmatics were exercised to 80 per cent of their maximal heart rate , and FEV1.0 and MMEFR were assessed while st and ing using a Jones Pulmonar II waterless spirometer at 5 , 15 , and 30 minutes after exercise . After a st and ard rest period defined by a return to baseline of FEV1.0 , MMEFR , and heart rate for 30 minutes , the subjects were administered either 0.50 mg aerosolized terbutaline sulfate or placebo and then exercised again . The pulmonary function parameters were again recorded after this exercise . Preterbutaline and postplacebo exercise result ed in a significant reduction in FEV1.0 and MMEFR , while after treatment with terbutaline not only did bronchospasm not occur but bronchodilation occurred ( P less than 0.01 ) . Inhaled terbutaline appeared to normalize the exercise tolerance of the asthmatics and restore physiologic pulmonary airway conductance according to the parameters of FEV1.0 and MMEFR A double blind study of 5 asthmatic subjects in remission demonstrated that the severity of bronchoconstriction after exercise was decreased by a single oral dose of 5 mg of terbutaline . The effect lasted for at least 6 hours and was significantly better than the protection afforded by 20 mg of metaproterenol , which was itself more effective than a placebo . In these doses , neither terbutaline nor metaproterenol affected heart rate or blood pressure at rest or in exercise , and no drug-induced side effects were found 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 . FEV , 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 ( FEVj ) 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 < 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 β2‐agonists BACKGROUND AND OBJECTIVE It has been previously established that montelukast provides protection against exercise-induced bronchoconstriction ( EIB ) after a single dose . The present objective was to assess the onset and duration of this protective action in a trial that included both positive and negative controls . METHODS A r and omized , active-controlled and placebo-controlled , double-blind , double-dummy , three-way crossover study was conducted in 47 patients ( age range , 15 to 44 years ) in whom there was a 20 to 40 % fall in FEV(1 ) following exercise ( DeltaFEV(1 ) ) . In r and omized sequence , patients received oral montelukast ( 10 mg ) , placebo , or inhaled salmeterol ( 50 microg ) as a positive control . Dosing was followed by exercise challenges at 2 , 8.5 , and 24 h. The primary end point was maximum DeltaFEV(1 ) at 2 h postdose . Secondary end points included maximum DeltaFEV(1 ) at the two later time points , and other measures ( including recovery time and need for beta-agonist rescue ) at all time points . RESULTS The maximum DeltaFEV(1 ) magnitudes at 2 , 8.5 , and 24 h were significantly smaller after montelukast administration than after placebo administration ( least squares mean [ + /- SE ] , 13.2 + /- 1.2 % , 11.7 + /- 1.2 % , and 10.0 + /- 1.1 % vs 21.8 + /- 1.2 % , 16.8 + /- 1.3 % , and 14.0 + /- 1.1 % , respectively ; p < or= 0.001 , < 0.01 , and < 0.05 ) . All secondary end point results supported the primary end point . Montelukast and salmeterol had similar efficacy at 2 and 8.5 h , but only montelukast was effective at 24 h. CONCLUSION Montelukast provided significant protection against EIB having an onset within 2 h following a single oral dose and lasting for at least 24 In asthma , adrenergic agonists alleviate airflow obstruction and prevent obstructive responses to a variety of stimuli . A rapidly and a slowly metabolized agonist were compared to determine whether bronchodilation is the major mechanism by which these drugs prevent exercise‐induced asthma ( EIA ) . A 200‐µg inhaled dose of the rapidly metabolized agonist , isoproterenol , induced bronchodilation of the same order as terbutaline 500 µg ( I‐sec forced expiratory volume [ FEV1 ] increased 9.5 % and 10.2 % ) . An hour after isoproterenol  , FEV1 was still above baseline ( p < 0.02 ) , but EIA was only partially inhibited ; the 23 % fall in FEV1 was of the same order as the 32 % fall after placebo ( p > 0.05 ) . One hour after terbutaline  , mean resting FEV1 was in the range of that after isoproterenol , but the 10 % change after exercise was less than that after placebo and isoproterenol ( p < 0.005 ) . Our findings suggest that the two effects have different dose‐response relationships , with higher doses of adrenergic agonists needed to prevent EIA than to maintain bronchodilation A double-blind controlled study is reported of salmefamol 200 mug and salbutamol 200 mug administered by aerosol before exercise tests in asthmatic children . Both drugs prevented exercise-induced asthma . There was no significant difference between them A comparative , double-blind , cross-over trial of aminophylline ( 6 mg/kg i.v . ) and salbutamol ( 200 mcg per inhalationem ) was conducted in six male patients ( 20 to 46 years ) with exercise-induced asthma ( EIA ) . Both aminophylline and salbutamol successfully prevented EIA . The serum concentration of theophylline was within the normal range ( 9.8 - -20.3 mcg/ml ) . The effect of salbutamol was slightly more pronounced than the effect of aminophylline but not statistically significant . Because of the more convenient method of application , the authors give priority to salbutamol in the prevention of EIA Exercise-induced asthma is a useful model for evaluating the activity and duration of action of pharmacologic agents of asthma . The main objective of this double-blind , crossover study was to determine the effect of the aerosolized beta-adrenergic agent , bitolterol mesylate , on exercise-induced asthma while its efficacy was being compared with isoproterenol and placebo .  