Inadequate use of asthma medication in the United States: results of the asthma in America national population survey. Comparison between fenoterol and fenoterol plus oxitropium bromide delivered by metered-dose inhaler with InspirEase to relieve acute asthma attack. NEBULISED SALBUTAMOL WITH AND WITHOUT IPRATROPIUM BROMIDE IN ACUTE AIRFLOW OBSTRUCTION The combination of fenoterol and ipratropium bromide in bronchial asthma: comparison of the acute effects of two different dosages. The effect of adding ipratropium bromide to salbutamol in the treatment of acute asthma: a pooled analysis of three trials. Effect of continuously nebulized ipratropium bromide plus albuterol on emergency department length of stay and hospital admission rates in patients with acute bronchospasm. A randomized, controlled trial. Nebulized ipratropium in the treatment of acute asthma. What are minimal important changes for asthma measures in a clinical trial? Nebulized atropine sulfate in the treatment of acute asthma. Severe exacerbations of COPD and asthma. Incremental benefit of adding ipratropium to usual therapy. Ipratropium bromide in acute asthma. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. Superiority of ipratropium plus albuterol over albuterol alone in the emergency department management of adult asthma: a randomized clinical trial. Nebulized salbutamol with and without ipratropium bromide in the treatment of acute asthma. Admissions to Canadian hospitals for acute asthma: a prospective, multicentre study. Efficacy of adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device in adults with acute severe asthma. Relative efficacy of nebulised ipratropium bromide and fenoterol in acute severe asthma. Comparison of Acute Bronchodilator Effects of Inhaled Ipratropium Bromide and Salbutamol in Bronchial Asthma [Clinical pharmacological trials of a new metered dose inhaler, IK-6, a combination of the bronchodilators fenoterol and ipratropium bromide (author's transl)]. Need for theophylline in severe steroid‐requiring asthmatics Levalbuterol Versus Levalbuterol Plus Ipratropium in the Treatment of Severe Acute Asthma Comparison of nebulized salbutamol with nebulized ipratropium bromide in acute asthma. Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma. Oxitropium bromide: an acute dose response study of a new anticholinergic drug in combination with fenoterol in asthma and chronic bronchitis. Double blind comparison of acute bronchial and ventilation-perfusion changes to atrovent and isoproterenol. A comparison of ipratropium and albuterol vs albuterol alone for the treatment of acute asthma. Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. A randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma. The clinical efficacy of combination nebulized anticholinergic and adrenergic bronchodilators vs nebulized adrenergic bronchodilator alone in acute asthma. Canadian Combivent Study Group. Efficacy of atropine sulfate in combination with albuterol in the treatment for acute asthma. Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. Nebulization versus injection in ambulatory treatment of acute asthma: a comparative study. Should ipratropium bromide be added to beta-agonists in treatment of acute severe asthma? Rapid improvement of peak flow in asthmatic patients treated with parenteral methylprednisolone in the emergency department: A randomized controlled study. [Effects of ipratropium bromide (IPB) and its combination with salbutamol sulfate (SAS) in acute asthmatic attack]. First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department. Nebulized ipratropium bromide in the treatment of acute asthma. Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of asthma. Blind randomized cross-over comparative study of salbutamol and the combination fenoterol-ipratropium IK6 in patients with bronchial asthma. Therapeutic equivalence of a novel HFA134a-containing metered-dose inhaler and the conventional CFC inhaler (Berodual) for the delivery of a fixed combination of fenoterol/ipratropium bromide. A randomized double-blind placebo-controlled crossover study in patients with asthma.
BACKGROUND Studies of the use of anti-inflammatory asthma therapy have been limited to selected population s or have been unable to assess the appropriateness of therapy for individuals . OBJECTIVE We sought to describe the current use of asthma medication in the United States population and to examine the influence of symptoms and sociodemographics on medication use . METHODS This study was based on a cross-sectional , national , r and om-digit-dial household telephone survey in 1998 design ed to identify adult patients and parents of children with current asthma . Respondents were classified as having current asthma if they had a physician 's diagnosis of asthma and were either taking medication for asthma or had asthma symptoms during the past year . RESULTS One or more persons met the study criteria for current asthma in 3273 ( 7.8 % ) households in which a screening question naire was completed . Of these , 2509 persons ( 721 children < 16 years ) with current asthma were interviewed . Current use of anti-inflammatory medication  was reported by 507 ( 20.1 % ) . Of these , most were using  inhaled corticosteroids  ( 72.5 % ) , with use of antileukotrienes reported by 11.4 % and use of cromolyn-nedocromil reported by 18.6 % . Of persons with persistent asthma symptoms in the past month , 26.2 % reported current use of some form of anti-inflammatory medication .  In bivariate analysis persons reporting lower income , less education , and present unemployment , as well as smokers , were significantly ( P < .001 ) less likely to report current anti-inflammatory use than were other population s. In a multiple regression model nonsmokers and those of white , non-Hispanic ethnicity , as well as persons reporting less asthma control , were more likely to report current anti-inflammatory medication use . CONCLUSION In the United States use of appropriate asthma therapy remains inadequate . Strategies to increase use of anti-inflammatory therapy  among patients with asthma are needed . These might include methods to increase access to asthma care for minorities and the socioeconomically disadvantaged Although the inhalation of beta2-agonists has frequently been used to relieve acute asthma attacks , the efficacy of anticholinergic agents for acute asthma attacks still remains unclear . This study was design ed to compare the inhalation of fenoterol and the inhalation of fenoterol plus oxitropium bromide delivered by a metered-dose inhaler with holding chamber ( InspirEase ) to relieve acute asthma attacks . To accomplish this , 69 patients who had presented with an acute asthma attack were r and omized to receive either fenoterol ( 1 puff [ 200 microg/puff ] every 1 min for 5 min ; total 1000 microg ) or fenoterol plus oxitropium bromide ( 2 puffs [ 100 microg/puff ] every 1 min for 5 min ; total 1000 microg ) . The peak expiratory flow ( PEF ) and forced expiratory volume in 1 sec ( FEV1 ) values were measured before treatment , and 1 , 15 , 30 , and 60 min after the inhalation therapy . The ratios of improvement , PEF ( or FEV1 ) after treatment divided by PEF ( or FEV1 ) before treatment , were also calculated . Thirty-three patients were evaluated in the combination group and 31 patients were evaluated in the  fenoterol group . The PEF value at 60 min after inhalation therapy of the fenoterol plus oxitropium bromide group ( 261 + /- 18 L/min , mean + /- st and ard error ) was significantly higher compared to that of the fenoterol group ( 210 + /- 17 L/min ) . In addition , the ratios of improvement of PEF at 1 , 15 , 30 , and 60 min after inhalation therapy were significantly higher in the fenoterol plus oxitropium bromide group compared with the fenoterol group 103 patients with acute airflow obstruction ( 56 asthma , 47 chronic obstructive pulmonary disease [ COPD ] ) completed a double-blind trial of nebulised bronchodilator treatment in a hospital accident and emergency department . Each patient was r and omised to receive either 10 mg of salbutamol nebuliser solution in 2 ml of saline or 10 mg of salbutamol in 2 ml ( 0.5 mg ) of preservative-free ipratropium bromide .  