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Does Aminophylline Benefit Adults Admitted to the Hospital for an Acute Exacerbation of Asthma?

David Huang, MD; Ralph G. O'Brien, PhD; Eloise Harman, MD; Larry Aull, PharmD; Stan Reents, PharmD; Jean Visser, PharmD; Gwowen Shieh, PhD; and Leslie Hendeles, PharmD
[+] Article, Author, and Disclosure Information

From the University of Florida, Gainesville, Florida. Requests for Reprints: Leslie Hendeles, PharmD, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486. Acknowledgments: The authors thank the internal medicine housestaff at the University of Florida and the respiratory therapy department staff and the fifth floor nursing staff of Shands Hospital for their assistance; Drs. Bill Brandes and Ted Carter for their assistance with the study protocol; and Joy Mitchell for processing and editing the typescript. Grant Support: In part by the University of Florida Foundation Pulmonary Research and Education Fund and the American Lung Association (Dr. Huang). AccuLevel kits for measurement of theophylline concentrations were provided by Syntex Medical Diagnostics.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(12):1155-1160. doi:10.7326/0003-4819-119-12-199312150-00001
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Objective: To determine the effect of adding intravenous theophylline (administered as aminophylline) to nebulizations of albuterol and intravenous methylprednisolone in adults hospitalized for acute asthma.

Design: Randomized, placebo-controlled, double-blind study.

Setting: Inpatient service of a tertiary-care, university teaching hospital.

Patients: 21 adults (22 to 48 years old)10 in the aminophylline group and 11 in the placebo group.

Interventions: Nebulized albuterol, 2.5 or 5.0 mg every 0.5 to 4 hours; intravenous methylprednisolone, 60 mg every 6 hours; and either individualized doses of aminophylline or placebo for 48 hours.

Measurements: Forced expiratory volume in 1 second (FEV1), the number of as needed albuterol nebulizations and total dose, asthma symptom scores, and adverse effects.

Results: At admission from the emergency department, the mean SD baseline FEV1 was 49% 19% of the predicted value in the aminophylline group and 43% 13% of the predicted value in the placebo group. The improvement in FEV1 at 3 hours was greater in the aminophylline group (29% 23% compared with 10% 10% in the placebo group; mean difference, 19 percentage points; 95% CI, 3 to 35 percentage points; P = 0.023). At 48 hours, FEV1 was 75% 19% of the predicted value in the aminophylline group and 58% 15% of the predicted value in the placebo group (mean difference, 17 percentage points; CI, 0.2 to 34.8 percentage points; P = 0.048). Aminophylline-treated patients required fewer nebulizations of albuterol (10.3 3.8 compared with 16.4 5.3; mean difference, 6.1;CI, 10.3 to 1.8) and less total dosage (34 16 mg compared with 70 34 mg; mean difference, 36 mg; CI, 60.6 to 11.3 mg P = 0.02). No statistical differences were observed in asthma symptom scores or frequency of adverse effects.

Conclusions: Individualized doses of intravenous theophylline added to frequent nebulizations of albuterol and intravenous methylprednisolone appear to benefit adults admitted to the hospital with acute asthma and are well tolerated when serum concentrations are maintained in the therapeutic range.


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Figure 1.
Time course of improvement in FEV1 in each patient.1topbottom1

Broken lines represent the percentage improvement in FEV over baseline in each patient treated with aminophylline ( ) or placebo ( ) expressed as a percentage of achievable improvement assuming that the maximum possible FEV is 100% predicted for age, height, sex, and race. Solid lines indicate the means for each group.

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Figure 2.
Mean improvement in FEV1.Top.11PBottom.tP

Log-linear regression fit of mean and 95% CIs of percentage improvement in FEV for each group. The circles represent the mean values for each treatment (filled circles = aminophylline, open circles = placebo). By definition, all patients had 0% improvement at baseline. The linear fit for hours 3 to 48 (log-scaled) was excellent. Mean SD percentage improvement in FEV at hour 3 was 29% 23% in the patients treated with aminophylline and 10% 10% in the patients given placebo ( = 0.023, two-tailed). After 3 hours, mean rates of improvement in the two groups (slopes of the fitted lines) were not statistically different. Mean difference between treatments and associated 95% CIs at each measured time point. Intervals excluding 0% indicate that -tests are significant at > 0.05, two-tailed.

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Figure 3.
Requirements for as-needed nebulized albuterol.2P

Each data point represents the number of as-needed nebulizations and total dose of albuterol required during the 48-hour study period for each patient (closed circles = aminophylline, open circles = placebo). The triangles represent mean values for aminophylline () and placebo () recipients. Aminophylline-treated patients received less albuterol, averaging 10.3 nebulizations and a total dose of 34 mg, compared with 16.4 nebulizations and a total dose of 70 mg for patients given placebo (Hotelling T , = 0.022).

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