Twelve subjects with exercise-induced asthma performed cycloergometer exercise 45 minutes after three inhalations of bitolterol mesylate aerosol ( 1050 micrograms ) , or isoproterenol ( 255 micrograms ) , or placebo in r and om sequence . Bitolterol mesylate aerosol was very effective in protecting against exercise-induced asthma . The mean percent maximal decrease of FEV1 after exercise was 5.0 % for bitolterol , 22.2 % for isoproterenol , and 23.2 % for placebo . Subjects experienced skeletal muscle tremor with both bitolterol mesylate ( four subjects ) and isoproterenol ( three subjects ) , but not with placebo . No other side effects were noted OBJECTIVES To evaluate the effect of montelukast , 5 mg , or inhaled salmeterol , 50 microg , added to inhaled fluticasone in reducing the maximum percentage decrease in forced expiratory volume in 1 second ( FEV1 ) after a st and ardized exercise challenge and response to rescue bronchodilation with albuterol in children aged 6 to 14 years with persistent asthma and exercise-induced bronchoconstriction ( EIB ) . METHODS R and omized , double-blind , double-dummy , multicenter , 2-period , 4-week , crossover study conducted between December 22 , 2005 and November 14 , 2008 at 30 centers in Europe , Asia , Mexico , and South America . Patients with asthma receiving inhaled corticosteroids  demonstrated an FEV1 of 70 % or higher of the predicted value and EIB ( defined as a decrease in FEV1 > or = 15 % compared with preexercise baseline FEV1 on 2 occasions before r and omization ) . St and ardized exercise challenges were performed at baseline ( prer and omization ) and at the end of each active treatment period . RESULTS Of 154 patients r and omized , 145 completed the study .  Montelukast , compared with salmeterol , significantly reduced the mean maximum percentage decrease in FEV1 ( 10.6 % vs 13.8 % ; P = .009 ) , mean area under the curve for the first 20 minutes after exercise ( 116.0 % x min vs 168.8 % x min ; P = .006 ) , and median time to recovery ( 6.0 vs 11.1 minutes ; P = .04 ) . Response to albuterol rescue after exercise challenge was significantly greater ( P < .001 ) with montelukast . Montelukast and salmeterol were generally well tolerated . CONCLUSIONS Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment RATIONALE Exercise is a common trigger in children with persistent asthma and inhaled corticosteroids have been shown to effectively treat clinical manifestations of persistent asthma , including protection from decrements in lung function caused by exercise . The goal of this study was to evaluate the effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with fluticasone propionate 100 mcg for the prevention of airflow limitation triggered by st and ardized exercise challenge in pediatric and adolescent patients with persistent asthma . METHODS Multicenter , r and omized , double-blind , parallel group trial of 248 subjects with persistent asthma ( age 4 - 17 years ) r and omized to receive fluticasone propionate/salmeterol ( 100/50 mcg twice daily ) or fluticasone propionate alone ( 100 mcg twice daily ) via Diskus for 4 weeks . Exercise challenge tests were performed during screening and approximately 8 hr after administration of the blinded study medication on Treatment Day 28 . RESULTS After 4 weeks of therapy both treatments provided protection following exercise challenge . The protection estimated by the maximal fall in FEV(1 ) was significantly better for fluticasone propionate/salmeterol ( 9.5 + /- 0.8 % [ mean + /- SE ] ) compared with fluticasone propionate alone ( 12.7 + /- 1.1 % , P = 0.021 ) . Statistically significant differences were not observed for asthma rescue-free days and asthma symptom-free days . CONCLUSION Chronic dosing with fluticasone propionate/salmeterol in a single device provides superior protection compared with an inhaled corticosteroid alone in protecting against exercise-induced asthma in children with persistent asthma The effectiveness of inhaled fenoterol doses of 0.4 mg and 0.8 mg in preventing  exercise-induced asthma  was investigated in 12 patients .  Exercise-induced asthma was prevented by both doses for two hours after administration , but the effect of neither dose was significantly different from that of placebo four hours after . There was no statistically significant difference between the effects of the two fenoterol doses ; and only a few patients were protected for more than two hours by the higher dose BACKGROUND Exercise-induced bronchospasm ( EIB ) is a common problem in children with asthma . Pretreatment with the beta2 ( beta 2)-adrenoreceptor agonist albuterol is effective for preventing EIB , but is recognized as providing only short-term ( 2 to 3 hour ) protection . OBJECTIVE To evaluate the 12-hour efficacy and safety of single doses of 25 micrograms and 50 micrograms of salmeterol powder administered via Diskus inhaler versus albuterol aerosol via pressurized metered-dose inhaler and placebo in preventing EIB in asthmatic children . METHODS A r and omized , double-blind , placebo-controlled , double-dummy , single-dose , four-way crossover study was conducted in pediatric patients ( 4 to 11 years of age ) demonstrating EIB and mild-to-moderate asthma .  Serial forced expiratory volume in 1 second ( FEV1 ) was measured before and after st and ard treadmill exercise at hour 1 , hour 6 , and hour 12 after administration of 25 micrograms or 50 micrograms salmeterol powder , 180 micrograms albuterol aerosol , or placebo .  Adverse events were recorded . RESULTS After completion of the hour 1 exercise challenge , mean minimum % predicted FEV1 was significantly higher following albuterol ( 91.3 % ) than for placebo ( 75.3 % ) and for both dosages of salmeterol ( 86.9 % and 85.8 % for salmeterol 25 micrograms and 50 micrograms , respectively ; P < or = .026 ) . After completion of both the hour 6 and hour 12 exercise challenges , the 50-microgram salmeterol treatment produced a significantly higher mean minimum percent of predicted FEV1 ( 90.6 % and 87.3 % predicted , respectively ) than the mean minimum percent of predicted FEV1 for placebo or albuterol ( 73.8 % to 78.4 % of predicted ; P < or = .041 ) . At hour 6 , the 25-microgram salmeterol treatment was not significantly different from albuterol or placebo . At hour 12 , the 25-microgram salmeterol treatment mean minimum percent of predicted was significantly higher than albuterol ( 87.9 % versus 73.8 % of predicted ; P = .006 ) and there was also a trend toward significance over placebo ( 76.9 % predicted ; P = .056 ) . At all exercise periods , no statistically significant differences in spirometry values were observed between the two salmeterol treatment groups . Safety profiles were similar among treatments , including placebo . No drug-related adverse events or withdrawals due to adverse events occurred . Changes in laboratory values , vital signs , 12-lead ECGs , and physical examinations were unremarkable . CONCLUSIONS A single 50-microgram dose of salmeterol powder provided effective and safe protection against EIB for at least 12 hours in asthmatic children and provided a significantly more prolonged effect than albuterol aerosol ( 180 micrograms ) In fifteen patients with asthma  tulobuterol , a new beta 2-adrenoceptor agonist , given by inhalation in 100 micrograms increments up to a cumulative dose of 600 micrograms produced dose related increases in both the FEV1 and FVC . The bronchodilation was observed within 5 min of the first dose . In a further nine patients tulobuterol 200 micrograms and 400 micrograms aerosol inhibited exercise-induced asthma following 6 - 8 min treadmill exercise and the effect was comparable to 200 micrograms salbutamol aerosol . Minor muscle tremors were observed in two patients with 400 micrograms of tulobuterol but no significant changes in pulse rate or blood pressure were noted BACKGROUND The protective effect of a new long acting beta 2-agonist , salmeterol , against exercise-induced bronchoconstriction has been documented when given as inhaled aerosol . OBJECTIVE The aim of the present study was to examine the duration of the protective effect of a single dose of salmeterol , 50 micrograms , inhaled as dry powder , against exercise-induced bronchoconstriction . METHODS Sixteen patients with reproducible exercise-induced bronchoconstriction were challenged on a treadmill on two pre study visits and six study days . The patients were challenged 4 , 8 , and 12 hours postdosing . The study was design ed as a double blind placebo-controlled r and omized crossover trial . RESULTS Statistically significant differences in % maximum fall in PEFR were found at four and eight hours postdosing , in favor of salmeterol . At 12 hours postdosing , no clear statistical inference was possible , owing to the presence of a statistical carry-over effect ; however , significant differences in area under curve in favor of salmeterol were found at 4 , 8 , and 12 hours postdosing . CONCLUSION Salmeterol , 50 micrograms , dry powder inhalation had a protective effect against exercise-induced bronchoconstriction up to 12 hours postdosing , as compared with placebo . No adverse effects were identified A study was performed to investigate changes in plasma cyclic adenosine monophosphate ( cyclic AMP ) , peak expiratory flow and arterial blood gas tensions in response to running exercise and terbutaline sulphate aerosol in asthmatic patients regularly receiving sympathomimetic bronchodilator aerosols . Seven normal subjects were controls .  Placebo aerosol was administered 20 min before the first exercise study and 1.0 - 1.25 mg terbutaline sulphate substituted 20 min after the first test and again 20 min before the second test . Blood gas tensions , expiratory flow and cyclic AMP were measured at rest , during and after exercise . Exercise induced a significant increase in cyclic AMP in both asthmatic and normal subjects . The change in plasma levels was not significantly different between groups . Cyclic AMP values were higher at rest and during exercise with terbutaline sulphate compared with placebo for both groups . Terbutaline sulphate blocked the marked fall in peak expiratory flow and arterial oxygen tension observed in the asthmatic subjects following the first test . Values for cyclic AMP following exercise were not significantly different between asthmatic and normal subjects . In contrast to other reports our asthmatics have a marked increase in cyclic AMP in response to exercise and to a beta-sympathomimetic aerosol INTRODUCTION During the 1970s , scientists suggested that the growing use of chlorofluorocarbons ( CFCs ) was contributing to depletion of the stratospheric ozone layer with potentially harmful results . A committee on the ozone layer organized the preparation of the Montreal Protocol . This protocol m and ated the cessation of production and use of CFCs by January 1 , 1996 . The primary exemption to this ban is for the use of CFCs as propellants in metered dose inhalers ( MDIs ) for the treatment of asthma . Suitable replacement hydrofluoroalkane ( HFA ) propellants , such as HFA-134a , for use in MDIs have been identified . Albuterol , a selective beta-adrenergic agonist , currently widely available for inhalation asthma therapy , has been reformulated in HFA-134a ( Proventil HFA ) . OBJECTIVE ; To compare the efficacy of Proventil HFA to Ventolin , Proventil , and placebo ( HFA-134a ) MDI in protecting asthmatic patients from exercise-induced bronchoconstriction . METHODS This was a r and omized , single-blind , placebo-controlled , 4-period crossover study of asthmatic patients with documented exercise-induced broncho-constriction . Twenty patients self administered two puffs of either Proventil HFA , Ventolin , Proventil or placebo , from an MDI , 30 minutes prior to performing a st and ardized exercise challenge at the study site . Spirometry was performed predose and 5 , 10 , 15 , 30 , 45 , 60 , 75 , and 90 minutes after completion of the exercise challenge . Heart rate and blood pressure were measured just prior to spirometry and a 12-lead ECG was performed 15 minutes after completion of the exercise challenge for measurement of the QT corrected interval . RESULTS The primary efficacy variable was the smallest percent change from the predose FEV1 following exercise . The smallest percent change from predose FEV1 for Proventil HFA was 2.0 + /- 9.9 SD , similar to the 2.0 + /- 11.4 SD for Ventolin , and the 3.6 + /- 10.2 SD for Proventil . The smallest percent change from predose FEV1 for each of the active treatments was significantly different from placebo , -23.7 + /- 14.5 . Twelve of the patients had a > or = 20 % fall in FEV1 post-exercise with placebo pretreatment , but only 1 , 1 , and 0 had > or = 20 % FEV1 falls after treatment with Proventil HFA , Ventolin , and Proventil respectively . Changes in heart rate , blood pressure and QT corrected interval were similar for the three active treatments following exercise . CONCLUSIONS Proventil HFA provides protection