Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma Ipratropium bromide: bronchodilator action and effect on methacholine-induced bronchoconstriction. How long should Atrovent be given in acute asthma? Duration of protection by oxitropium bromide against cholinergic challenge. Use of ipratropium bromide in asthma. Results of a multi-clinic study. [Effectiveness of disodium cromoglycate, salbutamol, and ipratropium bromide in the inhibition of exercise-induced bronchospasm]. Salbutamol and ipratropium in acute asthma. Atropine and exercise-induced bronchoconstriction. Exercise-induced asthma (EIA): its prevention with the combined use of ipratropium bromide and fenoterol. Suppression of exercise-induced asthma by salbutamol, theophylline, atropine, cromolyn, and placebo in a group of asthmatic children. Prolonged effect of inhaled glycopyrrolate in asthma. The effect of ipratropium and fenoterol on methacholine-histamine-induced bronchoconstriction. Effect of nebulized ipratropium bromide on intraocular pressures in children. Efficacy of nebulized ipratropium in severely asthmatic children. Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1–4-year-old children with moderate asthma Protective effects of inhaled ipratropium bromide on bronchoconstriction induced by adenosine and methacholine in asthma. Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children. Inhibition of exercise-induced bronchospasm by atropine. Long-term effect of ipratropium bromide and fenoterol on the bronchial hyperresponsiveness to histamine in children with asthma. Combined therapy with ipratropium and theophylline in asthma. Failure of ipratropium bromide to modify the diurnal variation of asthma in asthmatic children. Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children. Combined treatment with ipratropium bromide and beta-2-adrenoceptor agonists in childhood asthma. Bronchial responsiveness to hyperventilation in children with asthma: inhibition by ipratropium bromide. Prevention of fog-induced bronchospasm by Duovent and its components (fenoterol, ipratropium bromide) in asthmatics. A place for ipratropium bromide in the treatment of severe acute asthma. Ipratropium bromide in acute asthma. The effect of ipratropium on exercise-induced bronchoconstriction. Nebulized salbutamol and ipratropium bromide in asthmatic children. Comparison of the effects of inhaled calcium antagonist verapamil, sodium cromoglycate and ipratropium bromide on exercise-induced bronchoconstriction in children with asthma Aerosol Sch 1000. An anticholinergic bronchodilator. Ipratropium Bromide Added to Asthma Treatment in the Pediatric Emergency Department Combination of atropine and isoetharine aerosol therapy in pediatric acute asthma. Sodium cromoglycate and ipratropium bromide in exercise-induced asthma. Nebulised ipratropium and salbutamol in asthma. Randomised controlled trial of aminophylline for severe acute asthma The addition of an aerosol anticholinergic to an oral beta agonist plus theophylline in asthma and bronchitis. A double-blind single dose study. Inhaled ipratropium bromide and terbutaline in asthmatic children. Effect of Duovent (ipratropium bromide and fenoterol) on non-specific bronchial hyperreactivity. Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma. The role of the parasympathetic nervous system in the maintenance of chronic airway obstruction in asthmatic children. Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma. Bronchodilator effects of clemastine, ipratropium, bromide, and salbutamol in preschool children with asthma. The Effects of Ipratropium Bromide and Fenoterol Nebulizer Solutions in Children with Asthma A randomized, placebo-controlled study to evaluate the role of salmeterol in the in-hospital management of asthma. The protective effects of ipratropium bromide and terbutaline on distilled water-induced bronchoconstriction. Anticholinergic and sympathomimetic combination therapy of asthma. Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma. Time course of methacholine induced bronchoconstriction during drugs and spontaneous resolution. Double-blind study of ipratropium bromide, a new anticholinergic bronchodilator. Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma Prevention of exercise‐induced asthma by drugs inhaled from metered aerosols Additive effect of albuterol and ipratropium bromide in the treatment of bronchospasm in children. Double blind comparison of acute bronchial and ventilation-perfusion changes to atrovent and isoproterenol. Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma. Ipratropium bromide (Atrovent) in childhood asthma: a cumulative dose-response study. Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis. Oxatomide modifies methacholine- and exercise-induced bronchoconstriction in asthmatic children. Comparison of a single dose of aerosol salbutamol and fenoterol/ipratropium on bronchial asthmatic patients. 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Oxatomide and exercise‐induced asthma in children: the value of serial exercise tests Comparison of preservative-free and preservative-containing ipratropium bromide. A random double-blind trial of the combination of nebulized atropine methylnitrate and albuterol in nocturnal asthma. [The effect of inhaling pirenzepine--selective M1 receptor antagonist and ipratropium bromide on lung ventilation in patients with bronchial asthma]. Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial Bronchoconstriction in response to suggestion: its prevention by an inhaled anticholinergic agent. [Evaluation of the bronchodilatory activity of berodual and its components: fenoterol and ipratropium bromide in children with bronchial asthma]. Long term atropine in chronic severe childhood asthma. [Bronchial asthma in childhood. Therapy with fenoterol and ipratropium bromide powder]. Evaluation of Duovent in the prevention of exercise-induced asthma. Blind randomized cross-over comparative study of salbutamol and the combination fenoterol-ipratropium IK6 in patients with bronchial asthma.
Eight patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled lignocaine ( estimated dose 48 mg ) , sodium cromoglycate ( estimated dose 12 mg ) , and ipratropium bromide ( estimated dose 120 μg ) . Saline was used as control . Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second ( FEV1 ) and maximal mid-expiratory flow rates ( MMFR ) after they had run on a treadmill for eight minutes . There was no significant change in baseline FEV1 or MMFR before each agent was given . Saline , lignocaine , and sodium cromoglycate did not alter the mean baseline FEV1 or MMFR significantly .  Ipratropium  caused bronchodilatation with an increase of 16·3 % in the mean FEV1 ( p<0·001 ) and of 43·4 % in the mean MMFR ( p<0·05 ) . After exercise the maximal percentage falls in FEV1 ( means and SEM ) after saline , lignocaine , sodium cromoglycate , and ipratropium bromide were 38·1 % ( 5·0 ) , 34·5 % ( 6·1 ) , 11·3 % ( 3·7 ) , and 19·3 % ( 7·4 ) respectively . Similarly , the mean maximal falls in MMFR  after saline , lignocaine , sodium cromoglycate , and ipratropium bromide were 54·4 % ( 5·2 ) , 52·9 % ( 7·7 ) , 23·6 % ( 6·6 ) , and 32·1 % ( 10·5 ) respectively . The inhibitory  effects of sodium cromoglycate and ipratropium bromide were significant whereas lignocaine failed to produce an effect . These results suggest that mediator release is an important factor in exercise-induced asthma and that in some patients the effects of the mediators may be on the postsynaptic muscarinic receptors . Local anaesthesia of sensory vagal receptors , on the other h and , does not prevent exercise asthma and these receptors do not appear to have any important role in exercise-induced bronchoconstriction The effects of ipratropium bromide ( 80 and 200 micrograms ) and placebo on the basal bronchial tone and on methacholine-induced bronchoconstriction were investigated in 10 asthmatic patients in a placebo-controlled double-blind manner . Bronchial hyperreactivity to methacholine was confirmed at a pretrial bronchial challenge . The patients were r and omly allocated to two groups in which the drug was inhaled from either metered-dose inhalers ( MDI ) or powder capsules . With the high dosage , the bronchodilation result ing from powder capsules was somewhat more pronounced than that achieved with the MDI . Otherwise the bronchodilator effect of ipratropium bromide and the protection afforded by the drug against methacholine-induced bronchoconstriction were similar in the two groups . In five patients the bronchodilator effect was better and in four patients the tolerance to methacholine was greater after the higher ipratropium dosage than after the lower one . In two patients ipratropium bromide had no bronchodilator effect but gave good protection against methacholine-induced bronchoconstriction . It is concluded that some patients benefit from a dosage of ipratropium bromide higher than that usually recommended and that an anticholinergic effect on the bronchi is possible even in the absence of the bronchodilator effect in the basal state BACKGROUND In acute asthma the optimal duration of treatment with combination β agonist and anticholinergic nebuliser solutions is unknown ; most studies have investigated single doses or treatment for up to 12 hours . To determine whether longer treatment with ipratropium bromide might aid recovery a study was undertaken in 106 patients with acute asthma . METHODS A double blind , r and omised , placebo controlled , three group study was performed with all patients receiving ipratropium for 12 hours and salbutamol for 60 hours after admission ( both nebulised four hourly ) , systemic steroids and , if necessary , theophylline . At 12 hours ipratropium was stopped in group I ( n = 35 ) but was continued in the other two groups , and at 36 hours ipratropium was also stopped in group II ( n = 35 ) while patients in group III ( n = 36 ) continued with ipratropium for 60 hours . Spirometric tests were performed before and after salbutamol , and again 30 and 60 minutes after ipratropium or placebo at 12 , 36 and 60 hours . Peak flow rates ( PEFR ) were measured before and after each nebulisation . RESULTS There were no differences between the groups in PEFR on admission ( group I : 214 l/min , group II : 198 l/min , group III : 221 l/min ) , or mean forced expiratory volume in one second ( FEV1 ) at 12 hours ( group I : 1.8 l , group II : 2.0 l , group III : 2.2 l ) , 36 hours ( group I : 2.1 l , group II : 2.3 l , group III : 2.4 l ) , or at 60 hours ( group I : 2.2 l , group II : 2.3 l , group III 2.5 l ) . Despite this , median time to discharge was significantly higher for patients in group I ( 5.4 days ) than for those in groups II ( 4.1 days ) and III ( 4.0 days ) . CONCLUSIONS Combination nebulised therapy can be continued beyond 12 hours and up to 36 