Peak flow rate ( PFR ) was recorded before treatment and 1 hour after beginning nebulised treatment . In 23 asthmatic patients given salbutamol alone PFR rose by a mean 31 % 1 hour after treatment whereas in 33 such patients given combined treatment it rose by a mean 77 % ( 95 % confidence interval for the difference 8 - 84 % ) . Patients whose PFR was below 140 l/min at entry gained maximum benefit from the combined treatment . For COPD patients the PFR rise was almost identical for both treatments . In acute asthma the immediate PFR response to a mixture of salbutamol and ipratropium bromide was better than the response to nebulised salbutamol alone . For COPD patients , the two treatments were of equal benefit Combinations of beta-stimulant and anticholinergic drugs have been advocated as a potentially useful tool in the treatment of  reversible airway obstruction .  We investigated the effectiveness and safety of a metered aerosol preparation delivering fenoterol 100 micrograms and ipratropium bromide 40 micrograms per puff : two dosages ( 2 puffs and 4 puffs ) were used in 16 asthmatic patients , and their acute effects ( up to 420 min ) were investigated in a double-blind r and omized trial . The results point out a reasonably good response to both dosages , with no notable difference between them as far as vital capacity , FEV 1 , MMEF and Vmax75 are concerned . This finding indicates the possibility of achieving a satisfactory bronchodilation at beta-stimulant dosages far lower than the st and ard ones commonly used and therefore minimizing the risk of untoward cardiovascular effects OBJECTIVE To assess the effect on FEV1 and clinical outcomes of adding ipratropium bromide to salbutamol in the treatment of acute asthma . METHODS We conducted a pooled analysis of three r and omized double-blinded clinical trials conducted in the United States , Canada , and New Zeal and . The studies enrolled 1,064 patients aged 18 to 55 years who presented at the emergency department with acute asthma . Patients were r and omized to treatment with a combination of nebulized 2.5 mg salbutamol plus 0.5 mg ipratropium bromide , or 2.5 mg salbutamol alone .  Medications were administered at baseline and , in the US study , at 45 min . FEV1 was measured at baseline , 45 min , and 90 min . Patients were followed up for 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization . RESULTS Treatment groups were comparable at baseline . Of the 1,064 patients r and omized , 1,015 patients ( 95 % ) remained in the study for measurement at 45 min , and 961 patients ( 90 % ) completed the final measurement at 90 min . Comparison of overall improvement in FEV1 at 45 min indicated a better response for patients receiving combination therapy ( mean difference=43 mL , 95 % confidence interval [CI]=-20 , 107 ) . The distribution of change in FEV1 was skewed by a small number of patients with extreme values ( 38 of 1,064=3.6 % ) that may have been due to unreliable lung function testing . Removing these outliers produced a larger and more precise estimate of effect ( mean difference=55 mL , 95 % CI=2,107 ) . Because the distribution was skewed , we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy . The difference between median values at 45 min is 40 mL ( Wilcoxon p value=0.03 ) . In addition , 4.9 % ( 95 % CI=-1 % , 11 % ) more patients in the combination group achieved at least 20 % of their potential improvement , as measured by the difference between their baseline FEV1 and their predicted FEV1 . Patients receiving combination therapy had lower risk for each of three clinical outcomes : the need for additional treatment ( relative risk [RR]=0.92 , 95 % CI=0.84 , 1.0 ) , risk of asthma exacerbation ( RR=0.84 , 95 % CI=0.67 , 1.04 ) , and risk of hospitalization ( RR=0.80 , 95 % CI=0.61 , 1.06 ) . CONCLUSION Adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function , and reduces the risk of the need for additional treatment , subsequent asthma exacerbations , and hospitalizations . These apparent benefits of adding ipratropium bromide were independent of the amount of beta-agonist that had been used earlier in the attack , and possibly related to a recent upper respiratory tract infection . Confirmatory studies are needed , especially for clinical outcomes OBJECTIVE To compare the outcome of patients with acute bronchospasm treated with continuously nebulized albuterol plus ipratropium bromide vs albuterol alone . SETTING The Emergency Department ( ED ) at the University of California San Francisco Medical Center . PARTICIPANTS Patients > or = 18 years old presenting to the ED with acute bronchospasm and a peak expiratory flow rate ( PEFR ) of < 70 % predicted . INTERVENTIONS This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . Subjects were treated with either a combination of albuterol ( 10 mg/h ) plus ipratropium bromide ( 1.0 mg/h ) or albuterol alone via continuous nebulization for a maximum of 3 h. Vital signs , Borg dyspnea score , and PEFR were recorded hourly . Primary outcome measures were improvement in PEFR , hospital admission rates , and length of stay in the ED . MEASUREMENTS AND RESULTS Data was analyzed for 67 subjects . The mean age ( -/+ SD ) was 47.5+/-18.8 , and mean initial PEFR was 44.8+/-12.5 % of predicted . The median length of stay for all subjects was 225 min , and 31 % of all subjects were admitted . Patients given combination therapy averaged 6.3 % greater improvement in PEFR compared with control subjects ( 95 % confidence interval [ CI ] , -15 % to 27 % . The odds ratio for admission with combination therapy was 0.88 ( 95 % CI , 0.28 to 2.8 ) . The median length of stay in the ED was 35 min shorter for those receiving combination treatment ( 210 vs 245 min ; p = 0.03 ) . However , when adjusted for initial PEFR , there was no statistically significant difference ( p = 0.26 ) . CONCLUSION Although the direction of all three outcome measures favored combination therapy , there was no statistically significant difference between ED patients with acute bronchospasm receiving continuous albuterol plus ipratropium bromide and those receiving albuterol alone The efficacy of ipratropium and salbutamol was determined in 117 patients with acute asthma who presented to an emergency department to determine whether the order of administration of the two agents affects the improvement in peak flow rates . Patients were given two nebulized treatments at an interval of one hour in a r and omized , double-blind design . They received either 5 mg nebulized salbutamol followed by 0.5 mg ipratropium , ipratropium followed by salbutamol , or both drugs administered together followed by nebulized saline . Ipratropium was an effective bronchodilator when given as the first agent . Simultaneous administration with salbutamol was as effective as sequential administration . At one hour after treatment , there was no difference in peak flow between the combination of drugs and either drug given alone . Ipratropium given after salbutamol was not superior to saline solution given after the combination of drugs . Our data do not suggest a substantial therapeutic effect from addition of ipratropium to salbutamol in the immediate treatment of acute asthma In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist .  Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change Conflicting reports have appeared concerning the role of anticholinergic agents in the treatment of acute asthma . This study was design ed to determine whether atropine sulfate , the only anticholinergic agent currently available in the United States for nebulization , increases bronchodilation when added to an inhaled beta-adrenergic agonist during the initial treatment of an acute asthma attack . Adults asthmatics ( n = 40 ) with acute asthma attacks were r and omized to receive metaproterenol ( 5 percent solution , 0.3 ml ) either alone or with atropine sulfate ( 2.5 mg ) , by nebulization . Spirometry , vital signs , and the presence of side effects 0 , 30 , 60 , and 120 minutes after treatment were determined . There were no significant differences between the metaproterenol alone and metaproterenol plus atropine sulfate groups in regard to age , duration of asthma , baseline spirometry , or side effects . No differences were noted between the two groups regarding changes in FEV1 and FVC from baseline ( expressed in milliliters or as a percentage of baseline ) during the observation period . We conclude that nebulized atropine sulfate yields no additional benefit when added to metaproterenol during the initial treatment of an acute asthma attack Single dose studies have assessed the utility of ipratropium bromide alone or with beta agonists in the short- and long-term management of chronic obstructive lung disease and asthma . We performed a r and omized , double-blind trial to assess the incremental benefit over 24 hours of adding ipratropium vs placebo to a st and ardized regimen of medications commonly used in the acute and subsequent hospital management of COPD and asthma . Sixty-eight subjects received nebulized salbutamol , intravenous methylprednisolone , intravenous aminophylline , and antibiotics  and were r and omized to receive either 80 micrograms of ipratropium or placebo via metered dose inhaler and spacing device with each salbutamol treatment ( 6 to 8 times per day ) . Among the 50 patients who completed the study , there were no significant differences between ipratropium and placebo groups with respect to baseline FEV1 , FVC , and PaCO2 . The improvement of FEV1 from baseline to 24 hours was 294 ( SD = 568 ) ml in the ipratropium group vs 393 ( SD = 622 ) ml in placebo group . Adjusting FEV1 by age , gender , and smoking did not significantly alter the findings . Those with an admission diagnosis of asthma showed larger 24 hour FEV1 responses ( 487 ml in ipratropium vs 801 ml in placebo ) than those with COPD ( 149 ml ipratropium vs 102 ml in placebo ) . However , within these two strata , there were no significant differences in FEV1 improvement between ipratropium and placebo groups . This study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma , it could safely be discontinued by 24 hours in order to reduce the cost and complexity of therapy 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 BACKGROUND Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment . Tiotropium , a long-acting inhaled anticholinergic agent , might be an effective bronchodilator in such patients . OBJECTIVE We sought to compare the efficacy and safety of 2 doses of tiotropium ( 5 and 10 μg daily ) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma ( Asthma Control Question naire score , ≥ 1.5 ; postbronchodilator FEV₁ , ≤ 80 % of predicted value ) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a long-acting β₂-agonist . METHODS This was a r and omized , double-blind , crossover study with three 8-week treatment periods . The primary end point was peak FEV₁ at the end of each treatment period . RESULTS Of 107 r and omized patients ( 54 % female patients ; mean , 55 years of age ; postbronchodilator FEV₁ , 65 % of predicted value ) , 100 completed all periods . Peak FEV₁ was significantly higher with 5 μg ( difference , 139 mL ; 95 % CI , 96 - 181 mL ) and 10 μg ( difference , 170 mL ; 95 % CI , 128 - 213 mL ) of tiotropium than with placebo ( both P < .0001 ) . There was no significant difference between the active doses . Trough FEV₁ at the end of the dosing interval was higher with tiotropium ( 5 μg : 86 mL [ 95 % CI , 41 - 132 mL ] ; 10 μg : 113 mL [ 95 % CI , 67 - 159 mL ] ; both P < .0004 ) . Daily home peak expiratory flow measurements were higher with both tiotropium doses . There were no significant differences in asthma-related health status or symptoms . Adverse events were balanced across groups except for dry mouth , which was more common on 10 μg of tiotropium . CONCLUSION The addition of once-daily tiotropium to asthma treatment , including a high-dose inhaled corticosteroid plus a long-acting β₂-agonist , significantly improves lung function over 24 hours in patients with inadequately controlled , severe , persistent asthma STUDY OBJECTIVE The use of nebulized ipratropium in combination with beta-agonists for the treatment of acute asthma in adults is controversial . We wished to test the hypothesis that combined aerosol treatment results in a greater rate of airflow improvement and a lower proportion of hospital admission in adults with acute asthma . METHODS In a r and omized , double-blind , placebo-controlled trial , 55 adult asthmatic patients with peak expiratory flow rate ( PEFR ) less than 200 L/min were r and omly assigned to nebulization treatment with albuterol alone ( 2.5 mg initial dose followed by 2 more doses at 20-min intervals . ) , or the same albuterol regimen plus ipratropium ( .5 mg combined with the initial dose of albuterol only ) . Patients were recruited from an emergency department at an urban academic medical center . The primary endpoints were changes in PEFR and in percent predicted PEFR over time ( ie , treatment by time effect ) . PEFRs were assessed at baseline and at 20-minute intervals for a 1-hour period . The proportion of admissions in the two groups were examined as secondary endpoints . RESULTS The increases in PEFR and percent predicted PEFR over time were both significantly greater in the combined ipratropium plus albuterol treatment group ( P < or = .001 ) . In addition , the proportion admitted patients was less in this group ( 3/27 ) than the proportion in the albuterol-only group ( 10/28 ) . The 95 % confidence interval for the absolute difference of 25 % in the proportion admitted was 3 % to 46 % , P = .03 . Most of the baseline clinical and historical features in the two groups were similar . CONCLUSION These data suggest that ipratropium should be combined with initial albuterol nebulization in the ED treatment of acute asthma in adults , especially those with PEFRs less than 200 L/min BACKGROUND Routine addition of ipratropium bromide to beta-agonist therapy in acute asthma is of uncertain benefit . OBJECTIVE This study was carried out to evaluate : ( 1 ) whether nebulized ipratropium ( 0.5 mg ) plus salbutamol ( 2.5 mg ) ( Combivent ) confers additional bronchodilation over nebulized salbutamol ( 2.5 mg ) alone in patients with acute asthma and ( 2 ) whether adjustment for prognostic indicators of outcome influences any benefit seen with ipratropium . METHODS A double-blind , two-center , r and omized , single-dose study was performed in 338 patients with asthma , aged 18 to 55 years , who attended the emergency department