against exercise-induced bronchoconstriction comparable to Ventolin and Proventil and protection superior to placebo . Proventil HFA has a safety profile similar to Ventolin when used to prevent exercise-induced bronchoconstriction BACKGROUND Exercise is a common trigger of asthma symptoms in patients with persistent asthma . OBJECTIVE To evaluate the protective effect of fluticasone/salmeterol against exercise-induced bronchospasm . METHODS Multicenter , r and omized , double-blind , parallel-group trial of 192 asthma patients who used moderate-dose inhaled corticosteroids . Patients ( aged 12 - 50 years ; mean forced expiratory volume in 1 second [ FEV1 ] , 78 % of predicted at baseline ) were r and omized to receive fluticasone/salmeterol ( 250/50 microg twice daily ) or fluticasone alone ( 250 microg twice daily ) via Diskus for 4 weeks . Exercise challenge tests were performed 1 and 8.5 hours after administration of the first ( day 1 ) and last ( week 4 ) doses of blinded study medication . RESULTS On day 1 and at week 4 , mean + /- SEM values for the maximal percentage decline in FEV1 1 hour after drug administration were 11.4 % + /- 1.5 % and 10.9 % + /- 1.5 % for fluticasone/salmeterol compared with 20.0 % + /- 1.7 % and 18.4 % + /- 1.8 % for fluticasone ( P < .001 ) . At 8.5 hours , mean + /- SEM values on day 1 and at week 4 were 11.6 % + /- 1.4 % and 8.9 % + /1.1 % , respectively , for fluticasone/salmeterol and 12.6 % + /- 1.6 % and 12.9 % + /- 1.4 % , respectively , for fluticasone ( P = .01 at week 4 ) . More fluticasone-treated patients did not complete the 8.5-hour exercise challenges ( 36 % on day 1 and 33 % at week 4 ) compared with the fluticasone/salmeterol group ( 18 % each ) ( P < or = .01 ) . Improvements in peak expiratory flow rate and albuterol rescue-free days were significantly greater with fluticasone/salmeterol vs fluticasone over weeks 1 to 4 ( P < or = .03 ) . CONCLUSIONS Consistent with the improvements in other measures of asthma control , long-term fluticasone/salmeterol therapy also provided protection against exercise-induced bronchospasm in patients with persistent asthma STUDY OBJECTIVE To compare the safety of salmeterol xinafoate or placebo added to usual asthma care . DESIGN A 28-week , r and omized , double-blind , placebo-controlled , observational study . SETTING Study subjects were seen once in the study physician 's office for screening and were provided all blinded study medication for the entire study period . Follow-up by telephone was scheduled every 4 weeks . PARTICIPANTS Subjects ( > 12 years old ) with asthma as judged by the study physician were eligible . Individuals with a history of long-acting beta2-agonist use were excluded . INTERVENTIONS Salmeterol , 42 mug bid via metered-dose inhaler ( MDI ) , and placebo bid via MDI . MEASUREMENTS AND RESULTS Following an interim analysis in 26,355 subjects , the study was terminated due to findings in African Americans and difficulties in enrollment . The occurrence of the primary outcome , respiratory-related deaths , or life-threatening experiences was low and not significantly different for salmeterol vs placebo ( 50 vs 36 ; relative risk [ RR ] = 1.40 ; 95 % confidence interval [ CI ] , 0.91 to 2.14 ) . There was a small , significant increase in respiratory-related deaths ( 24 vs 11 ; RR , 2.16 ; 95 % CI , 1.06 to 4.41 ) and asthma-related deaths ( 13 vs 3 ; RR , 4.37 ; 95 % CI , 1.25 to 15.34 ) , and in combined asthma-related deaths or life-threatening experiences ( 37 vs 22 ; RR , 1.71 ; 95 % CI , 1.01 to 2.89 ) in subjects receiving salmeterol vs placebo . The imbalance occurred largely in the African-American sub population : respiratory-related deaths or life-threatening experiences ( 20 vs 5 ; RR , 4.10 ; 95 % CI , 1.54 to 10.90 ) and combined asthma-related deaths or life-threatening experiences ( 19 vs 4 ; RR , 4.92 ; 95 % CI , 1.68 to 14.45 ) in subjects receiving salmeterol vs placebo . CONCLUSIONS For the primary end point in the total population , there were no significant differences between treatments . There were small , but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol . Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects . Whether this risk is due to factors including but not limited to a physiologic treatment effect , genetic factors , or patient behaviors leading to poor outcomes remains unknown The effect of 40 microgram of SCH 1000 ( ipratropium bromide , an anticholinergic agent ) on bronchodilation and suppression of exercise-induced bronchospasm ( EIB ) was compared with 400 microgram of fenoterol and a placebo in a single-blind controlled study . Twenty-seven r and omly selected asthmatic children performed a st and ardized treadmill exercise challenge and the 17 children who were shown to have EIB continued in the study .  Pulmonary function was evaluated before and after drug administration and exercise . When individual results were analyzed and grouped according to the responsiveness of EIB to the drugs , two patterns emerged : ( 1 ) the EIB was more severe in those ( 6/17 ) children who did not respond to either drug than in the rest of children ; ( 2 ) the resting pulmonary function was significantly better in the children ( 4/17 ) who responded to both drugs than in those ( 7/17 ) who responded to fenoterol alone . In conclusion SCH 1000 was shown to be an effective bronchodilator comparable to , but no better than , fenoterol . It had minimal side effects . As an EIB inhibitor it depended on relatively normal base line pulmonary function and only a moderate deterioration following exercise , whereas fenoterol depended on the exercise response alone . Although anticholinergic drugs are not very extensively used , SCH 1000 may be useful in some patients where the beta 2 adrenergic drugs cause signficant side effects or are contraindicated OBJECTIVES To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids ( ICS ) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction . METHODS A double-blind , placebo-controlled study was performed at 16 centers in the United States . Patients with asthma ( n = 122 , ages 15 - 58 ) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were r and omized to receive either montelukast ( 10 mg once daily ) , salmeterol ( 50microg twice daily ) , or placebo for 4 weeks . St and ardized spirometry  after exercise challenge and beta2-agonist rescue was performed at baseline , week 1 and 4 . RESULTS Maximum achievable forced expiratory volume in 1 s ( FEV1 ) percent predicted after rescue beta2-agonist improved in the montelukast ( + 1.5 % ) and placebo ( + 1.2 % ) groups at 4 weeks , but diminished in the salmeterol ( -3.9 % ) group ( P < 0.001 ) . Although pre-exercise FEV1 was greatest with salmeterol ( P = 0.10 ) , patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol ( P < 0.001 ) . Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol ( P < 0.001 ) . Five minutes after rescue beta2-agonist , 92 % of patients taking montelukast and 68 % of those taking placebo had recovered to pre-exercise levels , whereas only 50 % of those taking salmeterol had recovered to pre-exercise levels . CONCLUSION In patients whose asthma symptoms remain uncontrolled using ICS , addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinical ly meaningful protection against exercise-induced bronchoconstriction BACKGROUND Patients with exercise-induced bronchospasm ( EIB ) may benefit from a prophylactic beta2-adrenergic agonist that combines rapid onset with long duration of action . OBJECTIVE To compare the protective effect against EIB of a single inhaled dose of formoterol powder delivered via the Aerolizer inhaler ( Novartis Pharmaceuticals , East Hanover , NJ ) with the effect of placebo and albuterol . METHODS Eighteen patients with EIB were r and omized to treatment in a double-blind , placebo-controlled , four-way , crossover study . Seventeen patients completed all four crossover periods . Each patient received in r and om sequence a single dose of formoterol ( 12 or 24 microg ) , albuterol ( 180 microg ) , or placebo at intervals of 5 + /- 2 days . Pulmonary function measurements were taken before and after exercise challenge tests ( ECTs ) at 15 minutes postdosing and at 4 , 8 , and 12 hours postdosing . RESULTS Both doses of formoterol produced significantly greater protection against EIB , compared with placebo , at all timepoints ( P < or = 0.016 ) . The two doses of formoterol were not significantly different from one another at any time . Protection against EIB with albuterol was clinical ly significant only for the 15-minute ECT and was statistically superior to placebo for the 15-minute and 4-hour ECTs . Although formoterol and albuterol exhibited a rapid onset of action , formoterol provided longer-lasting protection over the 12-hour observation period . Rescue medication was used substantially less with either dose of formoterol , compared with albuterol or placebo . All treatments were well tolerated . Two-hour postdosing electrocardiograms and vital signs were unremarkable for all study treatments . CONCLUSION A single dose of formoterol ( 12 or 24 microg ) provides protection against EIB within 15 minutes of dosing and persists for up to 12 hours . Formoterol is safe and well tolerated The effects of inhaled terbutaline , a β2-adrenergic agonist , administered via a 750-ml spacer device were studied in young asthmatic subjects with exercise-induced asthma . A double-blind , r and omized , placebo-controlled study of the effects of inhaled 0.5 mg terbutaline and placebo was conducted in 10 asthmatic children ( age range 6–16 years ) with documented exercise-induced asthma . Forced expiratory volume in 1 s ( FEV1 ) was measured at baseline , 15 min after inhaling terbutaline or placebo , and at intervals up to 60 min after exercising . Subjects exercised using a cycle ergometer for 5 min at a submaximal , constant work-load while breathing dry air at room temperature . Terbutaline induced bronchodilation at rest in all subject and fully prevented exercise-induced asthma in nine out of the 10 subjects ; the exercise-induced fall in FEV1 was markedly reduced in the remaining subject . It is concluded that exercise-induced asthma can be inhibited by pretreatment with inhaled terbutaline , administered via a spacer , in a majority of young asthmatics Clenbuterol ( C ) , a long-acting beta 2-selective bronchodilator was compared with salbutamol ( S ) in exercise-induced asthma ( EIA ) at two premedication time levels . Sixteen asthmatic children with EIA living at an altitude of 1,750 m were treated with C ( 0.001 mg/kg ) and S ( 0.12 mg/kg ) , administered r and omly in a double-blind cross-over study 90 and 300 minutes before exercise tests of running on a treadmill for 6 minutes .  Pulmonary functions were evaluated prior to the administration of the drugs and immediately before , at the end of , and 2 , 5 , 10 , 15 , 20 , and 25 minutes after exercise tests . In the preliminary screening exercise test the mean fall of FEV1 was 41.1 % , but it was 21.0 % and 27.1 % after S and 21.9 % and 19.9 % after C administered 90 and 300 min prior to the test , respectively . Salbutamol administered 300 minutes before the test was statistically less effective than the same drug administered 90 minutes before the test or C administered 300 minutes before the test . Therefore , we can conclude that clenbuterol provides a more lasting protection than salbutamol in EIA 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 r and omized , 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 Silverman , M. , Konig , P. , and Godfrey , S. (1973).Thorax , 28 , 574 - 578 . Use of serial exercise tests to assess the efficacy and duration of action of drugs for asthma . A technique for study ing the efficacy and duration of action of drugs used in asthma by means of exercise tests is described . The patient runs for six minutes every two hours , four times a day , on a treadmill at a constant speed and slope . The test drug or its placebo is given immediately before the first test of the day , and their effects on the exercise-induced asthma are compared . This enables the immediate protection and duration of action of the test drug to be measured . No change in the severity of post-exercise asthma was found when serial tests were performed during one day after administration of a placebo . In a selected group of 14 children studied with disodium cromoglycate , three patterns were seen . In five patients the drug afforded