hours after admission with improved recovery time . Lung function testing may not reflect the full benefit of treatment In order to determine the duration of action of the inhaled anticholinergic agent oxitropium bromide , a controlled study of the effect of pre-treatment with oxitropium bromide 200 micrograms against cholinergic challenge was carried out in ten asthmatic subjects ( 6 children , 4 adults ) . After baseline measurements of lung function ( FEV1 and sGaw ) and methacholine PC20 ( the concentration of methacholine to produce a 20 % fall in FEV1 ) oxitropium bromide or placebo were inhaled double-blind on 2 separate days . Lung function and methacholine PC20 were then measured at 1 , 3 and 6 h post dosing . Oxitropium bromide caused significant protection from methacholine challenge for 6 h ( p less than 0.05 ) A multi-center , double-blind , 90-day study compared an ipratropium bromide metered-dose inhaler ( 40 microgram four times a day ) with a metaproterenol metered-dose inhaler ( 1,500 micrograms four times a day ) in 164 patients with asthma ; of the 144 patients who completed the study , 71 received ipratropium and 73 received metaproterenol . Our results suggest that both drugs were equally effective bronchodilators . Although the shape of the pulmonary function response curves suggested that ipratropium has different bronchodilator kinetics than metaproterenol ( in that it has a slower onset of action and a more prolonged duration ) , comparison of the areas under the curves for the two drugs showed that there was no statistical difference between ipratropium or metaproterenol . The only significant side effects noted with ipratropium were cough and exacerbation of symptoms ; no anticholinergic side effects were noted 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 Thirty seven children with acute asthma were given nebulised ipratropium or placebo 30 minutes after their first dose of salbutamol and eight hourly thereafter . There were no significant differences between the two groups in clinical scores , peak expiratory flow rates , length of stay in hospital , or the need for oral steroids Six asthmatic children were studied to determine whether supplemental , parenteral atropine would increase the effects of bronchodilation and protection against exercise-induced bronchoconstriction after maximal effects had been achieved by inhalation . First , we determined the amount of inhaled atropine sulfate that would give maximal bronchodilation for each patient at rest . This quantity of atropine was design ated as " A. " Then all subjects exercised for five sessions with the following pre-exercise treatments in a r and om order : ( a ) inhaled distilled water plus intramuscular ( IM ) saline solution ; ( b ) inhaled A dose of atropine plus IM saline solution ; ( c ) inhaled distilled water plus 0.35 mg IM atropine ; ( d ) inhaled A dose of atropine plus 0.35 mg IM atropine ; and ( e ) inhaled double the A dose plus IM saline solution . The results showed that the combination of inhaled and IM atropine had the greatest bronchodilation effect and the greatest protection against exercise-induced bronchoconstriction .  Atropine inhalation alone ( A dose ) or IM injection ( 0.35 mg ) was not as effective in bronchodilation or in alleviation of exercise-induced bronchoconstriction . Doubling the dose of inhalation ( 2A ) did not increase the effects of the A dose . These results support the hypothesis that inhaled atropine does not reach all the airways where cholinergic receptors are present Until now very few studies have been performed on the prevention of exercise-induced asthma ( EIA ) in children with ipratropium bromide + fenoterol .  This is why we decided to study 30 children aged between 6 and 15 years , whose EIA was confirmed by a test including a 6-min free race on day 1 of the study . The criterion was a decrease of more than 20 % of the basal values of forced expiratory volume in 1 s ( FEV1 ) or FMF .  Children whose FEV1 or FMF baseline values were under 60 % of those expected according to Polgard tables were excluded . Three tests were performed , the first to determine EIA , the second was performed 72 h later after inhalation of placebo . 72 h after day 2 the patients returned in order to repeat the test , but this time , aerosol therapy with the combination ipratropium + fenoterol was applied prior to the race . The dosage of the combination was 1 puff of aerosol per 10 kg body weight , up to a maximum of 4 puffs . Each puff of the combination contains 0.02 mg of ipratropium bromide and 0.05 mg fenoterol . Functional assessment of children was carried out by means of forced spirometry . There were no significant differences between the placebo group and the group which received no medication , but there was a significant difference between the treated group and the other two , not only in the FEV1 and FMF values but also in forced vital capacity TEST . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Glycopyrrolate , a quaternary ammonium anticholinergic compound is a potentially useful bronchodilator . To determine the efficacy , optimal dose , and duration of action of inhaled glycopyrrolate , we gave the drug to 11 asthmatic patients . Each subject received placebo or glycopyrrolate ( 100 , 200 , 600 , or 1,200 micrograms ) by inhalation in a double-blind , r and omized , crossover design . Measurements included FEV1 , FVC , heart rate , and blood pressure before administration of the drug and periodically for 12 hours . For eight hours following all doses of glycopyrrolate , both FEV1 and FVC ( both as percent of predicted ) were significantly greater for drug than for placebo . Glycopyrrolate may be a useful long-acting drug for the treatment of asthma Abstract We have examined the role of cholinergic reflex mechanisms in non-allergic bronchial hyperresponsiveness by examining the effect of pretreatment with ipratropium bromide ( a cholinergic antagonist ) and fenoterol ( a β 2 -adrenergic agonist ) on histamine- and methacholine-induced bronchoconstriction . Twelve adult asthmatics inhaled histamine acid phosphate and methacholine to determine the provocative concentration causing a fall in FEV 1 of 20 % ( PC 20 ) , after double-blind r and omized administration of ipratropium bromide ( 80 μg ) , fenoterol ( 800 μg ) or placebo . Ipratropium increased the mean PC 20 methacholine from 1.12 to 59.67 mg/ml ( P 20 increased from 1.17 to 1.93 mg/ml . This was not statistically significant after correction for any change in base-line FEV 1 . Fenoterol increased the mean PC 20 methacholine from 1.12 to 17.76 mg/ml ( P 20 histamine from 1.17 to 10.61 mg/ml ( P P = 0.001 ) . No such relationship was found with fenoterol and methacholine or with ipratropium and histamine or methacholine . Inhalation of high doses of methacholine appeared to induce late asthmatic responses in four subjects , similar to those observed after inhalation of allergen by sensitized subjects . We conclude that : 1 . 1.|Cholinergic reflex mechanisms are not important in histamine-induced bronchoconstriction or in the pathogenesis of non-allergic bronchial hyperresponsiveness . 2 . 2.|The degree of non-allergic hyperresponsiveness to histamine may be related to the severity of β-receptor dysfunction . 3 . 3.|High concentrations ( doses ) of methacholine may induce responses of the late asthmatic type STUDY OBJECTIVE To evaluate the effects of nebulized ipratropium bromide on intraocular pressures and pupillary responses in children with asthma . DESIGN A double-blind , r and omized , crossover study . SETTING Children 's Hospital of Winnipeg , University of Manitoba . PATIENTS OR PARTICIPANTS Age 6 to 17 years with asthma . INTERVENTION Nebulized ipratropium bromide added to albuterol sulfate , albuterol alone , or saline solution was given by face mask and nebulizer . Before and 0.5 h after nebulization , intraocular pressures ( mm Hg ) , pupillary size ( mm ) , and pupillary responses were measured . In a subsequent open study , patients who had been admitted to hospital with acute asthma who were treated with nebulized ipratropium bromide were recruited for measurement of intraocular pressures , pupillary size , and pupillary responses . MEASUREMENTS AND RESULTS Twenty patients completed the double-blind study , and 26 patients completed the open study . There were no changes in intraocular pressures , pupillary size , or pupillary response after any treatment on any study day in either the double-blind or the open studies . CONCLUSION In children with asthma , who have no pre-existing ocular abnormalities , the risk of an adverse reaction to nebulized ipratropium bromide delivered by face mask inadvertently absorbed in the eye is extremely small STUDY OBJECTIVE To determine the effect of adding the nebulized anticholinergic drug ipratropium bromide to st and ard therapy compared with st and ard therapy alone for acute severe asthma ( peak expiratory flow rate [ PEFR ] < 50 % of predicted ) in children presenting to the emergency department . METHODS Ninety children aged 6 to 18 years were r and omly assigned to two groups in a prospect i ve , double-blind , placebo-controlled study performed in the ED of an urban children 's hospital . All children received nebulized albuterol solution ( .15 mg/kg ) every 30 minutes , and all received oral steroids with the second dose of albuterol . Children in group 1 received ipratropium bromide ( 500 micrograms/dose ) with the first and third dose of albuterol those in group 2 received saline placebo instead of ipratropium .  Pulmonary functions ( PEFR and 1-second forced expiratory volume [ FEV1 ] ) and physiologic measurements were assessed every 30 minutes up to 120 minutes . By chance , the baseline values for percent of predicted PEFR and FEV1 differed between the two groups . Therefore a multivariate model accounting for both time and baseline effects was used to compare the response between groups . RESULTS On average , and adjusting for baseline measures , children in the ipratropium group had a significantly greater improvement in percent of predicted PEFR than did children in the placebo group at 60 minutes ( P = .02 ) , 90 minutes ( P = .002 ) , and 120 minutes ( P < .0001 ) . The improvement in percent predicted FEV1 was significantly greater for children in the ipratropium group only at 120 minutes ( P = .013 ) . Nine children ( 20 % ) from the ipratropium group and 14 ( 31.1 % ) from the control group were admitted ( P = .33 , chi 2 ) . There were no significant adverse effects attributable to the ipratropium , and there was no relation between ipratropium use and changes in pulse , respiratory rate , blood pressure , or oxygen saturation . CONCLUSION We detected significant improvement in pulmonary function studies over 120 minutes in children with severe asthma who were given nebulized ipratropium combined with albuterol and oral steroids , compared with children who received the st and ard therapy . Further study is needed to determine whether early use of ipratropium decreases the need for hospitalization BACKGROUND Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children . The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children . We studied the feasibility and effects of this therapy compared with placebo in children aged 1 - 4 years . METHODS 218 children aged 1 - 4 years with moderate asthma were recruited through 151 general practitioners between March , 1995 , and March , 1996 . They were r and omly assigned sodium cromoglycate ( 10 mg three times daily ) or placebo , given by inhaler with spacer device and face-mask for 5 months . Rescue medication ( ipratropium plus fenoterol aerosol ) was available during the baseline period of 1 month and the intervention period . Parents completed a daily symptom-score list . The primary outcome measure was the proportion of symptom-free days in months 2 to 5 . Analysis was by both intention to treat and on treatment . FINDINGS 167 ( 77 % ) children completed the trial . 