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Inhaled magnesium sulfate in the treatment of acute asthma.
Powell, C, Dwan, K, Milan, SJ, Beasley, R, Hughes, R, Knopp-Sihota, JA, Rowe, BH
The Cochrane database of systematic reviews. 2012;:CD003898
Abstract
BACKGROUND Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO(4)) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO(4) has been demonstrated, little is known of the role of inhaled MgSO(4). OBJECTIVES To determine the efficacy of inhaled MgSO(4) administered in acute asthma on pulmonary functions and admission rates. SPECIFIC AIMS To quantify the effects of inhaled MgSO(4) i) in addition to inhaled β(2)-agonist, ii) in comparison to inhaled β(2)-agonist alone or iii) in addition to combination treatment with inhaled β(2) -agonist and ipratropium bromide. SEARCH METHODS Randomised controlled trials were identified from the Cochrane Airways Group register of trials in September 2012. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the grey literature and conference proceedings. SELECTION CRITERIA Randomised (or pseudo-randomised) controlled trials including adults or children with acute asthma were eligible for inclusion in the review. Studies were included if patients were treated with nebulised MgSO(4) alone or in combination with β(2)-agonist and/or ipratropium bromide and were compared with β(2)-agonist alone or inactive control. DATA COLLECTION AND ANALYSIS Trial selection, data extraction and risk of bias were assessed independently by two review authors. Efforts were made to collect missing data from authors. Results are presented as standardised mean differences (SMD) for pulmonary function and risk ratios (RR) for hospital admission; both are displayed with their 95% confidence intervals (CI). MAIN RESULTS Sixteen trials (21 references) of unclear and high risk of bias were eligible and included 896 patients who were randomised (838 patients completed). Seven of the 16 included studies involved adults exclusively, three included adults and paediatric patients, four studies enrolled paediatric patients and in the remaining two studies the age of participants was not stated.The design, definitions, intervention and outcomes were different in all 16 studies; this heterogeneity made direct comparisons difficult (see additional tables 1-3).The overall risk of bias among the included studies was variable and this is reflected in the 'Summary of findings' table with most outcomes being judged as only moderate or less.Inhaled magnesium sulfate in addition to inhaled β(2)-agonistThere was no statistically significant improvement in pulmonary function when inhaled MgSO(4) and β(2)-agonist was compared with β(2)-agonist alone (SMD 0.23; 95% CI -0.27 to 0.74; three studies, n = 188); however, there was considerable between study heterogeneity. There was no clear advantage in terms of hospital admissions (RR 0.76 95% CI 0.49, 1.16; four studies, n = 249), and there were no serious adverse events reported.Inhaled magnesium sulfate versus inhaled β(2)-agonistThe results of pulmonary function in three studies that compared inhaled MgSO(4) versus β(2)-agonist were too heterogeneous to combine; however, two of the studies found poorer lung function on MgSO(4). There was no significant difference in terms of hospital admissions in a single small study when MgSO(4) was compared to β(2)-agonist (RR 0.53 95% CI 0.05, 5.31; one study, n = 33), and there were no serious adverse events reported.Inhaled magnesium sulfate in addition to inhaled β(2)-agonist and ipratropiumA further comparison has been included in the 2012 update of this review of MgSO(4) given in addition to inhaled ipratropium and β(2)-agonist therapy (as recommended by the GINA guidelines). However, there is not yet enough data for this outcome to come to any definite conclusions, but both small studies in adults with severe asthma exacerbation found improvements in pulmonary function with additional inhaled MgSO(4). AUTHORS' CONCLUSIONS There is currently no good evidence that inhaled MgSO(4) can be used as a substitute for inhaled β(2)-agonists. When used in addition to inhaled β(2)-agonists (with or without inhaled ipratropium), there is currently no overall clear evidence of improved pulmonary function or reduced hospital admissions. However, individual study results from three trials suggest possible improved pulmonary function in those with severe asthma exacerbations (FEV1 less than 50% predicted). Heterogeneity among trials included in this review precludes a more definitive conclusion. Further studies should focus on inhaled MgSO(4) in addition to the current guideline treatment for acute asthma (inhaled β(2) -agonist and ipratropium bromide). As the evidence suggests that the most effective role of nebulised MgSO(4) may be in those with severe acute features and this is where future research should be focused. A set of core outcomes needs to be agreed upon both in adult and paediatric studies to allow improved study comparison in future.