prolonged benefit , in five others the protection was very short-lived , and in four patients it did not seem to be better than the placebo . The use of the tests is also illustrated with respect to bronchodilator drugs PURPOSE The purpose of this study was to compare a laboratory based exercise challenge ( LBC ) to a field based exercise challenge ( FBC ) for pulmonary function test ( PFT ) exercise-induced asthma ( EIA ) screening of elite athletes . METHODS Twenty-three elite cold weather athletes ( 14 men , 9 women ) PFT positive for EIA ( FBC screened ) served as subjects . Twenty-three gender and sport matched controls ( nonasthmatics ) were r and omly selected to establish PFT reference values for normal elite athletes . Before FBC , athletes completed a medical history question naire for EIA symptoms . FBC evaluations consisted of baseline spirometry , actual or simulated competition , and 5 , 10 , and 15 min postexercise spirometry . PFT positive athletes were evaluated in the laboratory using an exercise challenge simulating race intensity ( ambient conditions : 21 degrees C , 60 % relative humidity ) . PFT procedures were identical to FBC . RESULTS 91 % of PFT positive and 48 % of PFT normal athletes reported at least one symptom of EIA , with postrace cough most frequent . Baseline spirometry was the same for PFT positives and normal controls . Lower limit reference range ( MN - 2 SD ) of FEV1 for controls suggests that postexercise decrements of greater than approximately -7 % indicate abnormal airway response in this population . Exercise time duration did not effect bronchial reactivity ; 78 % of FBC PFT positives were PFT normal post-LBC . CONCLUSION Self-reported symptoms by elite athletes are not reliable in identifying EIA . Reference range criterion for FEV1 decrement in the elite athlete postexercise contrasts current recommended guidelines . Moreover , a large number of false negatives may occur in this population if EIA screening is performed with inadequate exercise and environmental stress The effects of oral doses of theophylline and a beta-adrenergic agonist , fenoterol , were examined in 18 asthmatic young adults . Significant bronchodilation was seen with high-dose theophylline ( FEV1 increased 14 percent ) and with full 10-mg doses of fenoterol ( FEV1 increased 10 percent ) . Low-dose theophylline alone ( 130 mg ) increased FEV1 by 5 percent , but when combined with 5 mg of fenoterol , a 14 percent improvement was seen , demonstrating significant ( P = .003 ) additive effects . The ability of the two drugs to prevent the asthmatic response to exercise was not additive . The mean fall in FEV1 was not statistically different when subjects exercised after receiving a placebo ( 32 percent ) 130 mg of theophylline ( 27 percent ) , or 130 mg of theophylline with 5 mg of fenoterol ( 18 percent ) . Furthermore , side effects associated with the two drugs , such as tachycardia , tremor , or CNS stimulation , were significantly increased when the two drugs were given simultaneously . Thus , little therapeutic benefit was gained from simultaneous therapy . Both bronchodilation and toxicity were equivalent to that seen with larger therapeutic doses of either drug given alone , and protection from the effects of a frequently encountered stress was not significantly enhanced Theophylline and terbutaline , alone and in combination , were evaluated for effectiveness in treating  exercise-induced bronchospasm ( EIB )  when used at doses that should be tolerated by adolescents taking them intermittently : theophylline , 250 mg ( fast release ) and terbutaline , 2.5 mg . Twenty-one subjects , 12 to 19 years of age , with EIB performed st and ardized exercise tests on four separate days and received either theophylline , terbutaline , the combination , or placebo in a prer and omized double-blind manner prior to exercise . Exercise tests were performed two and five hours after each study drug administration . Blood sample s were drawn before and again two and five hours after drug administration for theophylline level . Pulmonary function [ forced vital capacity ( FVC ) , forced expiratory volume in one second ( FEV1 ) , and forced expiratory flow rate ( FEF 25 % to 75 % ) ] was recorded before and after exercise . All of the active treatments were better than placebo in diminishing EIB . The combination was statistically better than terbutaline or theophylline alone . The effect of theophylline was not significantly different from that of terbutaline . The combination induced significantly more tremor than either agent individually . Either drug alone or the two in combination is effective for diminishing EIB . Although the combination may have additive properties for some patients , the increased incidence of tremor may diminish its appeal . Either drug alone or in combination is effective in decreasing EIB for at least five hours , which makes them practical choices for treatment of school-aged children The potential for rimiterol to protect athletes from exercise-induced asthma ( EIA ) has not been fully established . Ten athletes with asthma ( 15 to 30 years of age ) undertook 8 minutes of submaximal exercise ( 80 % of anaerobic threshold ) on the treadmill ergometer , once after inhaling rimiterol and once after inhaling a placebo . Treatment with all bronchodilator drugs was stopped for the 12 hours preceding each exercise test . Two puffs ( 400 micrograms ) of rimiterol or placebo were administered in a double-blind crossover manner 2 minutes before each exercise test . Lung function measurements were made before exercise and immediately , 5 , 10 , 15 , 20 , 25 , and 30 minutes after completion of exercise . The results of a two-way analysis of variance revealed significant ( p less than 0.01 ) difference in the FEV1 scores obtained after rimiterol inhalation and placebo inhalation , 5 , 10 , 15 , 20 , 25 , and 30 minutes after cessation of exercise . After inhalation of rimiterol , there were no significant changes in FEV1 . After inhaling the placebo , significant reductions ( p less than 0.01 ) in FEV1 occurred after cessation of exercise ( 5 , 10 , 15 , and 20 minutes ) . All subjects exhibited EIA after placebo , and none after rimiterol . The mean maximum drop after exercise