***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Our investigation supports the use of intravenous salbutamol as an alternative to aminophylline in the early stages of acute severe asthma .  Salbutamol proved to be a marginally better bronchodilator and is likely to cause less gastrointestinal side effects than aminophylline , but tachycardia and generalized tremor are more frequent with this drug The role of bronchodilator regimens combining a sympathomimetic and a methylxanthine in the treatment of acute exacerbations of asthma remains controversial . This report describes the outcome of 157 emergency room visits for asthma in which patients were r and omly assigned to single-drug therapy with intravenous aminophylline , subcutaneous epinephrine , or inhaled isoproterenol or to one of three regimens combining a sympathomimetic and a methylxanthine . The increase in one-second forced expiratory volume after one hour of treatment with the two-drug combinations ( 0.79 + /- 0.07 liter ) was significantly greater than for epinephrine alone ( 0.57 + /- 0.08 liter ; p less than 0.05 ) but did not differ significantly from that occurring with therapy with isoproterenol alone ( 0.72 + /- 0.09 liter ; p = NS ) . This disparity reflects the greater bronchodilation effected by isoproterenol as a single agent than by epinephrine , in the dosing schedules and routes of administration chosen . Among patients presenting with severe airflow obstruction ( one-second forced expiratory volume 35 percent or less of normal ) , the bronchodilator response to isoproterenol alone was 0.88 + /- 0.14 liter versus 0.51 + /- 0.11 for epinephrine alone ( p less than 0.05 ) . It is concluded that the observed benefit derived from use of combination therapy depends on the dosage and potency of the particular sympathomimetic to which a methylxanthine is added , and on the severity of the airflow obstruction at presentation In patients with acute exacerbations of asthma , the intravenous administration of bronchodilators , such as salbutamol , entails the potential risk of worsening pulmonary gas exchange , despite an amelioration of airflow obstruction . The present study was design ed to investigate the effect of intravenous aminophylline on pulmonary gas exchange in patients hospitalized with a severe exacerbation of asthma . We studied 12 patients ( aged 41 + /- 13 yrs ) admitted to the hospital because of an exacerbation of asthma . The study was of a r and omized , double-blind , placebo-controlled design . Six patients were treated with intravenous aminophylline and six received placebo , in addition to st and ard treatment with inhaled salbutamol and intravenous corticosteroids .  Forced spirometry , respiratory gas exchange , ventilation-perfusion relationships assessed with the multiple inert gas elimination technique , and systemic haemodynamics were measured at baseline and 60 min after treatment started . In the aminophylline-treated group , mean theophylline plasma levels increased to 15.2 + /- 3.6 micrograms.ml-1 , forced expiratory volume ( FEV1 ) increased by 17 + /- 12 % , and forced vital capacity ( FVC ) by 16 + /- 10 % . The mean changes in FEV1 and FVC in the aminophylline-treated group were significantly higher than in the placebo-treated group . Likewise , minute ventilation increased by 23 + /- 14 % and arterial carbon dioxide tension ( PaCO2 ) decreased by 0.4 + /- 0.3 kPa ( 3 + /- 2 mmHg ) during aminophylline infusion . No significant changes in arterial oxygen tension ( PaO2 ) or in ventilation-perfusion distributions were shown in aminophylline-treated patients . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The role of aminophylline ( ethylene diamine salt of theophylline ) in the treatment of acute exacerbation of asthma has not been well established in children . OBJECTIVE The aim of the study was to determine the additional therapeutic benefit of intravenous aminophylline in the treatment of children hospitalized for acute asthmatic exacerbation and treated with inhaled bronchodilators and glucocorticoid therapy . METHODS Thirty-eight children aged from 2 to 16 years ( mean age 5.64 + /- 3.31 ) , admitted for acute exacerbation of asthma , participated in a prospect i ve , r and omized , double-blind , placebo-controlled study . All the subjects received methylprednisolone , administered intravenously , and nebulized salbutamol . The treatment group received intravenous aminophylline therapy and the placebo group received 0.9 % saline solution for 24 hours . RESULTS The number of salbutamol nebulizations needed and the clinical asthma scoring were recorded both at onset and at the end of 24 hours . There was no significant difference in either the mean number of nebulizations or the clinical asthma scores between the two groups ( P = .7843 , P = .8452 ) . CONCLUSION Intravenous aminophylline ( ethylene diamine salt of theophylline ) demonstrated no additional beneficial effect to the combination of beta adrenergic agonists and glucocorticoid treatment in acute asthma attack in children Twenty-one patients admitted to hospital with acute severe asthma were allocated in a r and om , single-blind manner to receive intravenous infusions for 24 hours or either aminophylline or salbutamol or a combination of the two drugs . Infusions were administered by a slow infusion pump with an initial loading dose given over 15 minutes , followed by a continuous lower dose of the drug 24 hours as follows : 1 . Aminophylline 0.285 mg/kg/min for 15 min followed by 0.014 mg/kg/min ( 20 mg/min . followed by 1 mg/min for a 70 kg subject ) . 2 . Salbutamol 0.285 microgram/kg/min for 15 min followed by 0.057 microgram/kg/min ( 20 microgram/min followed by 4 microgram/min for a 70 kg subject ) . 