131 ( 78 % ) of these children used at least 80 % of the recommended dose . Of the 51 children who stopped prematurely , 23 had difficulties with inhaled treatment . The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period ( 95 % CI for mean difference 5.1 to 17.5 cromoglycate , 11.9 to 23.3 placebo ) . However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days ( mean 65.7 [ SD 25.3 ] vs 64.3 [24.5]% ; 95 % CI for difference -8.46 to 5.70 ) or in any other outcome measure . INTERPRETATION Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years . However , long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group Although adenosine-induced bronchoconstriction is mainly due to mast cell mediator release , vagal reflexes have also been implicated in this response . We have investigated the effect of a specific muscarinic-receptor antagonist , ipratropium bromide , on methacholine- and adenosine-induced bronchoconstriction in a r and omized , placebo-controlled , double-blind study of 12 asthmatic subjects . Airway response was evaluated as forced expiratory volume in one second ( FEV1 ) . Inhaled ipratropium bromide ( 40 micrograms ) , administered 20 min prior to bronchoprovocation , increased the provocation dose of inhaled methacholine and adenosine required to reduce FEV1 by 20 % from baseline ( PD20 ) from 0.11 to 0.79 mg ( p less than 0.01 ) and from 0.57 to 1.27 mg ( p less than 0.01 ) , respectively . The mean baseline FEV1 values after administration of ipratropium bromide were significantly higher than after placebo administration ( p less than 0.05 ) . However , there was no correlation between the degree of bronchodilatation and dose-ratios for methacholine and adenosine . The findings of the present study implicate vagal reflexes in the bronchospastic response induced by inhaled adenosine in asthma A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma . A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide .  Twenty-five children ranging in age from 5 to 15 years were enrolled in the study . Children with FEV1 less than or equal to 55 % predicted were eligible to participate in the study . Subjects were r and omized in a double-blind fashion into one of two treatment groups . Both groups received an initial dose of salbutamol by nebulizer of 150 micrograms/kg ( 0.03 cc/kg ) , followed by six consecutive doses of 50 micrograms/kg ( 0.01 cc/kg ) at 20-minute intervals . In one group of subjects , 250 micrograms ( 1.0 ml ) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation , and at 40 and 80 minutes , whereas the remaining subjects received a placebo with salbutamol at those times . Formal one-way statistical ANOVA with change in percent predicted FEV1 as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period . There was no significant difference in side effects reported in the two groups . Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group The ability of atropine to inhibit exercise-induced bronchospasm was evaluated in 18 children with chronic , perennial asthma . In 17 of 18 patients , exercise-induced bronchospasm was blocked by prior inhalation of 0.1 mg per kg of atropine sulfate , administered in a r and omized single blind fashion . In 14 of these 17 patients , significant bronchodilatation occured after the combination of atropine and exercise . Placebo failed to inhibit exercise-induced bronchospasm in any patient . These results suggest that the parasympathetic nervous system has a role in the mediation of exercise-induced bronchospasm in children We studied the effects of the anticholinergic ipratropium bromide ( 40 micrograms three times daily ) and the beta-agonist , fenoterol ( 0.2 mg three times daily ) , both administered by powder inhaler , on bronchial hyperresponsiveness ( BHR ) to histamine in children , aged 7 to 15 years with mild stable asthma and limited bronchoconstriction who had a highly increased BHR .  The double-blind , r and omized , parallel study was conducted and performed in spring and early summer . BHR and FEV1 were measured on two occasions , before the start of treatment and monthly thereafter for 4 months . Symptoms , peak expiratory flow , and concomitant medication were registered daily . Nine of the 12 patients receiving ipratropium bromide and all eight patients receiving fenoterol  completed the study . Patients completing treatment had few symptoms and were in a stable condition throughout the treatment period . Neither the administration of ipratropium bromide nor fenoterol result ed in a significant change of BHR . We concluded that long-term treatment with ipratropium bromide or fenoterol had no effect on BHR in children with mild stable asthma Ipratropium ( 40 micrograms ) and theophylline ( oxtriphylline 400 mg ) were administered to 24 asthmatics in a r and omized double-blind placebo controlled trial . The combination of these agents produced additive bronchodilation for up to two hours , with a 23 percent maximal increase in FEV1 . This regimen promises to be safe , effective therapy for patients with asthma Thirty one children with asthma were given 40 micrograms of ipratropium bromide and identical placebo by inhalation three times a day in a double blind , r and omised crossover study to test the ability of an anticholinergic drug to modify the diurnal variation in airway calibre and bronchial reactivity . Subjects measured peak expiratory flow rate approximately eight hourly , before and after inhaled salbutamol , for four week periods . Paired t tests and cosinor analysis were used to assess the diurnal variation in airway calibre from the peak expiratory flow rate recorded before salbutamol and to assess the diurnal variation in bronchodilator responsiveness from the increase in peak expiratory flow rate after salbutamol . Maintenance treatment with ipratropium bromide 40 micrograms three times daily reduced the provocative dose of histamine which caused a 20 % fall in FEV1 ( geometric mean PD20 = 0.78 v 0.49 mg/ml , p less than 0.05 ) , despite an eight to 12 hour gap between the last dose of ipratropium and histamine challenge . It did not , however , diminish the diurnal variation in airway calibre ( mean amplitude = 12.7 v 10.1 ) or in bronchodilator responsiveness ( mean amplitude = 62.4 v 63.5 ) . There was no improvement in the clinical state of subjects while they were taking ipratropium bromide The new anticholinergic compound Sch 1000 ( ipratropium bromide ) has been reported to be an effective bronchodilator without significant atropine-like side effects . We evaluated the effectiveness of different doses of nebulized Sch 1000 ( 40 microgram and 80 microgram ) aerosolized atropine sulfate ( 1 mg ) and placebo in the prevention of exercise-induced bronchospasm ( EIB ) in 20 children with atopic bronchial asthma . A r and om , crossover double-blind protocol was used . St and ard exercise on a cycloergometer was used to induce EIB . Pulmonary function was determined before and after drug administration and exercise . Following no treatment or placebo , exercise result ed in average reductions of 33 % to 43 % in plethysmographic specific airway conductance ( SGaw ) , of 20 % to 25 % in forced expiratory volume in 1 sec ( FEV1 ) , and of 25 % to 32 % in maximal midexpiratory flow rate . Exercise following no treatment or placebo result ed in average increases of 23 % to 30 % in thoracic gas volume ( Vtg ) . Prior to exercise atropine and either dose of Sch 1000 caused significant increases in SGaw ( 48 % to 59 % ) . After pretreatment with Sch 1000 or atropine , exercise caused SGaw to fall to values that were not significantly different from pretreatment medication values , but were significantly higher than values following exercise without pretreatment or after pretreatment with placebo . No significant differences were noted between the effects of atropine and Sch 1000 on EIB . We conclude that at the doses used atropine and Sch 1000 cause equivalent degrees of bronchodilation but neither drug specifically inhibits EIB 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 Isocapnic hyperventilation dose response curves were constructed for 11 asthmatic children before and after pretreatment with placebo or ipratropium bromide , 40 - 1500 micrograms given by inhalation , on three separate days . The response before and after placebo was highly reproducible ( within subject coefficient of variation 7.5 % , 18 % , and 22 % for intervals of two hours , within two weeks , and over two weeks ) . It was independent of baseline lung function . Complete protection against hyperventilation induced asthma was achieved by ipratropium bromide 40 micrograms in six children and by 200 micrograms or more in a further four . The remaining child was unaffected by any dose of ipratropium up to 1500 micrograms . The dose of ipratropium required for protection was better related to the subjects ' requirement for regular medication than to their sensitivity to hyperventilation or baseline lung function 16 hyperreactive asthmatics were challenged with an ultrasonic mist of H2O at the same time of day on 4 usually consecutive days 2 h after premedication with placebo , fenoterol ( 200 micrograms ) , ipratropium bromide ( 80 micrograms ) and Duovent ( fenoterol 200 micrograms + ipratropium bromide 80 micrograms ) , given in r and om order and double-blind conditions . The challenge test consisted of 3 exposures of 30 , 60 and 120 s with 4-min intervals . Specific airway resistance ( sRaw ) was measured under basal conditions and 1 , 2 and 3 min after each exposure . FEV1 was measured under basal conditions and immediately after the last sRaw measurement . Fenoterol afforded a good protection ; ipratropium bromide alone was ineffective but enhanced the protective effect of fenoterol when the two drugs were given in combination ( Duovent ) . A similar effect was also observed after a second challenge performed 1 h ( 9 patients ) or 3 h ( 6 patients ) after the first one , which was performed 2 h after premedication Twenty-four consecutive patients admitted to hospital with severe acute asthma were studied . Eleven were given 10 mg salbutamol by nebulizer followed 2 hours later by 500 micrograms of nebulized ipratropium bromide . These patients had a greater response in PEFR than 13 patients given two doses of 10 mg salbutamol 2 hours apart Ipratropium bromide was given to patients admitted to hospital with acute asthma . A cumulative-dose-response technique in six patients showed that 500 micrograms given by nebuliser produced a maximal increase in peak expiratory flow rate . This dose of ipratropium bromide was included in a regimen in which it was given either two hours before or two hours after nebulised salbutamol to 22 patients .  