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March 18, 1988, Vol 259, No. 11 >
ARTICLE | March 18, 1988

Aminophylline Treatment in Severe, Acute Asthma: Title and subTitle BreakA Meta-analysis FREE

Benjamin Littenberg, MD
[+] Author Affiliations

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JAMA. 1988;259(11):1678-1684. doi:10.1001/jama.1988.03720110040032
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References

Aminophylline is routinely recommended as a basic part of the emergency treatment of asthma. A comprehensive search found 13 reports of controlled trials of intravenous aminophylline therapy in severe, acute asthma. These studies compared aminophylline therapy with treatment with either albuterol (salbutamol), epinephrine, or other bronchodilators. The 13 reports did not agree. Seven reported no difference in spirometric values between aminophylline treatment and the control regimens. Three found aminophylline treatment superior. Three favored the control regimen. The results of the 13 trials were reanalyzed and pooled. Overall, there was no difference between the aminophylline-treated groups and the control groups. Sensitivity analysis suggests that aminophylline therapy is ineffective alone but may be more effective than single-drug therapy when combined with an injected β-agonist. Despite widespread practice, available trials do not provide adequate evidence to support or reject the use of aminophylline in the treatment of severe, acute asthma.

(JAMA 1988;259:1678-1684)

REFERENCES

1 +
Persson CGA:  On the medical history of xanthines and other remedies for asthma. Thorax 1985;;40:881-886.
2 +
Hermann G, Aynesworth MB:  Successful treatment of persistent extreme dyspnea, 'status asthmaticus': Use of theophylline ethylene diamine (aminophylline USP) intravenously. J Lab Clin Med 1937;;23:135-148.
3 +
Bresnick E, Woodard WK, Sageman CB:  Fatal reactions to intravenous administration of aminophylline. JAMA 1948;;136:397-398.
4 +
Mitenko PA, Ogilvie RI:  Rational intravenous doses of theophylline. N Engl J Med 1973;;289:600-603.
5 +
Glass GV, McGaw B, Smith ML: Meta-analysis in Social Research . Beverly Hills, Calif, Sage Publications Inc, 1981;.
6 +
Light RJ, Pillemer DB: Summing Up: The Science of Reviewing Research . Cambridge, Mass, Harvard University Press, 1984;.
7 +
L'Abbe KA, Detsky AS, O'Rourke K:  Meta-analysis in clinical research. Ann Intern Med 1987;;107:224-233.
8 +
Chalmers TC, Smith H, Blackburn B, et al:  A method for assessing the quality of a randomized control trial. Controlled Clin Trials 1981;;2:31-49.
9 +
Moses LE: Think and Explain With Statistics . Reading, Mass, Addison-Wesley Publishing Co, 1986;, p 54.
10 +
Hills M, Armitage P:  The two-period crossover clinical trial. Br J Clin Pharmacol 1979;;8:7-20.
11 +
Beswick K, Davies J, Davey AJ:  A comparison of intravenous aminophylline and salbutamol in the treatment of severe bronchospasm. Practitioner 1975;;214:561-566.