3 . Combined regimen of the above infusions . In addition each patient received intravenous hydrocortisone ( 4 g ) and potassium chloride ( 4 g ) in 2 litres of 5 % dextrose infused over 24 hours amd 35 % oxygen given via a Ventimask . Peak expiratory flow rates showed a significant improvement after 15 minutes treatment with aminophylline and the combined infusion , but this was not seen until 60 minutes with the salbutamol infusion . No synergistic bronchodilator effect was seen with the combined infusion . The results show that intravenous aminophylline is superior to intravenous salbutamol in the doses given in the initial treatment of acute asthma and that the combination when given intravenously is not better than aminophylline alone BACKGROUND The purpose of this study was to test the contribution of aminophylline in improving peak expiratory flow rate ( PEFR ) during emergency department treatment of acute asthma when metaproterenol sulfate and steroid therapy are also provided . METHODS In a prospect i ve , r and omized , double-blind , and placebo-controlled trial at a municipal hospital emergency department , 44 patients with acute asthma , aged 18 to 45 years , with theophylline levels below 28 mumol/L , who had failed to achieve a PEFR of 40 % predicted after one nebulized metaproterenol treatment , were recruited . An aminophylline or placebo loading dose and maintenance infusion were administered . All patients received hourly nebulized metaproterenol and initial methylprednisolone sodium succinate . The PEFR was measured hourly for 5 hours . Two-factor repeated- measures analysis of variance of improvement in PEFR ( [ final-initial PEFR]/predicted PEFR ) was assessed . RESULTS There was no difference in improvement of PEFR at any hour between the treatment and placebo groups . After 5 hours , the difference in improvement ratio was 0.40 ( aminophylline ) vs 0.36 ( placebo ) ( P = .30 ; n = 22 in each group ) . The treatment group suffered more tremor , nausea or vomiting , and palpitations ( P < .05 ) . CONCLUSION In the emergency department setting , aminophylline contributes no significant improvement in PEFR when beta 2-agonists and corticosteroids are being provided , while causing more side effects Acute , severe exacerbations of asthma present a challenge due to the significant morbidity associated with this presentation . For exacerbations that are refractory to initial treatments with inhaled and oral therapies , there is still doubt about which intravenous therapies are most likely to be helpful . β-2 agonists and aminophylline have differing mechanisms of action that also affect their adverse effects profiles and these are considered . A review of the available r and omised control trials suggests that a bolus of intravenous salbutamol may reduce symptoms and hasten recovery .  Aminophylline infusions may improve lung function , and in some studies have been shown to improve symptoms , but the evidence is not clear cut . Decisions about which treatment to use should include risk management considerations such as ease of prescription , preparation and administration factors and availability of high-dependency beds Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : There is a lack of consensus regarding second-line therapy in children with acute asthma who fail to the st and ard therapy .  Ketamine had bronchodilator property and may be useful in the treatment of acute asthma . Objective : The objective of this study was to evaluate the efficacy and safety of ketamine as compared to aminophylline in children with acute asthma who respond poorly to the st and ard therapy . Methods : This r and omized controlled trial included patients with acute asthma having Pediatric Respiratory Assessment Measure ( PRAM ) score ≥5 at 2 h of st and ard therapy . The enrolled patients received either intravenous ( IV ) ketamine or IV aminophylline . Primary outcome measure was change in PRAM score at the end of intervention . Secondary outcome measures included adverse effects , change in PO2 and PCO2 , need for mechanical ventilation , and duration of hospital stay . Results : The trial included 24 patients each in ketamine and aminophylline groups . The baseline parameters were similar between the groups . The primary outcome was similar in both the groups with a change in PRAM score of 4.00 ± 1.25 and 4.17 ± 1.68 ( P = 0.699 ) in ketamine and aminophylline groups , respectively . The secondary outcomes were not different between the groups . Conclusion : Ketamine and aminophylline were equally effective for children with acute asthma who responded poorly to the st and ard therapy Severe asthma is the most common respiratory emergency treated in casualty departments of most hospitals . Intravenous aminophylline has been the mainstay of bronchodilator treatment for several years , although sudden death may occur after rapid administration,1 2 and it may be cardiotoxic.3 We thought that a selective adrenoceptor agonist might therefore be worthy of trial , and we report here our results with single and double-blind comparative trials of intravenous aminophylline and salbutamol on 50 patients with severe asthma Thirty-seven patients with severe asthma were r and omized into three groups and treated double-blindly with either aminophylline , epinephrine , or a combination of these two for one hour and then with both drugs for an additional hour . All patients began with plasma theophylline levels less than 10 µg/ml and all achieved 17 µg/ml . Epinephrine produced 134 % improvement in FEV1 in one hour compared to 38 % improvement produced by aminophylline . Epinephrine and combination therapy produced the same amount of bronchodilatation in one hour . Patients whose initial PEFR was ≦100 l/min failed to improve with aminophylline alone . After two hours of treatment , there was no difference in FEV1 or PEFR among the three groups . Arrhythmias and vomiting occurred more frequently when aminophylline was used and these adverse responses did not correlate with plasma theophylline levels STUDY OBJECTIVE To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma . DESIGN R and omized , double-blind , placebo-controlled trial throughout the study . SETTING University Hospital Clinical Research Center . PATIENTS Forty-four patients admitted from the emergency room with a primary diagnosis asthma ; 39 patients completed the study . INTERVENTIONS Patients received either intravenous aminophylline or placebo in addition to frequent nebulized albuterol ; prednisone 0.5 mg/kg body weight every 6 h orally ; and supplemental oxygen . Aminophylline infusion rates were adjusted to achieve serum theophylline concentrations of 10 to 20 micrograms/ml . Changes were made in placebo inf 
    Output:
    
Theophylline was not significantly different from other drugs in its effects on respiratory rate , forced vital capacity ( FVC ) , peak expiratory flow rate , admission rate , use of rescue medication , oxygen saturation , or symptom score .
Conclusion Given the low cost of theophylline , and its similar efficacy and rate of side effects compared with other drugs , we suggest that theophylline , when given with bronchodilators with or without steroids , is a cost-effective and safe choice for acute asthma exacerbations