Ipratropium bromide given on admission was as effective as nebulised salbutamol . The two drugs in sequence produced greater bronchodilatation than either used alone , and the mean peak expiratory flow rate rose by 96 % in four hours . Thus giving ipratropium bromide in addition to salbutamol in severe asthma enhances the bronchodilator effect . Further studies are needed to determine whether the same effect may be obtained by giving two maximal doses of salbutamol two hours apart We studied the effect of ipratropium on  exercise-induced bronchoconstriction ( EIB ) at cold or warm temperatures . Although pulmonary function was better with ipratropium , its benefit was related to pre-exercise bronchodilation and not prevention of EIB .  Ipratropium did not affect the augmented EIB in cold weather . Therefore , these phenomena are not primarily mediated via cholinergic mechanisms Varying doses of nebulized salbutamol , ipratropium bromide and a combination of both were given to 20 asthmatic children . All therapies produced effective bronchodilation . Ten mg salbutamol caused elevation of pulse rate and finger tremor whilst the duration of action of 0.6 mg salbutamol was too short . Dose-response effects were clearly seen with salbutamol but not with ipratropium bromide . A summation effect was not demonstrated when the medications were combined Fifteen children with exercise-induced asthma ( EIA ) participated in a double-blind trial comparing the protective effects of inhaled sodium cromoglycate ( 20 mg/2ml ) , ipratropium bromide ( 500 μg/2ml ) and verapamil ( 5 mg/2ml ) . Saline was used as control . There was no significant difference in base line pulmonary function before and after the administration of each agent . After exercise the maximal percentage fall in the forced expiratory volume in 1 s ( FEV-1 ) ( means and SD ) were 40.9±17.2 after inhalation of saline , 15.3±11.7 after sodium cromoglycate , 36.2±21.4 after verapamil and 21.7±17.7 after ipratropium bromide . The inhibitory effects of sodium cromoglycate and ipratropium  bromide were significant whereas verapamil failed to produce any effect . To see if a double dose of verapamil is more effective , nine different children with EIA were provoked by the same st and ardized treadmill running after giving a placebo ( 4 ml saline ) and after verapamil ( 10 mg in 4 ml ) . Despite the double dose , again verapamil was ineffective even though the protection index doubled that obtained with the lower dose . The results suggest that the calcium antagonist ( verapamil ) had almost no effect on the prevention of EIA in the children studied Atropine is known to be an effective bonrchodilator . We studied the effectiveness of aerosol Sch 1000 , a derivative of atropine , in relieving bronchoconstriction in asthma . A single dose of drug was effective within 5 min , and the effect had a duration of 4 hours . No side effects were noted . The major effect of the drug appeared to be in large airways Objective . To determine if the addition of ipratropium bromide to the emergency department ( ED ) treatment of childhood asthma reduces time to discharge , number of nebulizer treatments before discharge , and the rate of hospitalization . Methods . Patients > 12 months of age were eligible if they were to be treated according to a st and ardized ED protocol for acute asthma with nebulized albuterol ( 2.5 mg/dose if weight < 30 kg , otherwise 5 mg/dose ) and oral prednisone or prednisolone ( 2 mg/kg up to 80 mg ) . Subjects were r and omized to receive either ipratropium ( 250 μg/dose ) or normal saline ( 1 mL/dose ) with each of the first three nebulized albuterol doses . Further treatment after the first hour was determined by physicians blinded to subject group assignment . Records were review ed to determine the length of time to discharge home from the ED , number of doses of albuterol given before discharge , and the number of patients admitted to the hospital . Results . Four hundred twenty-seven patients were r and omized to ipratropium or control groups ; these groups were similar in all baseline measures . Among patients discharged from the ED , ipratropium group subjects had 13 % shorter treatment time ( mean , 185 minutes , vs control , 213 minutes ) and fewer total albuterol doses ( median , three , vs control , four ) . Admission rates did not differ significantly ( 18 % , vs control , 22 % ) . Conclusions . The addition of three doses of ipratropium to an ED treatment protocol for acute asthma was associated with reductions in duration and amount of treatment before discharge Seventeen hospitalized children with acute asthma , ages 7 to 15 years , were studied to determine the efficacy of simultaneous administration of atropine sulfate and isoetharine . Combination therapy was superior in 11/17 ( 65 % ) patients while isoetharine alone was superior in 4/17 ( 23 % ) patients ( P = .037 ) . We conclude that simultaneous administration of combination therapy is safe and beneficial in some children with acute asthma In thirteen patients with extrinsic asthma the effects of placebo , sodium cromoglycate , ipratropium bromide , and ipratropium bromide plus sodium cromoglycate were studied in a r and om double-blind fashion to assess their inhibitory action in exercise-induced asthma ( EIA ) . Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes . In eight of the 13 patients studied the baseline ratio of expiratory flow at 50 % vital capacity ( VC ) breathing helium-oxygen ( V50He ) to V50air was over 1.20 and they were called responders ; the remaining five patients were called non-responders . There was a significantly lower baseline maximum mid-expiratory flow rate ( MMEF ) in non-responders ( P less than 0.02 ) as compared to responders but no difference in forced expiratory volume in one second ( FEV1 ) or forced vital capacity ( FVC ) .  Sodium cromoglycate ( P less than 0.02 ) , ipratropium bromide ( P less than 0.01 ) , and ipratropium bromide plus spdium cromoglycate ( P less than 0.01 ) all significantly inhibited the percentage fall in FEV1 after exercise in the responders . Ipratropium bromide had no preventive action on non-responders , unlike sodium cromoglycate ( P less than 0.05 ) and ipratropium bromide plus sodium cromoglycate ( P less than 0.02 ) . It is postulated that mediator release is an important factor in development of EIA in most extrinsic asthmatics , whereas cholinergic mechanisms are relevant only in those patients in whom the main site of airflow obstruction is in the large central airways Treatment with nebulised salbutamol or a mixture of salbutamol and ipratropium was given to 138 children .  Length of hospital stay and number of nebulised doses required did not differ . In severe asthma response was greater with salbutamol alone . In mild asthma response was greater with combined treatment OBJECTIVES To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol , inhaled ipratropium , and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously . STUDY DESIGN R and omised , double blind , placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol .  RESULTS The placebo and treatment groups of children were similar at baseline . The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours . Five subjects in the placebo group were intubated and ventilated after enrolment compared with none in the aminophylline group . CONCLUSIONS Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment In two groups of patients , 15 with asthma and 15 with chronic bronchitis , the bronchodilator effects of ipratropium bromide , of fenoterol plus theophylline , and of the combination of the three drugs , were compared using a double-blind , single-dose , placebo-controlled format . Ipratropium bromide caused rapid bronchodilatation which was not significantly different in asthmatic patients and patients with bronchitis ( delta FEV1 = .29 L in one hour in asthmatic patients , .18 L in patients with bronchitis ) . In contrast , fenoterol plus theophylline induced a considerably greater effect in asthmatic patients ( delta FEV1 = .41 L in one hour ) than in those with bronchitis ( delta FEV1 = .07 in one hour ) . The use of the three drugs in combination compared with ipratropium bromide alone , or fenoterol plus theophylline alone , result ed in a significant additional bronchodilatation in asthmatic patients . In the patients with bronchitis , the triple combination was clearly superior to fenoterol plus theophylline . A similar trend was present in comparing the triple combination to ipratropium bromide , but the difference did not reach statistical significance . There was no evidence of synergism when ipratropium bromide was combined with fenoterol plus theophylline in that the total bronchodilator effect was approximately additive . Asthmatic patients and the physician were able to distinguish the triple combination from placebo . No such ability was demonstrated with respect to those with bronchitis . All three drugs were well tolerated . Side effects were mostly mild , and none was related to the use of ipratropium Inhaled bronchodilator therapy in young asthmatic children reduces symptoms and improves lung function . After a single dose of therapy , however , lung function may still be abnormal , as evidence d by an elevated function residual capacity ( FRC ) . The aims of this study were to assess if a second dose of bronchodilator therapy result ed in further improvement in lung function and to determine whether additional therapy was more effective if given as a second dose of a beta-adrenergic agonist or if instead an anticholinergic was used . Twenty-one asthmatics ( median age 7.5 years ) received in r and om order on two separate occasions , 1 week apart , either two doses of terbutaline ( 500 micrograms ) or terbutaline plus ipratropium bromide ( 20 micrograms ) . FRC and peak expiratory flow rate ( PEFR ) were measured immediately prior to and then 20 min after each dose of bronchodilator therapy . In the group , overall FRC and PEFR improved after the first and second dose of bronchodilator , regardless of regime used , the response to the second dose , however , was smaller than the first dose . There was no significant difference overall between the two regimes in baseline FRC or PEFR , or FRC and PEFR measured after each dose of bronchodilator . Eight children failed to show a significant change in FRC following two doses of terbutaline , but seven of these eight did have a significant change in FRC in response to the combination of terbutaline and ipratropium bromide . We conclude that a second dose of bronchodilator therapy does further improve lung function . Our results suggest the more efficacious regime consists of a combination of single doses of ipratropium bromide and terbutaline Beta 2-adrenergic and anticholinergic drugs have shown an action in modulating bronchial hyperreactivity  to various stimuli ( chemical , physical , immunological , pharmacological ) . The aim of our study was to compare the efficacy of a combination of ipratropium bromide and fenoterol ( Duovent ) with the activity of single drugs in the prevention of histamine-induced bronchospasm .  