12 +
Femi-Pearse D, George WO, Ilechukwu ST, et al:  Comparison of intravenous aminophylline and salbutamol in severe asthma. Br Med J 1977;;1:491.
13 +
Rossing TH, Fanta CH, Goldstein DH, et al:  Emergency treatment of asthma: Comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir Dis 1980;;122:365-371.
14 +
Appel D, Shim C:  Comparative effect of epinephrine and aminophylline in the treatment of asthma. Lung 1981;;159:243-254.
15 +
Sharma TN, Gupta RB, Gupta PR, et al:  Comparison of intravenous aminophylline, salbutamol and terbutaline in acute asthma. Indian J Chest Dis Allied Sci 1984;;26:155-158.
16 +
Williams SJ, Parrish RW, Seaton A:  Comparison of intravenous aminophylline and salbutamol in severe asthma. Br Med J 1975;;4:685.
17 +
Tribe AE, Wong RM, Robinson JS:  A controlled trial of intravenous salbutamol and aminophylline in acute asthma. Med J Aust 1976;;2:749-752.
18 +
Evans WV, Monie RDH, Crimmins J, et al:  Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Br J Dis Chest 1980;;74:385-389.
19 +
Pierson WE, Bierman CW, Stamm SJ, et al:  Double-blind trial of aminophylline in status asthmaticus. Pediatrics 1971;;48:642-646.
20 +
Josephson GW, MacKenzie EJ, Lietman PS, et al:  Emergency treatment of asthma: A comparison of two treatment regimens. JAMA 1979;;242:639-643.
21 +
Rossing TH, Fanta CH, McFadden ER:  A controlled trial of the use of single versus combined-drug therapy in the treatment of acute episodes of asthma. Am Rev Respir Dis 1981;;123:190-194.
22 +
Fanta CH, Rossing TH, McFadden ER:  Emergency treatment of asthma: Relationships among therapeutic combinations, severity of obstruction and time course of response. Am J Med 1982;; 72:416-422.
23 +
Siegel D, Sheppard D, Gelb A, et al:  Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. Am Rev Respir Dis 1985;;132:283-286.
24 +
Tukey JW:  Some thoughts on clinical trials, especially problems of multiplicity. Science 1977;; 198:679-684.
25 +
Browner WS, Newman TB:  Are all significant P values created equal? The analogy between diagnostic tests and clinical research. JAMA 1987;; 257:2459-2463.
26 +
Hendeles L, Bighley L, Richardson RH, et al:  Frequent toxicity from IV aminophylline infusions in critically ill patients. Drug Intell Clin Pharm 1977;;11:12-18.
27 +
Jacobs MH, Senior RM, Kessler G:  Clinical experience with theophylline. JAMA 1976;;235: 1983-1986.
28 +
Messer J, Reitman D, Sacks H, et al:  Association of adrenocorticosteroid therapy and pepticulcer disease. N Engl J Med 1983;;309:21-24.
29 +
Littenberg B, Gluck EH:  A controlled trial of methylprednisolone in the emergency treatment of acute asthma. N Engl J Med 1986;;314:150-152.
30 +
Storr J, Barrell E, Barry W, et al:  Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet 1987;;1:880-882.
31 +
Ellul-Micallef R:  The acute effects of corticosteroids in bronchial asthma. Eur J Respir Dis 1982;;63( (suppl 122) ):118-125.