for treatment of acute asthma . The primary end point was FEV1 at 90 minutes . RESULTS The mean absolute difference in FEV1 at 90 minutes for Combivent compared with salbutamol was 113 ml ( SEM + /- 48 ml , p < 0.05 ) . Independent of the study drug received , a poor response to treatment was predicted by frequent use of inhaled beta-agonist before presentation ( p < 0.0001 ) , severity of the attack ( p < 0.05 ) , and longer duration of attack ( p < 0.05 ) . Subjects who had taken more than 10 puffs of inhaled beta-agonist through a metered-dose inhaler or who had serum salbutamol levels of greater than 2 mmol/L on presentation demonstrated no benefit from the addition of ipratropium . Patients with an FEV1 less than 1 L on presentation also responded less well to Combivent , which was explained by the association between severity of attack and greater use of inhaled beta-agonist therapy . CONCLUSION A single dose of nebulized Combivent confers additional bronchodilation over salbutamol alone ( p < 0.05 ) in acute asthma . Patients who exhibited most benefit from the addition of ipratropium were those who had consumed the least inhaled beta-agonist before presentation , not those with the most severe asthma BACKGROUND Asthma exacerbations constitute one of the most common causes of emergency department ( ED ) attendance in most developed countries . While severe asthma often requires hospitalization , variability in admission practice s has been observed . OBJECTIVE To describe the factors associated with admission to Canadian hospitals for acute asthma after ED treatment . METHODS Subjects 18 to 55 years of age treated for acute asthma in 20 Canadian EDs prospect ively underwent a structured ED interview  ( n=695 ) and telephone interview two weeks later . RESULTS The median age of the patients was 30 years , and the majority were women ( 62.8 % ) . The admission rate was 13.1 % ( 95 % CI 10.7 % to 15.8 % ) . Admitted patients were older , more often receiving oral or inhaled corticosteroids at presentation , and more frequently receiving systemic corticosteroids and magnesium sulphate in the ED . Similar proportions received  beta-2 agonists and /or ipratropium bromide  within 1 h of arrival . On multivariable analyses , factors associated with admission included age , previous admission in the past two years , more than eight beta-2 agonist puffs in the past 24 h , a Canadian Triage and Acuity Score of 1 to 2 , a respiratory rate of greater than 22 breaths/min and an oxygen saturation of less than 95 % . CONCLUSION The admission rate for acute asthma from these Canadian EDs was lower than reported in other North American studies . The present study provides insight into practical factors associated with admission for acute asthma and highlights the importance of history and asthma severity markers on ED decision making . Further efforts to st and ardize ED management and expedite admission decision-making appear warranted BACKGROUND The efficacy of combination therapy adding multiple doses of anticholinergics to beta(2)-agonists to improve outcome has not been established in adults with acute severe asthma . OBJECTIVE This study was undertaken to compare the outcome of adults with acute severe asthma treated with 4 puffs of salbutamol ( 100 microg/actuation ) every 20 minutes for 3 doses plus 4 puffs of oxitropium bromide ( 100 microg/actuation ) with each of the 3 salbutamol doses versus salbutamol alone administered by means of a metered-dose inhaler with a spacer device . METHODS A r and omized , single-blind , placebo-controlled study was performed in 74 patients between 18 and 55 years old presenting to the emergency department ( ED ) for treatment of acute asthma with a peak expiratory flow ( PEF ) of 50 % or less than the normal predicted value . The primary endpoint was improvement in PEF over the course . The secondary endpoint was the need for additional ED treatment at 120 minutes . RESULTS The increase in PEF over the course was significantly greater in the oxitropium plus salbutamol treatment group ( P < .0001 ) . The mean absolute difference in PEF at 120 minutes for combination therapy compared with salbutamol alone was 37.8 L/min ( P = .001 ) . In addition , the proportion of need for additional ED treatment was less in the combination group than the group receiving salbutamol alone ( odds ratio , 0.32 ; 95 % confidence interval , 0.11 - 0.90 ) . CONCLUSION Adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device for acute severe asthma produces a significant improvement in lung function and reduces the need for additional ED treatment In a double-blind , r and omised , controlled clinical trial of 145 patients with acute asthma , the efficacy of nebulised  4-hourly ipratropium bromide plus 4-hourly fenoterol ( group I , 50 patients ) , 2-hourly fenoterol ( group II , 50 patients ) and 4-hourly fenoterol ( group III , 45 patients ) was assessed . All patients received an optimal infusion of aminophylline and 81 patients ( 27 in each group ) received hydrocortisone for clinical indications . It was found that cholinergic side-effects in group I were not more common than in group II . Tremor was more common in group II . Assessment of bronchodilator efficacy was confined to the 81 patients whose therapy included hydrocortisone .  Peak expiratory flow rate , forced expiratory volume in 1 second , and forced vital capacity were expressed as a percentage of predicted for each individual and the mean values for each group plotted . It was found that the response rate , as assessed by the area under the curve , was significantly more rapid in group I compared with both group II ( P less than 0.001 ) and group III ( P less than 0.005 ) . These findings were consistent for all three lung function measurements . However , there was no significant difference in the responses between group II and group III . It is concluded that adding ipratropium bromide to conventional regimens is likely to benefit patients with acute asthma Both salbutamol ( sal ) and ipratropium ( ipra ) are effective bronchodilators in asthma patients . However , the issue of their relative status remains unresolved and the clinical factors affecting the responses have also not been adequately defined . The two drugs were compared in 44 asthmatics in a double-blind , r and omized crossover , placebo-controlled study . There were four test days on which each patient received the following sequences of drugs : sal – sal – ipra , sal – sal – placebo , ipra – ipra – sal , and ipra – ipra – placebo .  Baseline forced expiratory volume in 1 sec(FEV1 ) was similar on the four days . The change in FEV1 produced by salbutamol when given as the first bronchodilator was 0.50 ± 0.30 L as compared to a change of 0.39 ± 0.27 L produced by ipratropium ( p < 0.01 ) . Both salbutamol and ipratropium result ed in statistically similar further improvements in FEV1 when given as the second drug . There was , however , a wide patient-to-patient variability in response , with some patients showing greater improvement with salbutamol and others with ipratropium .  