Twenty-six atopic asthmatic subjects were examined in a double-blind trial , during an asymptomatic period , with a FEV1 value not lower than 20 % of the predicted normal value . During 4 consecutive days all patients received 2 puffs , respectively , of Duovent ( 200 micrograms fenoterol + 40 micrograms ipratropium bromide ) , fenoterol ( 400 micrograms ) , ipratropium bromide ( 80 micrograms ) and placebo in a r and omized order . PD20 values were evaluated after each drug administration : after 2 h in 16 patients and after 5 h in the other 10 patients . The data were modified to log values , and statistical analysis was performed by two-way analysis of variance . This study showed that Duovent and fenoterol have a protective effect against histamine-induced bronchospasm with a significant increase in the PD20 values 2 h ( p less than 0.01 ) and 5 h ( p less than 0.05 ) after treatment when compared to placebo . Duovent inhalation determined a more protective effect than other drugs but not significantly when compared to fenoterol . Some advantages in the modulation of bronchial reactivity could be seen from using Duovent because with the lower dose of the beta 2-adrenergic drug the same results could be obtained without side-effects In a r and omized , double-blind , parallel-group trial , 47 children with acute asthma received a combination of ipratropium bromide solution ( 250 micrograms ) and fenoterol hydrobromide solution ( 625 micrograms ) , fenoterol solution ( 625 micrograms ) alone , or ipratropium solution ( 250 micrograms ) alone , administered by face mask and nebulizer , with the dose repeated 60 minutes later . The groups did not differ significantly with regard to age , pulmonary function at baseline , or any other variable . They were monitored at 30 , 60 , 90 , and 120 minutes by use of a clinical score , oxygen saturation , and pulmonary function tests . At the end of the study , albuterol was administered to assess residual bronchoconstriction . Clinical scores improved significantly after treatment in all groups at all times compared with baseline . The greatest improvement in FEV1 was seen in the patients treated with ipratropium/fenoterol , whether considered as absolute change , change in percent predicted , or percent change from baseline .  Ipratropium/fenoterol  was significantly better than fenoterol alone only when considered as percent change from baseline . Improvement in flow at mid and low lung volumes was significantly greater for the  ipratropium/fenoterol combination than for  ipratropium alone ; no significant differences were noted between ipratropium/fenoterol and fenoterol for flow at mid and low lung volumes . Treatment with albuterol did not significantly improve pulmonary function in the groups receiving ipratropium/fenoterol or fenoterol alone , but it did increase flow at all lung volumes in the group receiving ipratropium alone . No patient complained spontaneously of any adverse reactions , and no clinical ly significant changes in heart rate or systolic or diastolic blood pressures occurred . ( ABSTRACT TRUNCATED AT 250 WORDS To evaluate the role of the parasympathetic nervous system in the mediation and maintenance of reversible airway obstruction in perennially asthmatic children , we measured pulmonary function in 18 patients before and after the administration of atropine sulfate aerosol .  The bronchodilatory effects of atropine were compared with those of isoproterenol hydrochloride and placebo aerosols . Placebo aerosol did not change any of the pulmonary functions tested . Atropine and isoproterenol aerosols improved forced expiratory flows , airway resistance , and specific airway conductance significantly and to the same degree . Hyperinflation was significantly lessened by atropine , but not by isoproterenol . Because atropine is not a direct smooth muscle relaxant , but rather a selective blocker of cholinergically induced smooth muscle tone , any significant improvement in the lung function of chronically asthmatic children by atropine suggests that at least some of their reversible airway obstruction is induced and maintained by parasympathetically mediated bronchial smooth muscle constriction OBJECTIVE To determine whether the addition of repeated doses of nebulized ipratropium bromide ( IB ) to a st and ardized inpatient asthma care algorithm ( ACA ) for children with status asthmaticus improves clinical outcome . STUDY DESIGN Children with acute asthma ( N = 210 ) age 1 to 18 years admitted to the ACA were assigned to the intervention or placebo group in r and omized double-blind fashion . Both groups received nebulized albuterol , systemic corticosteroids , and oxygen according to the ACA . The intervention group received 250 microg IB combined with 2.5 mg albuterol by jet nebulization in a dosing schedule determined by the ACA phase . The placebo group received isotonic saline solution substituted for IB . Progression through each ACA phase occurred based on assessment s of oxygenation , air exchange , wheezing , accessory muscle use , and respiratory rate performed at prescribed intervals . RESULTS No significant differences were observed between treatment groups in hospital length of stay ( P = .46 ) , asthma carepath progression ( P = .37 ) , requirement for additional therapy , or adverse effects .  Children > 6 years ( N = 70 ) treated with IB had shorter mean hospital length of stay ( P = .03 ) and more rapid mean asthma carepath progression ( P = .02 ) than children in the placebo group . However , after adjustment was done for baseline group differences , the observed benefit of IB therapy in older children no longer reached statistical significance . CONCLUSION The routine addition of repeated doses of nebulized IB to a st and ardized regimen of systemic corticosteroids and frequently administered beta-2 agonists confers no significant enhancement of clinical outcome for the treatment of hospitalized children with status asthmaticus The bronchodilator activity in nebulised salbutamol , ipratropium bromide , clemastine , and a placebo was studied in 14 asthmatic children aged between 3 and 5 years . Changes in lung function were monitored by measuring peak expiratory flow rate and total respiratory resistance using a modification of the forced oscillation technique . Ipratropium bromide produced a degree of bronchodilation similar to that of salbutamol , but the bronchodilatory activity of clemastine was not appreciably better than for the placebo The effects of nebulized solutions of ipratropium bromide and fenoterol combined were compared with the response to either preparation alone in single dose and longer-term administration in children who had asthma . The combination produced a slightly greater response than either alone , especially in peak expiratory flow . Over a 1-month period , there were no significant differences in symptom scores or lung function parameters between the combination of ipratropium bromide and fenoterol and fenoterol alone in a group of children who had asthma . It is possible that the addition of ipratropium bromide to a sympathomimetic drug may be useful in a subgroup of asthmatics , particularly if there is a considerable large airway contribution to bronchial narrowing STUDY OBJECTIVES To assess the safety and efficacy of salmeterol xinafoate as an adjunct to conventional therapy for the in-hospital management of acute asthma . DESIGN A prospect i ve , double-blind , r and omized placebo-controlled trial . SETTING Medical wards of a large university-based hospital . PATIENTS Forty-three patients admitted for an acute exacerbation of asthma . INTERVENTIONS Salmeterol ( 42 microg ) or two puffs of placebo every 12 h in addition to st and ard therapy ( short-acting beta-agonists , corticosteroids , and anticholinergic agents ) . RESULTS No clinical ly adverse effects were seen with the addition of salmeterol to conventional therapy . After salmeterol , there was no difference in pulse , respiratory rate , oxygen saturation by pulse oximetry , severity of symptoms , or dyspnea score . Patients receiving salmeterol had greater FEV(1 ) percent improvements than the placebo group at 12 , 24 , 36 , and 48 h. These findings were not statistically significant . By paired Student 's t tests , there were significant improvements in FEV(1 ) ( p = 0.03 ) and FVC ( p = 0.03 ) in the salmeterol group after 48 h of treatment with no comparable improvement in the placebo group . In a subgroup analysis of patients with an initial FEV(1 ) < or = 1.5 L , the absolute FEV(1 ) percent improvement for salmeterol vs placebo was 51 % vs 16 % at 24 h and 54 % vs 40 % at 48 h. The relative FEV(1 ) percent improvement for salmeterol vs placebo was 17 % vs 8 % at 24 h and 18 % vs 14 % at 48 h. CONCLUSION The addition of salmeterol to conventional therapy is safe and may benefit hospitalized patients with asthma . Further studies are needed to clarify its role in the treatment of acute exacerbation of asthma In a r and omized , double-blind , placebo-controlled study , we investigated the protective effects of ipratropium bromide 160 micrograms and 320 micrograms and terbutaline 500 micrograms on ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction in nine stable asthmatic patients . Both drugs caused a significant increase ( P < 0.001 ) in baseline FEV1 with no significant differences between the drugs or both doses of ipratropium bromide . Pre-inhalation of ipratropium bromide 320 micrograms and terbutaline 500 micrograms inhibited UNDW-induced bronchoconstriction ( P < 0.01 ) , whereas ipratropium bromide 160 micrograms had no protective effect . The protective effects of ipratropium bromide showed a large interindividual variation . There was no correlation between the increase in baseline FEV1 and PD20 UNDW , indicating that the protective effect on UNDW-induced bronchoconstriction is not dependent on the bronchodilation induced by terbutaline and ipratropium bromide . It also appears that the UNDW-induced bronchoconstriction is at least partly vagally mediated The role of the anticholinergic drug , ipratropium bromide , in maintenance antiasthmatic therapy was evaluated in a double-blind crossover trial of three bronchodilator regimens : ( 1 ) inhaled ipratropium , placebo , and oral oxtriphylline ; ( 2 ) inhaled fenoterol , placebo , and oral oxtriphylline ; and ( 3 ) both inhaled ipratropium and fenoterol plus oral oxtriphylline .  