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Polymorphism of the ADRB2 gene and response to inhaled beta- agonists in children with asthma: a meta-analysis.
Finkelstein, Y, Bournissen, FG, Hutson, JR, Shannon, M
The Journal of asthma : official journal of the Association for the Care of Asthma. 2009;(9):900-5
Abstract
BACKGROUND About 9% of children have asthma, corresponding to almost 6.8 million children in the USA and 1.1 million in the UK. Asthma exacerbations are the leading cause of pediatric emergency room visits and impose a large burden on the individual, family, and society. There is mounting evidence that therapeutic failure of inhaled beta-agonists is associated with polymorphisms of the beta(2)-adrenergic receptor gene (ADRB2); specifically, mutations leading to amino acid changes at positions 16 and 27, which alter down-regulation of the beta(2)-adrenergic receptor (beta(2)AR), induce resistance to the smooth-muscle relaxing effect of beta(2)-adrenergic agonists. METHODS We conducted a meta-analysis to examine the association between ADRB2 polymorphisms and the response to inhaled beta(2)-adrenergic agonists in children with asthma. We included all published studies until November 2008, in which asthmatic children underwent testing for acute bronchodilator response, defined as > or = 15% improvement in forced expiratory volume in 1 second (FEV(1)) and single nucleotide polymorphism (SNP) genotyping for positions 16 and/or 27 of the beta(2)AR. Individual and summary odds ratios were calculated using a random effects model. RESULTS We identified three case-control or family-based studies involving 960 asthmatic children (692 children with negative beta(2)-bronchodilator response, defined as < 15% improvement in FEV(1) and 268 children with positive bronchodilator response). We found a significant association between favorable therapeutic response to inhaled beta(2)-adrenergic agonists in asthmatic children and the Arg/Arg phenotype at position 16 of the beta(2)AR [OR = 1.77; 95% CI (1.01; 3.1); p = 0.029], compared with the Arg/Gly or Gly/Gly phenotypes. The beneficial effect of Arg at position 16 of the beta(2)AR was most pronounced in African-American asthmatic children [OR = 3.54; 95% CI (1.37, 9.13)]. There was no association between clinical response to beta(2)-agonists and polymorphism at amino acid position 27 of the beta(2)AR (OR = 1.04; 95% CI [0.76,1.42]). CONCLUSIONS Failure of bronchodilator response to inhaled beta-agonists in asthmatic children is associated with the Gly allele (Arg/Gly and Gly/Gly genotypes) at position 16 of the beta(2)-adrenergic receptor. Genetic typing for beta(2)AR polymorphism may help identify children with drug-resistant asthma.
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[Comparison of different vehicles for nebulized salbutamol in treatment of bronchial asthma exacerbations: a Meta-analysis].
Lu, XY, Zhou, JY
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences. 2006;(3):336-41
Abstract
OBJECTIVE To assess the efficacy of two vehicles for nebulized salbutamol in treatment of asthma exacerbations with Meta-analysis. METHODS All relevant randomized controlled clinical trials (RCT) with isotonic magnesium sulphate and saline as vehicles for inhaled salbutamol in treatment of asthma exacerbations were searched. A Meta-analysis was performed to evaluate the results of the two therapies. RESULT Five relevant RCTs from literature were collected and total 219 cases were included for analysis. The meta-analysis indicated that the significant improvements were obtained from isotonic magnesium sulphate as a vehicle for nebulized salbutamol, in comparison with saline [pooled standardized mean difference (SMD)=0.55(95% CI 0.28 - 0.83), P <0.001]. By further subgroup analysis, this change was properly significant in the subgroup of severe patients with their baseline FEV1% <30% [FEV1 weighted mean difference (WMD)=0.72 L(95% CI 0.30 L - 1.14 L), P <0.01]. The pooled results of vital signs between two vehicles did not demonstrate statistical significance. Overall, the risk of admission to hospital was not statistically reduced in patients using magnesium sulphate, who presented to the emergency department with an asthma exacerbation [pooled RR=0.64(95% CI 0.38 - 1.08), P >0.05]. CONCLUSION Compared with saline,the use of isotonic magnesium sulfate as an adjuvant to nebulize salbutamol is a beneficial therapy with improving spirometric airway function in the severe asthma exacerbation.