Younger patients showed a greater response to salbutamol as compared to older patients , while no such difference was observed with ipratropium . Males responded better to both the drugs as compared to females . It was concluded that both salbutamol and ipratropium  are effective bronchodilators in asthma patients , although the overall response to salbutamol appears to be superior . However , some patients may respond better to one or other of the two drugs . Sequential administration of the two drugs may be a justified therapeutic approach as some patients show have further improvement with use of the second drug IK-6 , a combination of the sympathomimetic fenoterol ( low dose ) and the anticholinergic ipratropium bromide ( normal dose ) , was tested single-blind and cross-over in out patients with intrinsic asthma and in healthy volunteers . In 12 patients IK-6 result ed in a good acute bronchodilatation , the onset was as quick as following fenoterol and the maximum was as good as following ipratropium bromide . In another 12 patients the protective effect against an acetylcholine-induced bronchoconstriction was better after IK-6 than after ipratropium bromide and much better than after salbutamol . In these patients IK-6 caused no unwanted side effects . In 10 healthy volunteers the effect on heart rate was tested after inhalation of 20 puffs of bronchodilators applied by metered dose inhaler . The anticholinergics ( ipratropium bromide , oxitropium bromide , dibenzothiepine-derivative ) caused no effect . Following fenoterol a marked increase in heart rate could be observed , whereas the combination IK-6 caused only a slight increase Concern about side‐effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi‐medication regimen of severe asthmatics . We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti‐asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability . Five in‐ patients , 12–15 years old , completed a double‐blind , cross‐over trial of theophylline vs placebo . All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes . Regular medications consisted of long‐acting theophylline with levels between 12 mcg/ml and 16 mcg/ml , and prednisone 10–30 mg on alternate days . In addition , they were all taking inhaled metaproterenol , cromolyn sodium , atropine sulphate , and beclomethasone dipropionate four times daily ( qid ) . Patients received either theophylline or placebo during two drug periods . All other medications were unchanged . Parameters measured were symptom score , number of extra respiratory treatments ( prn RTs ) , increase in steroid dosage , and daily spirometry . During the placebo period , all five patients required increased steroids , daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection . A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all . These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who can not be controlled with all other available bronchodilators , cromolyn , and inhaled and systemic steroids Background . The National Asthma Education and Prevention Program ( NAEPP ) Expert Panel Report 3 guidelines advise the addition of ipratropium bromide to short-acting β-agonist therapy for the treatment of patients with severe acute asthma exacerbation . Methods . This was a prospect i ve , double-blind , r and omized , controlled study involving 141 adults , presenting to two EDs with acute severe asthma exacerbation . Patients were treated using a st and ardized pathway with levalbuterol plus ipratropium or levalbuterol alone . Primary outcomes were changes from baseline in the percentage of predicted forced expiratory volume in 1 second ( FEV1 ) at 30 minutes and 60 minutes after completion of treatment . Secondary outcomes included hospitalization and relapse rates . Occurrence of adverse events was recorded . Results . Sixty-seven patients in the levalbuterol plus ipratropium group and 74 patients in the levalbuterol group completed the study . Overall , there was no significant difference in the improvement in percent predicted FEV1 between the two groups at 30 minutes [ difference in change between study groups at 30 minutes : 1 % ( 95 % CI : ? 3 to 2 % ) or at 60 minutes : 3 % ( 95 % CI : 1–6 % ) ] No difference was noted in hospitalization rates between the treatment groups [ combination therapy group , 33 % ; single therapy group , 47 % , difference : −14 % ( 95 % CI : −30 to 20 % ) ] . Post-hoc analysis revealed that patients receiving ipratropium in addition to levalbuterol were 1.5 times more likely to experience side effects ( palpitations ) than patients treated with levalbuterol alone ( RR 1.5 ; 95 % CI : 1.2–1.9 ) No differences in relapse rates were noted between the groups . Post-hoc analysis revealed more side effects in patients receiving levalbuterol plus ipratropium . Conclusion . We were unable to demonstrate superiority of adding ipratropium to levalbuterol in alleviating obstruction as measured by FEV1 or in decreasing the need for hospitalization among adult patients presenting to the ED with acute severe asthma exacerbation Twelve patients admitted to hospital with an acute attack of bronchial asthma were studied . Six were treated initially with nebulized salbutamol solution by inhalation and 1 hour later by ipratropium bromide given in the same way ; the other six were treated first with ipratropium bromide and 1 hour later by salbutamol . Ipratropium bromide was shown to be as effective as salbutamol when used as the initial bronchodilator but salbutamol produced significant further improvement when given 1 hour after ipratropium The relationship between change in airway calibre and change in airway reactivity after administration of bronchodilator drugs has been investigated by comparing the effect of increasing doses of inhaled salbutamol and ipratropium bromide on the forced expiratory volume in one second ( FEV1 ) , specific airways conductance ( sGaw ) , and the dose of histamine causing a 20 % fall in FEV1 ( PD20 ) in six subjects with mild asthma . On each of 10 occasions measurements were made of baseline FEV1 , sGaw , and PD20 after 15 minutes ' rest , and followed one hour later , when the FEV1 had returned to baseline , by a single nebulised dose of salbutamol ( placebo , 5 , 30 , 200 and 1000 micrograms ) or ipratropium ( placebo , 5 , 30 , 200 and 1000 micrograms ) given in r and om order . Measurements of FEV1 , sGaw , and PD20 were repeated 15 minutes after salbutamol and 40 minutes after ipratropium . Salbutamol and ipratropium caused a similar dose related increase in FEV1 and sGaw , with a mean increase after the highest doses of 0.76 and 0.69 litres for FEV1 and 1.15 and 0.96 s-1 kPa-1 for sGaw . Salbutamol also caused a dose related increase in PD20 to a maximum of 2.87 ( 95 % confidence interval 2.18 - 3.55 ) doubling doses of histamine after the 1000 micrograms dose , but ipratropium bromide caused no significant change in PD20 ( maximum increase 0.24 doubling doses , 95 % confidence interval -0.73 to 1.22 ) . Thus bronchodilatation after salbutamol was associated with a significantly greater change in airway reactivity than a similar amount of bronchodilatation after ipratropium bromide . This study shows that the relation between change in airway reactivity and bronchodilatation is different for two drugs with different mechanisms of action , suggesting that change in airway calibre is not a major determinant of change in airway reactivity with bronchodilator drugs The aim of this study was to compare the bronchodilator response of patients with either stable asthma or stable chronic bronchitis to the acute administration of oxitropium bromide and a beta agonist ( fenoterol ) when given both separately and together in order to determine the responses of these two groups of patients and the optimal doses of these agents when given in combination . The responses of 23 patients with asthma and 25 patients with chronic bronchitis to 400 micrograms of fenoterol , and 200 micrograms of oxitropium given either alone or together with 100 , 200 or 400 micrograms of fenoterol was studied . The peak bronchodilator response to oxitropium bromide of the patients with chronic bronchitis was equivalent to the fenoterol response while , in the patients with asthma , the response to oxitropium bromide was approximately 30 % of the response to fenoterol . In both groups of subjects the addition of oxitropium bromide to fenoterol significantly increased both the magnitude and the duration of the bronchodilator response without a significant increase in side effects . In both groups of subjects 200 micrograms of oxitropium bromide and 200 micrograms or more of fenoterol gave the optimal response 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 To evaluate the role of inhaled ipratropium bromide in acute asthma , a double-blind study of 384 emergency department patients compared the effect of the combination of ipratropium and albuterol with that of albuterol alone .  