Twenty-two asthmatics were treated with all three regimens , each for 1 mo , allocated in r and om sequence . On the first and last treatment days of each month , spirometric measurements were performed before and 0.5 , 1 , 2 , 3 , 4 , and 6 hr after administration of the test drugs . On the first treatment day of each month , all regimens produced significant bronchodilatation at 30 min after dose , an improvement that declined between 3 and 6 hr after dose . After continuous administration for 1 mo the two combinations employing fenoterol showed a decline in bronchodilator responsiveness from the initial treatment day , measured as the level of response ( V50 ) or duration of response ( FEV1 , VC ) . Ipratropium plus oxtriphylline showed no such decline , suggesting the development of tolerance to long-term administration of fenoterol . Overall benefit at the end of 1 mo , measured as the area under the curves of FEV1 , VC , or V50 vs time after dose , was greatest for the triple drug regimen . There were no differences in heart rate , blood pressure response , or side effects among the three treatments . It is concluded that when the anticholinergic drug ipratropium is administered concurrently with an inhaled beta 2 agonist and an oral theophylline derivative , increased bronchodilatation occurs with no detectable additional side effects OBJECTIVES To compare the effectiveness and safety of alternative nebulized drug protocol s in children with mild or moderate asthma exacerbations . METHODS We conducted a blinded , r and omized , controlled trial with a 2 x 2 factorial design . Two interventions , nebulized salbutamol in frequent low doses ( 0.075 mg/kg every 30 minutes ) and the addition of ipratropium bromide ( 250 micrograms ) , were compared with salbutamol in hourly high doses ( 0.15 mg/kg every 60 minutes ) in children with mild or moderate acute asthma . The primary end point was the improvement in respiratory resistance . Secondary end points included oxygen saturation , corticosteroid use , patient disposition , and relapse status . RESULTS A total of 298 participants aged 3 to 17 years were studied , and 15 % were admitted to the hospital ; 14 % of the children had  relapses . No increased bronchodilation was associated with frequent low doses versus hourly high doses of salbutamol ( RR = 0.9 [ 95 % confidence interval 0.7 , 1.3 ] ) or the addition of ipratropium bromide versus placebo ( RR = 1.0 [ 0.8 , 1.3 ] ) . No group differences were observed in secondary end points . Salbutamol in frequent low doses was associated with increased vomiting ( RR = 2.5 [ 1.1 , 6.0 ] ) . CONCLUSION Our results do not support the use of frequent low doses of nebulized salbutamol or the addition of ipratropium bromide compared with hourly high doses of salbutamol in children with mild or moderate asthma OBJECTIVE The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma . METHODS One hundred twenty children ( 5 to 17 years ) of age ) with severe acute asthma ( forced expiratory volume in 1 second ( FEV1 ) , < 50 % of the predicted value ) were enrolled into a r and omized double-blind three-arm placebo-controlled trial comparing three groups : group 1 , three doses of nebulized ipratropium bromide within 60 minutes ( 250 micrograms/dose ) ; group 2 , one dose of ipratropium ; group 3 , no ipratropium . All patients were also treated with three doses of nebulized albuterol within 60 minutes ( 0.15 mg/kg per dose ) . Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes . RESULTS The groups were comparable at baseline . At 120 minutes , the mean percentage of predicted FEV1 improved from 33.4 % to 56.7 % in group 1 , from 34.2 % to 52.3 % in group 2 , and from 35.4 % to 48.4 % in group 3 ( p = 0.0001 ) . The differences between groups were larger in those children with a baseline FEV1 < or = 30 % of the predicted value : FEV1 increased from 24.5 % to 50.9 % in group 1 , from 25.0 % to 39.8 % in group 2 , and from 25.9 % to 36.5 % in group 3 ( p = 0.0001 ) . In group 1 , 38 % of the patients were hospitalized after the study , 44 % in group 2 , and 46 % in group 3 ( p value not significant ) . However , in patients with FEV1 < or = 30 % , the hospitalization rates were 27 % in group 1 , 56 % in group 2 , and 83 % in group 3 ( p = 0.027 ) . There were no toxic effects attributable to ipratropium . CONCLUSION The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone ; its use in patients with very severe asthma may reduce hospitalizations We examined the resolution of the  bronchial spasm  induced by methacholine after administration of a dose sufficient to provoke PD20 to study , in patients with bronchial asthma , how spontaneous resolution ( as opposed to bronchodilator-induced resolution ) takes place . According to a r and omization criterion , the patients were divided into four groups : 1 ) resolution induced by salbutamol ( S ) , 2 ) by ipratropium bromide ( I ) , 3 ) after placebo ( P ) and 4 ) spontaneous resolution ( R ) . In brief , we observed that variations in FEV1 after methacholine PD20 , reach statistically significant levels after 15 minutes in patients from groups ( S ) and ( I ) , after 30 minutes in patients from groups ( P ) and ( R ) ( p < 0.05 ) . Comparing the phenomenon at various intervals in the four experimental situation , we found a pairing trend : groups ( S ) and ( I ) on the one h and , and groups ( P ) and ( R ) on the other . On the whole , this phenomenon shows that pharmacological treatment accelerates the process of spontaneous resolution of the bronchial spasm induced by methacholine which , in our experience , beings to show after 15 minutes , and that after 60 minutes , there are no statistically significant differences in the four groups . It is our opinion that closer examination of this phenomenon may provide greater knowledge of the mechanisms that come into play during the phase after stimulation of the muscarinic receptors and that reasonably involve the system to eliminate the muscarinic drug The efficacy and acceptability of ipratropium given by metered-dose inhaler were evaluated in two double-blind crossover tests against placebo , one preceding and one following a 2-wk period of continual open-label ipratropium treatment . Ten patients with chronic bronchitis and 10 with bronchial asthma participated .  Ipratropium produced increase in FEV 1 of more than 15 % within 5 min of inhalation , and this effect was maintained for 4 to 5 hr . Statistically significant mean increases over the FEV 1 baseline values were recorded after ipratropium treatment in both the initial and the final crossover tests . There were no adverse reactions to any of the placebo or ipratropium test doses or to the ipratropium treatment . Serial electrocardiograms , laboratory tests , blood pressure , and pulse rate showed no change from lthe baseline . Sputum volume and dry-weight determinations in the patients with bronchitis before and after the 14-day treatment revealed no changes Ulrik CS , Backer V , Bach‐Mortensen N. Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma 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 Inhaled albuterol ( A ) ( salbutamol ) alone and albuterol plus ipratropium bromide ( IB ) were administered to 12 asthmatic children . Following administration of A alone or in combination with IB , there was a significant increase in FEV1 and FEF . Significant statistical difference in favor of the association A plus IB was observed at 120 and 240 minutes for FEV1 and in the period 120 , 180 , and 240 minutes for FEF . The additive effect was present both in the large and small airways . The short-lived additive effect of A plus IB suggests the opportunity to increase the frequency of drug administration in patients with severe bronchial obstruction n the 1960 's . Boehringer-Ingelheim , Ltd synthesized a 1 . s e n e of atropine derivatives , including N isopm pylnortropine tropic acid ester methyl bromide ( Atru vent ) . This drug is class8ed pharmacologically as an anticholinergic and its mechanism of action is vagal inhibition which prevents reflex bronchoconstriction . When given parenterafly , it bas anticbolinergic activity equal to or more potent than atropine . However , when administered by inhalation as a metered aerosol low doses are effective in the bronchial @ee ( local effect ) and do not show any atropine-like side effects . It may therefore be characterized as a peripheral anticholinergic , exercising particularly high spasmolytic activity in the bronchial region . The portion of Atrovent which adheres to the oral and pharyngeal mucosa and is later & lowed is poorly absorbed and therefore does not produce atropine-like effects even after high doses . Because of i b lack of cardiac effects Atrovent may be considered as a therapeutic alternative to beta-adrenergic bmnchodilators , especially for patients who are particularly sensitive to sympatbomimetic stimulation . Thirteen patients with asthma , as defined by the American Thoracic Society , were studied during a stable period of their disease . There were six males and seven females ranging in age from 18 to 52 yean ( mean 25 yean ) wbose asthma varied from miM to severe .  