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Inhaled magnesium sulfate in the treatment of acute asthma.
Blitz, M, Blitz, S, Beasely, R, Diner, BM, Hughes, R, Knopp, JA, Rowe, BH
The Cochrane database of systematic reviews. 2005;(3):CD003898
Abstract
BACKGROUND Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO4) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO4 has been demonstrated, little is known about inhaled MgSO4. OBJECTIVES To examine the efficacy of inhaled MgSO4 in the treatment asthma exacerbations. SEARCH STRATEGY Randomised controlled trials were identified from the Cochrane Airways Group "Asthma and Wheez*" register. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the gray literature and conference proceedings. SELECTION CRITERIA Randomised (or pseudo-randomised) controlled trials were eligible for inclusion. Studies were included if patients were treated with nebulised MgSO4 alone or in combination with beta(2)-agonist and where compared to beta2-agonist alone or inactive control. DATA COLLECTION AND ANALYSIS Trial selection, data extraction and methodological quality were assessed by two independent reviewers. Efforts were made to collect missing data from authors. Results from fixed effects models are presented as standardized mean differences (SMD) for pulmonary functions and relative risks (RR) for hospital admission; both are displayed with their 95% confidence intervals (95% CI). MAIN RESULTS Six trials involving 296 patients were included. Four studies compared nebulised MgSO4 with beta2-agonist to beta2-agonist and two studies compared MgSO4 to beta2-agonist alone. Three studies enrolled only adults and 2 enrolled exclusively pediatric patients; three of the studies enrolled severe asthmatics. Overall, there was a significant difference in pulmonary function between patients whose treatments included nebulised MgSO4 in addition to beta2-agonist (SMD: 0.30; 95% CI: 0.03 to 0.56; 4 studies); however, hospitalizations were similar between the groups (RR: 0.69; 95% CI: 0.42 to 1.12; 3 studies). Subgroup analyses did not demonstrate significant differences in lung function improvement between adults and children, but were significantly different between severe and mild to moderate asthmatics (SMD: 0.69; 95% CI 0.13 to 1.25). Conclusions regarding treatment with nebulised MgSO4 alone are difficult to draw due to lack of studies in this area. AUTHORS' CONCLUSIONS Nebulised inhaled magnesium sulfate in addition to beta2-agonist in the treatment of an acute asthma exacerbation, appears to have benefits with respect to improved pulmonary function and there is a trend towards benefit in hospital admission. The benefit is significantly greater in more severe asthma exacerbations. Heterogeneity between trials included in this review precludes a more definitive conclusion.
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Inhaled magnesium sulfate in the treatment of acute asthma.