in FEV1 after inhalation of rimiterol ( 2.807 + /- 5.55 ) and placebo ( 24.54 + /- 8.4 ) was significantly different ( t = 6.849 ) . It was concluded that inhalation of rimiterol 2 minutes before exercise afforded significant protection from EIA in all subjects tested The magnitude and duration of protection against exercise-induced asthma ( EIA ) afforded by salbutamol and the new , long-acting beta 2-agonist , formoterol , were compared in a double-blind , placebo-controlled crossover study . Twelve children with asthma and EIA ( greater than 25 % fall from baseline at a pretrial exercise test ) were studied on 3 different days receiving , in r and om order , either formoterol , 12 micrograms , salbutamol , 200 micrograms , or placebo by inhalation . The effect on EIA was evaluated by st and ardized treadmill-exercise tests repeated at the following times after medication : 1/2 hour ( test 1 ) , 3 hours ( test 2 ) , and , if the trial drug still demonstrated an effect , 5 1/2 hours ( test 3 ) and 8 hours ( test 4 ) . The mean ( SD ) maximum percent fall in FEV1 at the pretrial test was 45 % ( 14 % ) . Placebo treatment had no effect on EIA . The mean ( SD ) maximum percent fall in FEV1 was 44 % ( 14 % ) ( test 1 ) and 39 % ( 13 % ) ( test 2 ) ( not significant ) . Salbutamol offered good protection against EIA after 1/2 hour ( percent fall in FEV1 , 18 % [ 18 % ] ; p less than 0.02 ) but was not significantly different from that of placebo after 3 hours , 39 % ( 13 % ) fall in FEV1 . Formoterol blocked EIA in all the children and demonstrated a significant effect in most children for at least 8 hours . The percent fall in FEV1 after the various tests were 8 % ( 16 % ) ( test 1 ) , 10 % ( 9 % ) ( test 2 ) , 18 % ( 15 % ) ( test 3 ) , and 18 % ( 7 % ) ( test 4 ; N = 9 ) ( all tests , p less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The effects of the beta 2-adrenergic agonist salbutamol ( 0.02 mL/kg of a 0.5 % solution ) and the cholinergic antagonist ipratropium bromide ( 2 mL of a 0.025 % solution ) , administered alone or in combination at different doses , were evaluated in 48 asthmatic children using a single-dose , double-blind , crossover design . Spirometric measurements were taken before and 10 , 30 , 60 , 120 , 180 , 240 , 300 , and 360 minutes after administration of the drugs . All regimens produced significant bronchodilatation 10 to 30 minutes after administration . The improvement began to decline three to four hours after inhalation , particularly when ipratropium bromide was administered alone . The administration of the salbutamol plus ipratropium combination did not significantly improve pulmonary function values as compared to salbutamol alone . The effects of salbutamol and ipratropium bromide in half-dose or full-dose combinations were indistinguishable . No significant adverse effects on blood pressure or heart rate were observed BACKGROUND Inhaled short-acting beta(2)-adrenoceptor agonists are the most commonly used treatment for the prevention of exercise-induced bronchoconstriction ( EIB ) .  Formoterol , a long-acting beta(2)-adrenoceptor agonist , has been demonstrated to provide protection from EIB , although the onset and duration of this protection have not been defined . OBJECTIVE The purpose of this study was to determine the onset and duration of the protective effect of a single dose of inhaled formoterol powder against EIB , comparing them with the effect of a single dose of placebo and albuterol administered via metered-dose inhaler ( MDI ) . METHODS In this double-dummy , 4-way crossover study , patients received single doses of formoterol ( 12 and 24 microg ) via a powder inhaler , albuterol by MDI ( 180 microg ) , and placebo . Exercise challenge tests ( ECTs ) were conducted at 15 minutes and at 4 , 8 , and 12 hours postdose . Pulmonary function studies ( forced expiratory volume in 1 second [ FEV(1 ) ] and peak expiratory flow rate ) were performed before and after each exercise challenge . RESULTS Twenty adolescent and adult patients ( mean age , 23.8 years ; range , 13 - 41 years ; 9 male , 11 female ) with asthma were enrolled in the study , and 17 completed all 4 treatment sequences . Compared with placebo , both doses of formoterol produced significantly greater inhibition of FEV(1 ) decreases at all time points ( P < 0.01 ) . There were no significant differences in efficacy measures between the 2 formoterol doses throughout the study . The exercise-induced decrease in FEV(1 ) after albuterol treatment was significantly reduced compared with placebo only at 15 minutes after dosing ( P < 0.05 ) . Formoterol and albuterol exhibited a similar rapid onset of action ( < 15 minutes ) , but formoterol continued to protect patients against EIB for at least 12 hours ( P < 0.01 ) , whereas albuterol was no longer clinical ly effective by the 4-hour ECT . CONCLUSIONS Formoterol and albuterol , given as single-dose inhalations , both provided protection from EIB within 15 minutes in this group of patients . The bronchoprotection afforded by formoterol lasted up to 12 hours , whereas that of albuterol was no longer significant by 4 hours Twenty-one asthmatic patients participated in a single blind , crossover study comparing the effects of aerosol and oral salbutamol ( a beta-adrenergic bronchodilator ) , on exercise-induced bronchospasm . By both routes of administration , salbutamol ( albuterol ) produced significant bronchodilatation at rest , but only the aerosol effectively prevented post-exercise bronchospasm in most patients . Because exercise-induced bronchospasm is a common problem in children and adults with asthma , these observations are relevant to the drug therapy of these patients . The existence of separate mechanisms for bronchodilatation and the prevention of exercise-induced asthma is postulated . It is possible that differing tissue concentrations of salbutamol are responsible for the observed differences between the 2 routes of administration 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 The prophylaxis of exercise-induced asthma with inhaled formoterol ( 12 micrograms ) was compared with inhaled salbutamol ( 200 micrograms ) and placebo in 12 patients with atopic asthma . Both drugs produced equal bronchodilation 2 and 4 