Reversible bronchospasm was confirmed at the enby into the study by demonstrating an improvement of at least 15 percent increase in FEV , . within 30 minutes fouowing two inhalations of isoproterend from a metered dose inhaler . Isoproterenol ( 0.15 mg ) was used as a control in a double-blind comparison with Atrovent ( 0.40 mg ) administered at one dosage level , so that each patient received a total of two beatments with an interval of at least 24 hours between treatments . The sequence of treatments was r and omized The bronchodilator effect of nebulized AMN , albuterol and their combination was evaluated in 16 steroid-dependent asthmatic children . In phase 1 , maximal bronchodilation was determined by dose-response studies on separate days . Maximal bronchodilator dose of each drug was administered either alone or in combination during phase 2 . In phase 1 , 0.11 + /- 0.01 mg/kg of albuterol and 0.03 mg/kg of AMN produced maximum bronchodilation . In phase 2 , the peak response to albuterol occurred within 30 min and to AMN , at 60 min . Maximal FEV1 achieved after AMN was 90 percent of the maximal achieved after albuterol . AMN FEV1 response was better than for placebo for 3 h ; that for albuterol was better for 4 h. Combination therapy produced a peak response similar to that of albuterol but was better than albuterol by 6 h. Thus , the maximum bronchodilator effect of AMN is less than that of albuterol in asthmatic children , but the combination may extend the period of bronchodilatation Thirteen children with perennial bronchial asthma , with a mean age of 11.2 years , were studied concerning the bronchodilatory effect of ipratropium bromide in cumulative doses . All the children had reduced basal forced expiratory flow ( FEV1 ) and bronchial reversibility of at least 20 % after inhalation of salbutamol . The study had a double-blind design with a crossover technique . The inhaled dose of ipratropium bromide solution was increased stepwise from 25 micrograms to 500 micrograms and saline was used as the placebo .  FEV1 was recorded 20 , 40 , and 60 minutes after inhalation of the test solution . At the lower ipratropium bromide dose levels no bronchodilatory effect was seen , but 60 minutes after the inhalation of 500 micrograms ipratropium bromide the increase in the FEV1 was significantly greater than that after placebo . Additional inhalation of salbutamol caused no further rise in FEV1 . At the 500-micrograms level a fall in the heart rate was noted . No side effects occurred . We concluded that ipratropium bromide has bronchodilatory properties in childhood asthma when given in sufficiently high doses Eleven patients with bronchial asthma and 10 with chronic bronchitis were treated over four consecutive 3-day periods , firstly with aerosols either of ipratropium bromide ( 40 microgram four times a day ) or of salbutamol ( 200 microgram four times daily ) by r and om allocation , then the alternate drug , next by both drugs together , and finally with prednisolone ( 10 mg three times daily ) in addition to both drugs . The effects of these four treatment periods were assessed both clinical ly and by measuring ventilatory capacity , nitrogen slope and progressive exercise testing . Ipratropium bromide and salbutamol produced approximately equal improvements in both diseases , with salbutamol showing a marginal advantage in patients with asthma . The combination of both drugs together more than doubled the FEV1 change in both groups of patients . The addition of prednisolone to both drugs produced a marginal advantage only in those with asthma Oxatomide is a potent inhibitor of both the release and effects of allergic mediators and is similar to calcium antagonists in chemical structure . It prevents histamine release by inhibiting not only the increase in calcium intake , but also intracellular calcium release . We investigated its effect on methacholine-induced and exercise-induced bronchoconstriction in asthmatic children .  Methacholine challenges were performed after oral administration of 0.88 mg/kg oxatomide or placebo in nine asthmatic children in a double-blind placebo-controlled study . Respiratory thresholds were improved in seven patients and log PC20 in the oxatomide group ( 6.65 + /- 1.34 micrograms/mL ) was significantly higher than that in the placebo group ( 5.74 + /- 1.04 micrograms/mL ) ( P < .05 ) . Exercise challenges were performed after oral administration of 1.5 mg/kg oxatomide or placebo in eight asthmatic children in a double-blind placebo-controlled study . Oxatomide produced acute bronchodilatation with 6.1 % improvement on an average in FEV1 . The mean maximal % fall obtained by oxatomide was 13.5 % , while that by placebo was 22 % ( P < .05 ) . These results indicate that oxatomide reduces nonspecific bronchial hyperresponsiveness A combination dose aerosol of fenoterol hydrobromide ( 200 micrograms ) and ipratropium bromide ( 80 micrograms ) was compared with aerosolized salbutamol ( 200 micrograms ) in 10 stable asthmatic patients . With both treatments a statistically significant improvement was noticed in both FEV1 and PEF measurements starting after 15 minutes and continuing until 330 to 360 minutes . No statistically significant differences in one second Forced Vital Capacity ( FEV1 ) and Peak Expiratory Flow ( PEF ) was noted between the two treatments . No side effect was noticed . As a result , it was concluded that in bronchial asthmatic patients , the bronchodilator effects of the combination of a beta-2 agonist with anticholinergic drugs was as effective and lasted as long as salbutamol . This combination , in order to prevent cardiovascular complications , could be selected as a suitable treatment for those patients who need high doses of beta-2 agonist drugs Summary A vagal mechanism appears to be involved in the development of exercise-induced asthma ( EIA ) , although previous studies have failed to demonstrate a protective effect of anticholinergic drugs against post-exercise bronchoconstriction . To reassess this hypothesis the effect of a new anticholinergic drug , Oxitropium Bromide ( OTB ) has been studied in ten subjects with documented EIA.There was no change after inhalation of a placebo . Administration of OTB led to bronchodilatation and totally blocked post-exercise bronchoconstriction in 7 patients , and it did so partly in 2 . The response to the drug appeared to depend on pretest respiratory function . Thus , the anticholinergic drug OTB may protect against EIA in most patients , confirming the role of a vagal cholinergic mechanism in EIA arthritis of the right hip . It was then discovered that he had had mild diarrhoea for over 10 years . On examination there were no significant abnormal physical signs except restricted movements of his right hip ; no abdominal tumour could be felt . Sigmoidoscopy revealed a moderate degree of proctitis and biopsy showed the features of chronic ulcerative colitis , but there was no premalignant change in the rectal mucosa . Barium enema revealed extensive ulcerative colitis with a constant stricture in the transverse colon ( fig. 2 ) . At operation 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 Eighteen children between 6 and 14 years of age with perennial asthma were studied over two four-week treatment periods . Ipratropium bromide , given in addition to their current treatment , was compared with placebo using a double-blind crossover technique . The period of treatment with ipratropium was associated with a significant reduction in symptoms during both day and night and significantly higher morning peak expiratory flow rates IPRATROPIUM BROMIDE is a quaternary isopropyl derivative of the muscarinic antagonist atropine that has bronchodilator properties when administered topically via the respiratory airways . Because of its quaternary nature , it is poorly absorbed into the bloodstream after direct application into the bronchial tree ; the cardiovascular side effects are thus minimal . For these reasons ipratropium could represent a significant advance in therapy , especially considering its alternative mode of action via blockade of the cholinergic system rather than stimulation of ~adrenoceptors . Initial information on ipratropium solution has indicated that a dose of 250 # g can be given safely to preschool children with asthma and that the bronchodilation is comparable to that achieved by salbutamol . ~ The purpose of our study was to determine the optimal dosage of ipratropium solution  when administered by aqueous nebulization , by constructing a dose-response curve in children of school age . NEBULIZED specific beta-2 agonists such as salbutamol ( albuterol ) are widely preferred as the first-line drugs of choice for treating acute asthma in Children . Many studies have shown their efficacy as well as convenience in delivery ) , 2 Administration of frequent small doses ( 50 t ~ g/kg/dose every 20 minutes ) of nebulized salbutamol is safe and superior to the more conventional hourly dosing ( 150 /~g/kg/dose ) , producing a smoother rise in forced expiratory volume in 1 second and an earlier peak response without deterioration between doses ) However , even with this aggressive approach , significant residual airways obstruction remains despite additional doses of salbutamol . This suggests that the residual airways obstruction is related to factors unresponsive to beta-2 bronchodilators , such as mucosal edema , secretions , or cholinergic bronchomotor .tone . Ipratropium bromide is a quaternary ammonium derivative of atropine . When delivered by inhalation , it produces a local anticholinergic effect with no systemic absorption ? . 5 It is a potent bronchodilator , comparable to beta-2 agonists , and has been found to be very Useful , especially in adults with chronic bronchitis ? . 5 Our study was design ed to determine whether ipratropium bromide , by its anticholinergic action , could improve the residual airways obstruction seen after treatment with salbutamol alone . STUDY OBJECTIVE To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV beta-agonists , inhaled ipratropium , and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU ( PICU ) . DESIGN A prospect i ve , r and omized , controlled trial . Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment . SETTING The PICU of an urban , university-affiliated , tertiary-care children 's hospital . PATIENTS Children with a diagnosis of status asthmaticus who were admitted to the PICU for < or = 2 h and who were in severe distress , as indicated by a modified Wood-Downes clinical asthma score ( CAS ) of > or = 5 . INTERVENTIONS All subjects initially received continuous albuterol nebulizations ; intermittent , inhaled ipratropium ; and IV methylprednisolone . The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 microg/mL. A CAS was tabulated twice daily . MEASUREMENTS AND RESULTS Forty-seven children ( median age , 8.3 years ; range , 13 months to 17 years ) completed the study . Twenty-three children received theophylline  . The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group . All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion . Among the 41 subjects who were not receiving mechanical ventilation , those receiving theophylline achieved a CAS of < or = 3 sooner than control subjects ( 18.6 + /- 2.7 h vs 31.1 + /- 4.5 h ; p < 0.05 ) . Theophylline had no effect on the length of PICU stay or the total incidence of side effects . Subjects receiving theophylline had more emesis ( p < 0.05 ) , and control patients had more tremor ( p < 0.05 ) . CONCLUSIONS Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol , ipratropium , and methylprednisolone . The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined Postexertional wheezing is an important clinical sign of nonspecific airway hyperreactivity . We have studied wheezing after exercise in 6 asthmatic subjects , 13 to 20 yr of age , using spectral analysis of recorded tracheal sounds . Automated spectral characterization was used to measure wheezing as a proportion of respiratory time . Anticholinergic treatment with ipratropium bromide ( Atrovent ) was compared with placebo to investigate effects on postexertional wheezing , and pulmonary function was compared with the result of respiratory sound analysis . Atrovent did not abolish exercise-induced bronchospasm but improved preexercise lung function and thereby caused a parallel upward shift in the response curves . Wheezing after Atrovent was significantly less , later in onset , and mainly expiratory at 20 min after exercise . Wheezing as a percentage of total respiratory time correlated well with FEV1 , Vmax50 , and SGaw . Analysis of respiratory sounds and automated quantification of wheezing may be a useful complementary test of bronchial obstruction in asthma 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 In a double-blind study in 23 asthmatic patients Sch 1000 was found to be an effective bronchodilator with an onset of effect within 15 minutes and a duration of four hours . It was effective on both small and large airways Two groups of eight asthmatic children carried out serial treadmill exercise tests at 2‐hourly intervals , after double‐blind premedication with oxatomide ( 2 mg/kg by mouth ) , sodium cromoglycate powder ( 20 mg by inhalation ) or matched placebo preparations . The drugs were studied in one group up to 6 hr and in the other group ( omitting sodium cromoglycate ) from 4 to 10hr after administration . Peak expiratory flow rate was measured before and after exercise to give an index of exercise‐induced asthma A double-blind crossover study was performed on 33 children with asthma to compare the effectiveness of nebulized solutions of preservative-containing and preservative-free ipratropium bromide . Both solutions produced bronchodilation . No significant differences were found between the two solutions at any time after nebulization in minimum and maximum changes from baseline value or in the areas under the lung function time curves . The presently formulated preservative-containing ipratropium bromide solution was not shown to be inferior to a preservative-free compound The combination of nebulized atropine methylnitrate ( AMN ) and a beta-agonist has been shown to produce greater and longer lasting bronchodilation than either drug alone . We examined the efficacy of the combination in diminishing the " morning dipping " in PEFR in eight hospitalized but stable asthmatics . The patients received nebulized albuterol along with either AMN ( AMN + ALB ) or placebo ( ALB ) in a r and om double-blind cross-over fashion at 10 PM on four nights . PEFR and FEV1 were recorded at 6 PM , 10 PM , and 6 AM before the administration of bronchodilators . There was no statistically significant difference between ALB and AMN + ALB in reducing the morning dipping in these patients The study was carried out on 19 patients with moderate and severe bronchial asthma . During three days after the initial spirometric evaluation the patients received -- on the first day 0.5 mg of pirenzepine in nebulization ( P ) , on the second day 0.25 mg of ipratropium bromide ( IB ) , on the third day both substances together . Ventilatory parameters were monitored on the 5th , 20th , 40th and 60th minute following nebulization . The observed parameters did not differ significantly between both groups . Pirenzepine given after ipratropium bromide increased FEV1 from 1.89 L to 2.37 L ( p < 0.01 ) . The observed results imply that pirenzepine given with ipratropium bromide induce a significant bronchodilating effect and could be added to therapy of bronchial asthma Abstract Objectives : To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children . Design : R and omised , double blind , placebo controlled trial . Setting : Community based study in Southampton . Subjects : 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months . Interventions : After a run in period of 2–6 weeks children were r and omly allocated twice daily inhaled beclomethasone dipropionate 200 μg or placebo through a Diskhaler for 6 months with a wash out period of 2 months . Children were assessed monthly . Main outcome measures : Forced expiratory volume in 1 second ( FEV1 ) ; bronchial responsiveness to methacholine ( PD20 ) ; percentage of days with symptoms of upper and lower respiratory tract infection with frequency , severity , and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate . Results : During the treatment period there was a significant increase in mean FEV1 ( 1.63 v 1.53 l ; adjusted difference 0.09 l ( 95 % confidence interval 0.04 to 0.14 ) ; P=0.001 ) and methacholine PD20 ( 12.8 v 7.2 μmol/l ; adjusted ratio of means 1.7 ( 1.2 to 2.4 ) ; P=0.007 ) in children receiving beclomethasone dipropionate compared with placebo . There were , however , no significant differences in the percentage of days with symptoms or in the frequency , severity , or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups . Conclusions : Although lung function is improved with regular beclomethasone dipropionate 400 μg/day , this treatment offers no clinical ly significant benefit in school age children with wheezing episodes associated with viral infection . Key messages Increasing evidence suggests that episodic wheezing in children in association with viral infections is a separate entity from atopic asthma Although inhaled corticosteroids are beneficial in asthma , their role in treating wheezing associated with viral infections is unclear In this study regular inhaled corticosteroids result ed in improved lung function and decreased bronchial responsiveness but did not have any effect on episodes of wheezing Inhaled corticosteroids are of little benefit in children with episodic wheezing associated with viral frequent development of tachyphylaxis apart from numerous other toxic reactions and the painfulness of the injections . The main advantage of dimercaprol is that the molecule is not charged , is soluble in lipids , and is able to cross the blood-brain barrier fairly easily compared with penicillamine , trientine dihydrochloride , and unithiol , which are highly charged . Treatment with unithiol was started in two other patients . The first developed a fever of 39"C four hours after the test dose and a 50 ° , fall in the leucocyte count . A further challenge dose caused a similar reaction and treatment was not pursued . This patient was subsequently managed with tetrathiomolyb date .3 The second patient took unithiol for 10 days before refusing it because of intense nausea and a change in taste . Other patients have received single test doses , and the result ing cupruresis has been comparable with that after penicillamine and trientine dihydrochloride in most cases . Unithiol may well prove to be yet one more fall back treatment for patients who develop intolerance to penicillamine The bronchodilatory activity of Berodual in comparison to Fenoterol and Ipratropium Bromide was investigated in a group of 59 children aged 8 - 15 years , suffering from mild bronchial asthma in a symptoms-free period . The relaxing activity was monitored dynamically by means of the analysis of flow-volume curve measurements . We have found that the bronchodilatory activity of Berodual was faster , stronger and longer in comparison to Fenoterol and Ipratropium Bromide : The efficacy of adding oral or inhaled atropine sulphate to the maintenance therapy of 12 children with severe chronic asthma was assessed using a double blind crossover study lasting three months . There was no obvious subjective or objective clinical difference between either form of atropine sulphate and placebo . Twice daily peak flow rates were not significantly different for the three treatment periods . However , during oral atropine therapy there was a significant improvement in FEV1/ VC ( P < 0.05 ) and in RV/TLC ( P < 0.05 ) compared to placebo . Inhaled atropine had no significant effect on baseline pulmonary function testing . No side effects were encountered . Further clinical trials are necessary to confirm the beneficial effect of long term oral atropine sulphate in the treatment of children with severe chronic asthma In a double blind r and omized study during a period of 2 weeks we compared the therapeutic effectiveness and side effects of IK-6-Inhaletten ( 0.1 mg Fenoterol + 0.04 mg Ipratropiumbromide ) and SCH 1000-Inhaletten ( 0.2 mg Ipratropiumbromide ) in 39 children ( 4 - 14 years ) suffering from mild , moderate or severe asthma bronchiale . All measurements were performed with a whole body plethysmograph . In contrast to SCH 1000-inhalation after inhalation of IK-6-Inhaletten , we found a good improvement of the total airway resistance Rtot , the specific airway resistance SRaw and the forced exspiratory volume FEV1 . Especially SRaw was significantly diminished compared to the less effective SCH 1000-inhalation . IK-6-inhalation allowed to decrease the amount of bronchospasmolytic therapy in our group of patients . We did not observe any severe side effects after inhalation of IK-6 or SCH 1000 . In summary , we recommend the application of the IK-6-Inhaletten in children suffering from mild and moderate asthma bronchiale 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 A blind r and omized cross-over comparative study of salbutamol and the combination fenoterol/ipratropium was carried out in 20 patients with mild to moderate bronchial asthma ; clinical and functional serial parameters were evaluated . The combination was more effective than salbutamol in preventing crisis and incidence of cough and wheezing , and in the spirometric results . There were no significant differences in expectoration and the functional parameters improved not only in flow but also in volume . Pathogenesis is discussed
BACKGROUND In the intrinsic system of controlling airway calibre , the cholinergic ( muscarinic ) sympathetic nervous system has an important role .
Anticholinergic , anti muscarinic bronchodilators such as ipratropium bromide are frequently used in the management of childhood airway disease .
In asthma , ipratropium is a less potent bronchodilator than beta-2 adrenergic agents but it is known to be a useful adjunct to other therapies , particularly in status asthmaticus .
What remains unclear is the role of anticholinergic drugs in the maintenance treatment of chronic asthma .
OBJECTIVES To determine the effectiveness of anticholinergic drugs in chronic asthma in children over the age of 2 years .