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1 +
Persson CGA:  On the medical history of xanthines and other remedies for asthma. Thorax 1985;;40:881-886.
2 +
Hermann G, Aynesworth MB:  Successful treatment of persistent extreme dyspnea, 'status asthmaticus': Use of theophylline ethylene diamine (aminophylline USP) intravenously. J Lab Clin Med 1937;;23:135-148.
3 +
Bresnick E, Woodard WK, Sageman CB:  Fatal reactions to intravenous administration of aminophylline. JAMA 1948;;136:397-398.
4 +
Mitenko PA, Ogilvie RI:  Rational intravenous doses of theophylline. N Engl J Med 1973;;289:600-603.
5 +
Glass GV, McGaw B, Smith ML: Meta-analysis in Social Research . Beverly Hills, Calif, Sage Publications Inc, 1981;.
6 +
Light RJ, Pillemer DB: Summing Up: The Science of Reviewing Research . Cambridge, Mass, Harvard University Press, 1984;.
7 +
L'Abbe KA, Detsky AS, O'Rourke K:  Meta-analysis in clinical research. Ann Intern Med 1987;;107:224-233.
8 +
Chalmers TC, Smith H, Blackburn B, et al:  A method for assessing the quality of a randomized control trial. Controlled Clin Trials 1981;;2:31-49.
9 +
Moses LE: Think and Explain With Statistics . Reading, Mass, Addison-Wesley Publishing Co, 1986;, p 54.
10 +
Hills M, Armitage P:  The two-period crossover clinical trial. Br J Clin Pharmacol 1979;;8:7-20.
11 +
Beswick K, Davies J, Davey AJ:  A comparison of intravenous aminophylline and salbutamol in the treatment of severe bronchospasm. Practitioner 1975;;214:561-566.
12 +
Femi-Pearse D, George WO, Ilechukwu ST, et al:  Comparison of intravenous aminophylline and salbutamol in severe asthma. Br Med J 1977;;1:491.
13 +
Rossing TH, Fanta CH, Goldstein DH, et al:  Emergency treatment of asthma: Comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir Dis 1980;;122:365-371.
14 +
Appel D, Shim C:  Comparative effect of epinephrine and aminophylline in the treatment of asthma. Lung 1981;;159:243-254.
15 +
Sharma TN, Gupta RB, Gupta PR, et al:  Comparison of intravenous aminophylline, salbutamol and terbutaline in acute asthma. Indian J Chest Dis Allied Sci 1984;;26:155-158.
16 +
Williams SJ, Parrish RW, Seaton A:  Comparison of intravenous aminophylline and salbutamol in severe asthma. Br Med J 1975;;4:685.
17 +
Tribe AE, Wong RM, Robinson JS:  A controlled trial of intravenous salbutamol and aminophylline in acute asthma. Med J Aust 1976;;2:749-752.
18 +
Evans WV, Monie RDH, Crimmins J, et al:  Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Br J Dis Chest 1980;;74:385-389.
19 +
Pierson WE, Bierman CW, Stamm SJ, et al:  Double-blind trial of aminophylline in status asthmaticus. Pediatrics 1971;;48:642-646.
20 +
Josephson GW, MacKenzie EJ, Lietman PS, et al:  Emergency treatment of asthma: A comparison of two treatment regimens. JAMA 1979;;242:639-643.
21 +
Rossing TH, Fanta CH, McFadden ER:  A controlled trial of the use of single versus combined-drug therapy in the treatment of acute episodes of asthma. Am Rev Respir Dis 1981;;123:190-194.
22 +
Fanta CH, Rossing TH, McFadden ER:  Emergency treatment of asthma: Relationships among therapeutic combinations, severity of obstruction and time course of response. Am J Med 1982;; 72:416-422.
23 +
Siegel D, Sheppard D, Gelb A, et al:  Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. Am Rev Respir Dis 1985;;132:283-286.
24 +
Tukey JW:  Some thoughts on clinical trials, especially problems of multiplicity. Science 1977;; 198:679-684.
25 +
Browner WS, Newman TB:  Are all significant P values created equal? The analogy between diagnostic tests and clinical research. JAMA 1987;; 257:2459-2463.
26 +
Hendeles L, Bighley L, Richardson RH, et al:  Frequent toxicity from IV aminophylline infusions in critically ill patients. Drug Intell Clin Pharm 1977;;11:12-18.
27 +
Jacobs MH, Senior RM, Kessler G:  Clinical experience with theophylline. JAMA 1976;;235: 1983-1986.
28 +
Messer J, Reitman D, Sacks H, et al:  Association of adrenocorticosteroid therapy and pepticulcer disease. N Engl J Med 1983;;309:21-24.
29 +
Littenberg B, Gluck EH:  A controlled trial of methylprednisolone in the emergency treatment of acute asthma. N Engl J Med 1986;;314:150-152.
30 +
Storr J, Barrell E, Barry W, et al:  Effect of a single oral dose of prednisolone in acute childhood asthma. Lancet 1987;;1:880-882.
31 +
Ellul-Micallef R:  The acute effects of corticosteroids in bronchial asthma. Eur J Respir Dis 1982;;63( (suppl 122) ):118-125.

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