h after administration . Both drugs protected equally against exercise-induced bronchoconstriction 2 h after administration ; at 4 h , formoterol gave undiminished protection from that seen at 2 h while salbutamol was no more effective than placebo The aim of the present study was to verify the effectiveness of procaterol , a recent and specific beta-2-adrenoceptor stimulant , in preventing exercise-induced asthma ( EIA ) . Twelve asthmatic patients were selected aged 18.6 + /- 5.6 years with a positive response to EIA and a basal forced expiratory volume of the first second ( FEV1 ) better than 80 % of predicted . The patients underwent four bronchoprovocation challenges on four consecutive days . On the first day they performed an inclusion test , and , on the three subsequent days , they were su bmi tted , to three identical st and ardized challenges according to a r and omized design . Fifteen minutes before , procaterol ( 20 mcg ) , salbutamol ( 200 mcg ) and a placebo were administered as metered aerosol . No pharmacological treatment was given for 24 h ( 48 h for antihistamines ) before each challenge . The test was carried out running on treadmill ( 10 % grade ) for 7 min . Room temperature ( 20 - 25 degrees C ) and relative humidity ( 40 - 55 % ) were maintained constant . At baseline , 15 min before , 5 , 10 , 15 , 30 and 60 min after the exercise , lung function was assessed . Basal mean values of FEV1 were 94.7 , 94.9 , 90.7 and 91.5 % of predicted for the inclusion and the three protected tests , respectively , without significant differences . The FEV1 mean values showed a mild bronchodilation 15 min after salbutamol ( + 13.2 % , p less than 0.006 ) and procaterol ( + 8 % , NS ) . At every considered time all indices showed a significant gap ( p less than 0.01 ) between drugs and the placebo with no appreciable differences between procaterol and salbutamol The authors have evaluated the effectiveness of the protection of a new beta2-adrenergic compound , reproterol , against broncho-constriction induced by physical exercise in a group of individuals of paediatric age sensitive to broncho-stimulation . This study has been carried out comparing reproterol with salbutamol , using placebo as a control , following a r and omized single-blind crossover trial . The provocation test has been performed following the instructions of the Italian Society of Paediatrics . The drugs have been administered in the oral liquid form at the dose of 0·28 mg/kg and 0·1 mg/kg of reproterol and salbutamol , respectively . The two substances have shown a similar preventive effectiveness in controlling exercise-induced asthma up to 2 hours from administration with reproterol having a stronger action at the beginning of the observation Oral salbutamol in a dose 0.15 mg/kg of body weight was compared to a total dose of 0.2 mg of salbutamol aerosol in its ability to produce bronchodilation and to prevent exercise-induced bronchospasm ( EIB ) in 16 asthmatic children in a single-blind crossover study . The degree of bronchodilation seen 120 minutes after the oral salbutamol was equal to that seen 40 minutes after the salbutamol aerosol as assessed by peak expiratory flow ( PEF ) , forced vital capacity ( FVC ) , forced expiratory volume in 1 second ( FEV1 ) , forced expiratory flow during the middle half of the FVC ( FEF25 - 75 % ) , and maximum expiratory-flow after 75 % of the FVC had been expired ( V25 ) . With respect to changes in PEF and FEV1 , both active agents were equally effective in blocking EIB following a st and ardized treadmill exercise test . However , in assessing changes in FEF25 - 75 % , and V25 following exercise , the aerosol was slightly but significantly more effective than the oral preparation in blocking EIB . Oral salbutamol was clinical ly effective in preventing EIB for 4.9 to 5.8 hours . The aerosol route has the advantages of a faster onset of action , fewer side effects , and greater protection against EIB with respect ot small airways function . Nevertheless , for patients who are unable to use a metered aerosol , oral salbutamol is a useful alternative both as a bronchodilator and in preventing EIB Exercise-induced asthma ( EIA ) is a frequent symptom in asthmatic patients . The study of drugs which inhibit EIA is very important because EIA seriously limits the life of the patients . In addition , this study could allow further insights to be gained into the pathogenesis of the phenomenon . The aim of the present study is to evaluate the duration of the protective effect of fenoterol alone or in combination with ipratropium bromide administered 5 h before exercise . For this purpose we studied 12 asthmatic patients ( 7 males and 5 females , mean age 23 , range 7 - 41 years ) with EIA , in clinical and functional stable state .  Respiratory function parameters were measured before and 5 h after the administration of fenoterol 400 or 200 micrograms , or fenoterol 200 micrograms plus ipratropium bromide 80 micrograms ( Duovent ) , or placebo in r and omized order . Then , such parameters were measured at 5 , 15 , 30 , and 60 min after exercise , which consisted of free running up and down the stairs . The results show that , at 5 h after the administration of each drug , the protective action against EIA is only partial . However , the intense bronchodilation afforded by the ' active ' drugs , and particularly by 400 micrograms of fenoterol , keeps post-exertional respiratory parameters above the baseline values
BACKGROUND It is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma .
International guidelines on asthma management recommend the use of beta2-agonists at any stage of the disease .
At present , however , no consensus has been reached about the efficacy and safety of beta2-agonists in the pretreatment of exercise-induced asthma and exercise-induced bronchoconstriction .
For the purpose of the present review , both of these conditions are referred to by the acronymous EIA , independently from the presence of an underlying chronic clinical disease .
OBJECTIVES To assess the effects of inhaled short- and long-acting beta2-agonists , compared with placebo , in the pretreatment of children and adults with exercise-induced asthma ( or exercise-induced bronchoconstriction ) .