Blitz, M, Blitz, S, Beasely, R, Diner, BM, Hughes, R, Knopp, JA, Rowe, BH
The Cochrane database of systematic reviews. 2005;(4):CD003898
Abstract
BACKGROUND Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO4) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO4 has been demonstrated, little is known about inhaled MgSO4. OBJECTIVES To examine the efficacy of inhaled MgSO4 in the treatment asthma exacerbations. SEARCH STRATEGY Randomised controlled trials were identified from the Cochrane Airways Group "Asthma and Wheez*" register. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the gray literature and conference proceedings. SELECTION CRITERIA Randomised (or pseudo-randomised) controlled trials were eligible for inclusion. Studies were included if patients were treated with nebulised MgSO4 alone or in combination with beta2-agonist and where compared to beta2-agonist alone or inactive control. DATA COLLECTION AND ANALYSIS Trial selection, data extraction and methodological quality were assessed by two independent reviewers. Efforts were made to collect missing data from authors. Results from fixed effects models are presented as standardized mean differences (SMD) for pulmonary functions and relative risks (RR) for hospital admission; both are displayed with their 95% confidence intervals (95% CI). MAIN RESULTS Six trials involving 296 patients were included. Four studies compared nebulised MgSO4 with beta2-agonist to beta2-agonist and two studies compared MgSO4 to beta2-agonist alone. Three studies enrolled only adults and 2 enrolled exclusively pediatric patients; three of the studies enrolled severe asthmatics. Overall, there was a non significant improvement in pulmonary function between patients whose treatments included nebulised MgSO4 in addition to beta2-agonist (SMD: 0.23; 95% CI: -0.03 to 0.50; 4 studies). Hospitalizations were similar between the groups (RR: 0.69; 95% CI: 0.42 to 1.12; 3 studies). Subgroup analyses did not demonstrate significant differences in lung function improvement between adults and children, but in severe asthmatics the lung function difference was significant (SMD: 0.55; 95% CI: 0.12 to 0.98). Conclusions regarding treatment with nebulised MgSO4 alone are difficult to draw due to lack of studies in this area. AUTHORS' CONCLUSIONS Nebulised inhaled magnesium sulfate in addition to beta2-agonist in the treatment of an acute asthma exacerbation, appears to have benefits with respect to improved pulmonary function in patients with severe asthma and there is a trend towards benefit in hospital admission. Heterogeneity between trials included in this review precludes a more definitive conclusion.
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Inhaled magnesium sulfate in the treatment of acute asthma.
Blitz, M, Blitz, S, Beasely, R, Diner, BM, Hughes, R, Knopp, JA, Rowe, BH
The Cochrane database of systematic reviews. 2005;(2):CD003898
Abstract
BACKGROUND Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO4) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO4 has been demonstrated, little is known about inhaled MgSO4. OBJECTIVES To examine the efficacy of inhaled MgSO4 in the treatment asthma exacerbations. SEARCH STRATEGY Randomised controlled trials were identified from the Cochrane Airways Group "Asthma and Wheez*" register. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the gray literature and conference proceedings. SELECTION CRITERIA Randomised (or pseudo-randomised) controlled trials were eligible for inclusion. Studies were included if patients were treated with nebulised MgSO4 alone or in combination with beta2-agonist and where compared to beta2-agonist alone or inactive control. DATA COLLECTION AND ANALYSIS Trial selection, data extraction and methodological quality were assessed by two independent reviewers. Efforts were made to collect missing data from authors. Results from fixed effects models are presented as standardized mean differences (SMD) for pulmonary functions and relative risks (RR) for hospital admission; both are displayed with their 95% confidence intervals (95% CI). MAIN RESULTS Six trials involving 296 patients were included. Four studies compared nebulised MgSO4 with beta2-agonist to beta2-agonist and two studies compared MgSO4 to beta2-agonist alone. Three studies enrolled only adults and 2 enrolled exclusively pediatric patients; three of the studies enrolled severe asthmatics. Overall, there was a significant difference in pulmonary function between patients whose treatments included nebulised MgSO4 in addition to beta2-agonist (SMD: 0.37; 95% CI: 0.1 to 0.63; 4 studies); however, hospitalizations were similar between the groups (RR: 0.64; 95% CI: 0.40 to 1.04; 3 studies). Subgroup analyses did not demonstrate significant differences in lung function improvement between adults and children, or between severe and mild to moderate asthmatics. Conclusions regarding treatment with nebulised MgSO4 alone are difficult to draw due to lack of studies in this area. AUTHORS' CONCLUSIONS Nebulised inhaled magnesium sulfate in addition to beta2-agonist in the treatment of an acute asthma exacerbation, appears to have benefits with respect to improved pulmonary function and there is a trend towards benefit in hospital admission. Heterogeneity between trials included in this review precludes a more definitive conclusion.