Patients were r and omized to receive nebulizer treatments with either 2.5 mg of albuterol or 2.5 mg of albuterol mixed with 0.5 mg of ipratropium bromide at entry and at 45 min . Spirometry , vital signs , and oxygen saturation were measured before and at 45 and 90 min following the nebulizer treatments . Serum potassium levels were obtained at entry and 90 min . The two groups did not differ significantly in age ( mean + /- SD = 33.4 + /- 9.3 and 32.5 + /- 9.7 years for the albuterol and ipratropium group and the albuterol group , respectively ) , baseline  FEV1 ( mean + /- SD = 1.22 + /- 0.42 and 1.25 + /- 0.44 L respectively ) , or prior use of asthma medications . At 45 min , there were significantly more responders ( 15 % increase in FEV1 over baseline ) in the group receiving albuterol and ipratropium compared with albuterol and saline solution ( 85 % and 78 % , respectively ; p = 0.045 ) , but the median change in FEV1 from baseline did not differ ( 0.530 L for the albuterol and ipratropium group and 0.420 L for the albuterol and saline solution group ; p = 0.347 ) . By 90 min , the percentage of responders did not differ ( 88 % and 89 % , respectively ) , and the median change in FEV1 was 0.680 L for the group receiving albuterol and ipratropium and 0.650 L for the group receiving albuterol and saline solution ( p = 0.693 ) . There were no significant adverse events experienced by patients in either group . Furthermore , there were no significant differences in the number of patients requiring additional therapy in the emergency department or hospitalization . We conclude that in this population of inner city asthmatics , we were unable to demonstrate significant additive benefit of nebulized ipratropium bromide to nebulized albuterol The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction . Patients were assigned to one of three treatment regimens according to a r and omized schedule : 0.5 mg of ipratropium bromide , 1.25 mg of fenoterol hydrobromide , and 0.5 mg of ipratropium plus 1.25 mg of fenoterol . In 148 patients with acute exacerbations of asthma ( mean one-second forced expiratory volume , 1.18 + /- 0.64 liters ) , all three regimens produced significant improvement in one-second forced expiratory volume ( p less than 0.001 ) . The greatest improvement followed treatment with the  ipratropium-fenoterol combination ( 0.53 + /- 0.40 liters at 45 minutes ; 0.57 + /- 0.51 liters at 90 minutes ) and was significantly greater than that following either ipratropium alone ( p less than 0.001 ) or fenoterol alone ( p less than 0.05 ) . In 51 patients with acute exacerbations of chronic obstructive pulmonary disease ( mean one-second forced expiratory volume , 0.67 + /- 0.29 liter ) , each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes ( for all , p less than 0.05 ) , but there was no significant difference among the three treatment regimens . It is concluded that , in patients with acute asthma , combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone . In patients with acute exacerbations of chronic obstructive pulmonary disease , although either sympathomimetic or anticholinergic therapy provides bronchodilatation , no further benefit could be demonstrated from combination therapy Multiple studies have examined adding nebulized ipratropium bromide to intermittent albuterol for the treatment of acute asthma . Although continuous nebulized treatments in themselves offer benefits ; few data exist regarding the efficacy of adding ipratropium bromide to a continuous nebulized system . To compare continuous nebulized albuterol alone ( A ) vs. albuterol and ipratropium bromide ( AI ) in adult Emergency Department ( ED ) patients with acute asthma , a prospect i ve , r and omized , double-blind , controlled clinical trial was conducted on a convenience sample of patients ( IRB approved ) . The setting was an urban ED . Consenting patients > 18 years of age with peak expiratory flow rates ( PEFR ) < 70 % predicted , between October 15 and December 28 , 1999 , were r and omized  to albuterol ( 7.5 mg/h ) + ipratropium bromide ( 1.0 mg/h ) , or albuterol alone via continuous nebulization using the Hope Nebulizer ( B&B Technologies Inc. , Orangevale , CA ) for 2 h. Main outcome measures were changed in mean improvement at 60 and 120 min PEFR compared to baseline ( time 0 ) . Secondary measures were admission rates . Data were analyzed using appropriate parametric and non-parametric tests ( p < 0.05 statistically significant ) . Sixty-two patients ( 30 women ) completed enrollment : 32 in ( AI ) and ( 30 ) in ( A ) . Four ( A ) and 2 ( AI ) patients are without 120 min data : 3 ( A ) and 1 ( AI ) were discharged after 60 min , whereas one each ( A ) and ( AI ) worsened and were admitted before 120 min . There were no statistically significant differences between treatment groups in age , sex , predicted or initial PEFR .  Thirteen ( 19.4 % ) patients were admitted . There was no statistically significant difference in improvement of mean PEFR at 60 min or 120 min compared to baseline , between groups , using repeated measures analysis of variance . Mean improvement in PEFR at 60 min compared to baseline ( time 0 ) : ( A ) = 93.2 L/min ( 95 % confidence interval [ CI ] 64.5 - 121.8 ) , ( AI ) = 86.6 L/min ( 95 % CI 58.9 - 114.3 ) ; mean improvement in PEFR at 120 min compared to baseline ( time 0 ) ( A ) = 116.5 L/min ( 95 % CI 84.5 - 148.5 ) , ( AI ) = 126.4 L/min ( 95 % CI 95.4 - 157.4 ) . There was no statistically significant difference in admission rates between groups : 5/30 ( A ) and 8/32 ( AI ) ( p = 0.62 ) . There were no significant differences in mean improvement of PEFR at either 60 or 120 min between ED patients with acute asthma receiving continuous albuterol alone vs. those receiving albuterol in combination with ipratropium bromide The role of ipratropium bromide as adjunct therapy to beta-agonists in acute asthma is uncertain . We therefore decided to compare the use of 3 mg of salbutamol sulfate alone vs 3 mg salbutamol sulfate with 0.5 mg ipratropium bromide in patients with acute asthma . Patients presenting with acute asthma and an FEV1 less than 70 % predicted were r and omized to a single combination treatment vs salbutamol alone .  All patients received supplemental oxygen and methylpred-nisolone , 125 mg , IV . Baseline measurements were repeated at 45 and 90 min and these included spirometry , oximetry , and vital signs .  