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Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction.
Spooner, CH, Spooner, GR, Rowe, BH
The Cochrane database of systematic reviews. 2003;(4):CD002307
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Abstract
BACKGROUND Exercise-induced bronchoconstriction (or asthma) following strenuous physical exertion is common and can cause sub-optimal performance, symptoms such as cough, dyspnea, wheeze, chest tightness, and can lead people to avoid physical activity. Management focuses on prevention with pre-exercise treatment using various pharmacologic agents. Mast cell stabilizing agents are effective in attenuating exercise-induced bronchoconstriction but their effectiveness compared to bronchodilator agents is unclear. OBJECTIVES To quantitatively compare the effects of inhaling a single dose of either mast cell stabiliser - nedocromil sodium or sodium cromoglycate - to a single dose of short acting beta-agonists or anti-cholinergic agents - atropine or ipratropium bromide - prior to a strenuous exercise challenge in participants with asthma who are at least 6 years of age and suffer from reproducible exercise-induced bronchoconstriction. The review also compares the effects between a short acting beta-agonist alone to a combination of a short acting beta-agonist + mast cell stabiliser. SEARCH STRATEGY We searched the Cochrane Airways Group ASTHMA and WHEEZ* trials register, Cochrane CENTRAL, Current Contents, review articles, textbooks and reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. SELECTION CRITERIA Randomised trials comparing a single prophylactic dose of a mast cell stabiliser to a short acting beta-agonist, anti-cholinergic agent, or a short acting beta-agonist alone to a combination of short acting beta-agonist plus a mast cell stabiliser to prevent exercise-induced bronchoconstriction in asthmatics over six years old. The exercise challenge had to conform to acceptable standards and pulmonary function (PFT) reported as percent decrease from baseline of FEV1 or peak flow. Complete protection (maximum % fall PFT <15% post-exercise) and clinical protection (50% improvement over placebo effect) measures were included. DATA COLLECTION AND ANALYSIS Trial inclusion and quality assessments were conducted independently by two reviewers using standardised forms. A second reviewer confirmed data extraction and calculations. Attempts were made to contact study authors. The pooled estimate involving continuous pulmonary function measures are reported as a weighted mean difference (WMD), dichotomous data as an odds ratio (OR), both with 95% confidence intervals (95%CI) using a random effects model. Heterogeneity tests for pooled results were performed. MAIN RESULTS Twenty-four trials (518 participants) conducted in 13 countries between 1976 and 1998 were included. All drugs were effective at attenuating the exercise-induced bronchoconstriction response but to varying degrees even within the same individual. Compared to anti-cholinergic agents, mast cell stabilisers were somewhat more effective at attenuating bronchoconstriction. On average the maximum fall on MCS was reduced to 7.1% compared to 13.8% on AC ( WMD = 6.7%; 95% CI: 3.3 to 10.0), provided more individuals with complete protection (73% vs 56%; OR = 2.2; 95% CI: 1.3 to 3.7) and clinical protection (73% vs 52%; OR = 2.7; 95% CI: 1.1 to 6.4). There were no subgroup differences based on age, severity, or study quality, and no adverse effects were reported for either agent group. When compared to short acting beta-agonists mast cell stabilisers were not as effective at preventing deterioration. On average the maximum fall on MCS was 11.2% compared to 4.3% on beta agonists ( WMD = 6.8%; 95% CI: 4.5 to 9.2). MCS provided fewer individuals with complete protection (66% vs 85%; OR = 0.3; 95% CI: 0.2 to 0.5) or clinical protection (55% vs 77%; OR = 0.4; 95% CI: 0.2 to 0.8). There were no significant subgroup differences based on age, severity, drug, delivery, or study quality. A non-significant difference in side effects was demonstrated with 11% of short acting beta-agonist patients experiencing side effects compared to 3% of those receiving mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining masta-agonist patients experiencing side effects compared to 3% of those receiving mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining mast cell stabilisers with a short acting beta-agonist did not produce significant advantages to pulmonary function over short acting beta-agonists alone. On average the maximum fall on SABA only was reduced to 5.3% compared to 3.5% on the combination ( WMD = 1.8%; 95% CI: -1.1 to 4.6). Beta-agonists alone provided fewer individuals with complete protection (68% vs 80%; OR = 0.5; 95% CI: 0.2 to 1.4) or clinical protection (70% vs 86%; OR=0.4; 95% CI: 0.1 to 1.2) but the difference did not reach significance (p=0.17). There were no subgroup differences. REVIEWER'S CONCLUSIONS In a population of stable asthmatics short acting beta-agonists, mast cell stabilisers, or anticholinergics will provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects. On average, SABAs resulted in more effective attenuation than mast cell stabilisers, while mast cell stabilisers were more effective than anti-cholinergic agents. Combining SABA and mast cell stabilisers may be appropriate in selected cases. The variability in the individual degree of response to these drugs in multi arm trials suggests clinicians and patients work together to identify the most effective prophylactic therapy.
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Continuous versus intermittent beta-agonists in the treatment of acute asthma.
Camargo, CA, Spooner, CH, Rowe, BH
The Cochrane database of systematic reviews. 2003;(4):CD001115
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Abstract
BACKGROUND Patients with acute asthma treated in the emergency department are frequently treated with intermittent inhaled beta-agonists delivered by nebulisation. The use of continuous beta-agonist (CBA) via nebulisation in the emergency setting may offer additional benefits in acute asthma. OBJECTIVES To determine the efficacy (e.g., reductions in admission, improvement in pulmonary functions) and risks (e.g., adverse events, effects on vital signs) of continuous versus intermittent inhaled beta-agonists for the treatment of patients with acute asthma managed in the emergency department. SEARCH STRATEGY Randomised controlled trials were identified from the Cochrane Airways Review Group "Asthma and WHEEZ*" Register which is a compilation of systematic searches of CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched. The search is considered updated to June 2003. SELECTION CRITERIA Only randomised controlled trials (RCTs) were eligible for inclusion. Studies were included if patients presented with acute asthma and were treated with either continuous or intermittent inhaled beta-agonists early in the ED treatment. "Continuous" nebulisation was defined as truly continuous aerosol delivery of beta-agonist medication (e.g., using a commercially available large-volume nebuliser, or a small-volume nebuliser with infusion pump) or sufficiently frequent nebulisations that medication delivery was effectively continuous (i.e., 1 nebulisation every 15 minutes or > 4 nebulisations per hour). Studies also needed to report either pulmonary function or admission results. Two reviewers independently selected potentially relevant articles and two additional reviewers independently selected articles for inclusion. Methodological quality was independently assessed by two reviewers. DATA COLLECTION AND ANALYSIS Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager (Version 4.1). Relative risks (RR), weighted mean differences (WMD) and standardized mean differences (SMD) are reported with corresponding 95% confidence intervals (CI); both peak expiratory flow rates (PEFR) and forced expiratory volume in one second (FEV-1) data are reported. MAIN RESULTS 165 trials were reviewed and eight were included; a total of 461 patients have been studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission to hospital was reduced with CBA compared to intermittent beta-agonists (RR: 0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI: 0.5 to 0.9). Patients receiving CBA demonstrated small but statistically significant improvements in pulmonary function tests when all studies were pooled. Patients receiving CBA had greater improvements in % predicted FEV-1 (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this effect was observed by 2-3 hours. Continuous treatment was generally well tolerated, with no clinically important differences observed in pulse rate (WMD: -2.87; 95% CI: -6.0 to 0.3) or blood pressure (WMD: -1.75; 95% CI: -5.6 to 2.1) between the treatment groups. Tremor was equally common in both groups (OR: 0.81; 95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI: -0.2 to 0.2). REVIEWER'S CONCLUSIONS Current evidence supports the use of CBA in patients with severe acute asthma who present to the emergency department to increase their pulmonary functions and reduce hospitalisation. Moreover, CBA treatment appears to be safe and well tolerated in patients who receive it.