A total of 952 patients were screened of whom 342 patients were deemed eligible and were r and omized in two groups of 171 patients . The mean ( SE ) age was 30 years ( 0.9 ) vs 29 years ( 0.7 ) , women , 103 ( 60.2 % ) vs 110 ( 64 % ) , 81 ( 47.4 % ) never-smoked vs 83 ( 48.5 % ) , and duration of asthma in years 16.0 ( 0.8 ) vs 16.6 ( 0.8 ) were no different in the combination vs salbutamol alone group , respectively . Likewise , there was no significant difference in asthma therapy received in the 24 h prior to presentation ; most notably , 151 ( 88.3 % ) vs 153 ( 89.5 % ) received inhaled beta-agonists in that period . Baseline FEV1 was 1.62 L ( 0.05 L ) vs 1.53 L ( 0.03 L ) , and median time to treatment being received was no different between both groups . Both treatment arms improved significantly . The increase in FEV1 in the combination group was 0.6I L ( 0.04 L ) and in the salbutamol alone group was 0.52 L ( 0.04 L ) at 90 min . There was a trend toward greater bronchodilation in the combination group , but this did not reach statistical significance . Fewer hospitalizations , 5.9 % vs 11.2 % , occurred in the combination group , but this did not reach statistical significance . In conclusion , this large multicenter study failed to show a significantly better response to a combination of salbutamol and ipratropium bromide vs salbutamol alone OBJECTIVE To determine the efficacy of combination therapy using atropine sulfate and albuterol in the treatment for an acute exacerbation of asthma . METHODS A prospect i ve , r and omized double-blind , placebo-controlled study was performed in the ED of a large , inner-city , university-affiliated teaching hospital . Participants were a convenience sample of patients presenting to the ED between September 1993 and March 1994 with acute exacerbations of their asthma . Patients judged to be in extremis were excluded . All patients received 3 nebulized treatments with 2.5 mg of albuterol at 0 , 30 , and 60 minutes . Patients were r and omized into 1 of 3 groups with the following added to their nebulizer solutions : 1 ) saline placebo during all 3 treatments ; 2 ) 2.0 mg atropine sulfate added to the first nebulizer and saline in the second and third ; or 3 ) 2.0 mg atropine to the first and third treatments ( with saline in the second ) . No other medication was administered during the study period . At 90 minutes , the patients were evaluated for admission or release from the ED according to predetermined criteria , and additional medications were given as necessary . Vital signs , peak expiratory flow rate ( PEFR ) , degree of wheezing , level of distress , and side effects were measured before and after each nebulizer treatment . RESULTS Of the 153 patients eligible for the study , 126 completed the entire study protocol . There was no significant difference between the 3 groups on any parameter studied , including improvement of PEFR , vital signs , or level of distress . There was no difference in the admission rate between the 3 groups , nor was there a difference in the incidence of side effects among the groups . CONCLUSION In this study population , combination therapy with atropine sulfate and albuterol offered no significant benefit over the use of albuterol alone in the treatment for acute exacerbation of asthma 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 . Nebulization treatment of acute asthma with terbutaline and ipratropium bromide , given either separately with a 30-minute interval or combined as single inhalation , was compared with injection treatment with a combination of terbutaline given subcutaneously and theophylline given intravenously . Seventy-seven episodes of acute asthma were studied . Nebulization treatment gave the same degree of bronchodilation as the injections , both immediately after treatment [ measured as increase in forced expiratory volume in 1 second ( FEV1 ) in peak expiratory flow rate ( PEFR ) and improvement of dyspnoea ] and during the following 6 days ( measured by PEFR recordings at home ) . The injection treatment caused a moderate increase in heart rate , whereas no circulatory side-effects were noted during nebulization treatment . Administration of ipratropium bromide 30 minutes after terbutaline was not more effective than the combination of both substances as a single nebulization In a double-blind r and omized trial , 40 patients with acute severe asthma were given either nebulized salbutamol , 5 mg , or salbutamol , 5 mg mixed with ipratropium bromide 500 micrograms , on admission to hospital and again two hours later . There was no significant difference between the mean peak flows of the two treatment groups at any time . However , two hours after each treatment , there were fewer subjects in the ipratropium and salbutamol group whose peak flow rates had fallen back toward baseline levels than in the salbutamol only treatment group . Thus , although ipratropium did not improve the overall maximal bronchodilator response , it may have prolonged the duration of the response , which would be a clinical ly useful effect STUDY OBJECTIVE Corticosteroids are thought to exert their physiologic effects in asthma over the course of several hours . In this study we tested the hypothesis that intravenous methylprednisolone improves airflow in a shorter time frame ( 2 hours ) in adults with acute asthma . METHODS In a r and omized , double-blind , placebo-controlled trial , 56 adult asthmatic patients with peak expiratory flow rates ( PEFRs ) less than 50 % predicted after an initial albuterol aerosol treatment were studied . These patients were r and omly assigned to treatment with either 125 mg of intravenous methylprednisolone or an equivalent volume of normal saline solution ( placebo ) . Patients were also treated with identical schedules of nebulized ipratropium and albuterol .  Patients were recruited from an emergency department at an urban academic medical center . The primary endpoints were changes in PEFR and in percent predicted PEFR over time . PEFRs were assessed at baseline and at 1 and 2 hours . Heart rate changes over time and the proportion of admissions in the 2 groups were also compared . RESULTS The increases in PEFR and percent predicted PEFR over time were both significantly greater in the methylprednisolone treatment group ( P = . 002 and P = .005 , respectively ) . The increases in geometric mean peak flow at 60 and 120 minutes were 79 and 96 L/min for the methylprednisolone group and 54 and 68 L/min for the placebo group . There was also a significantly different change in heart rates with time between the methylprednisolone and placebo groups ( P = .029 ) , with the placebo group showing a moderate increase in heart rate over time . Although the proportion of patients admitted for status asthmaticus was less in the methylprednisolone treatment group ( 8/30 ) compared with the placebo group ( 10/26 ) , this difference in proportions ( -.118 , 95 % confidence interval -.363 to.127 ) was not significant . CONCLUSION These data suggest that use of corticosteroids should be considered relatively early in the treatment of patients with acute asthma in whom initial bronchodilator therapy fails to produce an adequate response 34 patients with acute asthmatic attack were studied in double-blind , r and omized and crossover manner . Each of them was treated with following two protocol s during two sequential days : 0.5 mg of ipratropium bromide ( IPB ) , followed by 5 mg of salbutamol sulfate ( SAS ) 75 minutes later ; or 5 mg of SAS , followed by another dose 35 minutes late . The drugs were delivered via a jet nebulizer . The effects and side-effects of the treatment were evaluated immediately before the first inhalation and at peak of bronchodilatation ( 60 - 75 minutes after IPB or 20 - 35 minutes after SAS ) . Compared with inhaled SAS , IPB produced considerable improvement in central airway parameters such as forced expiratory volume in one second ( FEV1 ) peak expiratory flow ( PEF ) and respiratory resistance ( Rrs ) ( P greater than 0.05 ) , but less improvement in peripheral airway parameters such as forced vital capacity ( FVC ) and maximal mid-expiratory flow ( MMEF ) ( P less than 0.01 ) . The sequential inhaled SAS after IPB improved all five parameters ( P less than 0.01 ) , but the repeated dose of SAS increased only MMEF ( P less than 0.01 ) . Compared with double-dose SAS , the sequential treatment with IPB and SAS 1 ed to considerable improvement in FVC and MMEF ( P greater than 0.05 ) , but greater improvement in FEV1 , PEF and Rrs ( P less than 0.01 ) . Heart ( rate and tremor scores after two doses of SAS increased significantly ( P less than 0.01 ) . It is concluded that IPB alone is less effective than beta-adrenoceptor agonist , but its combination with SAS would be an effective and safe treatment in acute asthmatic attack We design ed a larger , double-blind , r and omized , prospect i ve trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide ( IB ) and beta(2)-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given beta(2)-agonists alone . One hundred eighty patients ( mean age + /- SD , 34.3 + /- 10.5 yr ) who presented to an emergency department ( ED ) for treatment of an exacerbation of asthma ( baseline FEV(1 ) < 50 % of predicted ) were assigned in a r and omized , double-blind fashion to receive albuterol and placebo ( n = 92 ) or albuterol and IB ( n = 88 ) . Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h ( 24 puffs or 2,880 microg of albuterol and 504 microg of IB each hour ) . Primary outcome measures were improvement in pulmonary function ( FEV(1 ) or peak expiratory flow [ PEF ] ) , and hospital admission rates . In both groups , pulmonary function improved significantly over baseline values ( p < 0.01 ) . Subjects who received IB had an overall 20.5 % ( 95 % CI : 2.6 to 38.4 % ) ( p = 0.02 ) greater improvement in PEF and a 48.1 % ( 95 % CI : 19.8 to 76.4 % ) ( p = 0.001 ) greater improvement in FEV(1 ) from the control group . At the end of protocol ( 3 h ) , 39 % ( n = 36 ) of patients in the control group and 20 % ( n = 18 ) in the IB group were admitted ( p = 0.01 ) . The use of high doses of IB reduced the risk of hospital admission 49 % ( relative risk = 0.51 , 95 % CI : 0.31 to 0.83 ) . Five ( 95 % CI : 3 to 17 ) patients would need to be treated with high doses of IB to prevent a single admission . Kaplan-Meier-estimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment , showed a significant difference in favor of the IB group ( log-rank test = 0.005 ) . A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction ( FEV(1 ) < /= 30 % of predicted ) and long duration of symptoms before the ED presentation ( > /= 24 h ) . On the contrary , previous use of inhaled beta(2)-agonists did not modify the admission rate and the pulmonary function response to IB . In conclusion , our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer , particularly in patients with FEV(1 ) less than 30 % , and with long duration of symptoms before the ED presentation ( > /= 24 h ) The aim of this study was to investigate the effects of nebulized ipratropium in patients with acute asthma in order to determine whether it augments the bronchodilator effect of a beta agonist drug . A total of 28 patients with acute asthma were r and omly allocated to treatment every six hours with either 1 mg nebulized fenoterol ( group A ) or 1 mg fenoterol and 0.5 mg ipratropium ( group B ) . There was no significant difference between the mean FEV1 of the two groups prior to treatment and increasing the dose of fenoterol from 1 mg to 2 mg did not increase the response . However the mean change in FEV1 after 48 hours ( expressed as a percentage of the predicted maximal response ) was 40.1 + /- 7.2 percent in group A and 54.3 + /- 9.2 percent in group B ( p less than 0.005 ) . It was concluded that the response of patients with acute asthma to fenoterol was significantly enhanced by the addition of the anticholinergic agent ipratropium bromide STUDY OBJECTIVE Recent reports suggest that glycopyrrolate is as effective as metaproterenol in the treatment of acute bronchospasm . The purpose of this study was to investigate whether the addition of a single aerosolized dose of glycopyrrolate to an albuterol regimen results in a greater improvement in pulmonary function than treatment with an albuterol regimen alone in patients with acute asthma . DESIGN Prospect i ve , r and omized , double-blinded , controlled study . All patients received a total of three aerosol treatments and 60 mg solumedrol IV push . Patients were r and omized to receive 2 mg aerosolized glycopyrrolate ( combination therapy ) or aerosolized placebo ( control ) in addition to their first 2.5 mg albuterol aerosol treatment . Both groups received 2.5 mg aerosolized albuterol alone for the next two treatments . SETTING An urban teaching hospital emergency department . PARTICIPANTS One hundred twenty-five patients with acute exacerbation of asthma were entered into the study . MAIN RESULTS There was no difference in pretreatment forced expiratory volume ( one second ) ( FEV1 ) between the control group and the glycopyrrolate group . Asthmatic patients receiving combination therapy had less of a change in FEV1 ( 52 % ) than did control patients ( 82 % , P < .05 ) . CONCLUSION The combination of glycopyrrolate and albuterol does not appear to be beneficial over albuterol alone in treating patients with acute exacerbation of asthma 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 The efficacy and safety of a novel fenoterol/ipratropium bromide metered-dose inhaler ( MDI ) formulated with a non-chlorinated propellant , HFA134a , has been compared with placebo and the conventional chlorofluorocarbon (CFC)-containing fenoterol/ipratropium bromide inhaler ( Berodual ) in asthmatic patients . Fifty-two patients were enrolled in two centres . The fenoterol/ ipratropium bromide treatment produced significantly ( P < 0.0001 ) greater bronchodilatation than placebo . There were no significant differences between the mean peak and average forced expiratory volume in the first second ( FEV1 ) for patients receiving 2 puffs of the fenoterol/ipratropium bromide HFA134a inhaler and the conventional CFC inhaler . In addition , time to onset and duration of efficacy were comparable for these two treatments . None of the patients showed a fall of > or = 15 % in baseline FEV1 or needed rescue medication within 30 min after inhalation of the test drug . No paradoxical bronchoconstriction was observed as measured by sGaw . The two inhaler formulations were well tolerated . A taste-related complaint , lasting for a few minutes after inhalation , was reported by a higher proportion of patients who inhaled the HFA134a formulation , mainly by patients selected in one of the two centres . In conclusion , a dose of 100 micrograms fenoterol/40 micrograms ipratropium bromide inhaled from a MDI containing HFA134a propellant is safe and provides effective bronchodilatation of equivalent degree , onset and duration of action to the same dose from the conventional CFC formulation
BACKGROUND Inhaled short-acting anticholinergics ( SAAC ) and short-acting beta₂-agonists ( SABA ) are effective therapies for adult patients with acute asthma who present to the emergency department ( ED ) .
It is unclear , however , whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone .
OBJECTIVES To conduct an up-to- date systematic search and meta- analysis on the effectiveness of combined inhaled therapy ( SAAC + SABA agents ) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma .