Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma

doi:10.1016/S0091-6749(98)70187-3

Journal of Allergy and Clinical Immunology

Volume 101, Issue 1, January 1998, Pages 14-23

https://doi.org/10.1016/S0091-6749(98)70187-3 Get rights and content

Abstract

Background: Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma. Objective: We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray. Methods: A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 μg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements. Results: Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed. Conclusion: Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children. (J Allergy Clin Immunol 1998;101:14-23.)

Section snippets

Study design

This was a randomized, double-blind, double-placebo study performed in 30 centers. The study subjects included both children and adults (6 to 65 years of age) with asthma who experienced dyspnea, cough, and wheezing and who required frequent bronchodilator treatment despite avoidance of allergens. These subjects were considered by their physicians to be candidates for continuous treatment. Within the month before randomization, patients were required to have an FEV ₁ greater than 50% of

RESULTS

Patient numbers, demographic characteristics, and previous experience with the study drugs are listed in Table II.

. Demographics of study patients

Empty Cell	Beclomethasone group(N = 384)	Theophylline group(N = 363)	Total(N = 747)
Age 6-17 yr
F	45	28	73
M	57	65	122
Age 18-65 yr
F	157	153	310
M	125	117	242
Race
Asian	3	2	5
Black	29	20	49
White	343	332	675
Hispanic	9	9	18
Exposure to study drugs within the month before screening
Neither beclometha-sone nor theophylline	194	190	384
Theophylline only	175	160	335
Beclomethasone only	15	13	28

*Entries are numbers

DISCUSSION

The aim of this investigation was to compare how well these two treatments control moderate asthma. The patient population had asthma severe enough that it was inadequately controlled by inhaled β-adrenergic agonists, but not so severe as to require more than occasional short courses of systemic glucocorticoids.

Both treatments were effective in achieving control and were accompanied by the anticipated effects. Both drugs acted promptly, although maximum reduction in symptoms was observed only

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^☆: *Members of the study group are listed in the appendix.

^☆☆: Supported by a grant from Allen and Hanburys, Research Triangle Park, N.C., to the American Academy of Allergy, Asthma and Immunology.

^★: Reprint requests: James T. Li, MD, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.

^★★: 1/1/85510

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Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma☆,☆☆,★,★★

Abstract

Section snippets

Study design

RESULTS

DISCUSSION

J Allergy Clin Immunol

J Pediatr

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

Lancet

The pathology of asthma with special reference to changes in the bronchial mucosa

J Clin Pathol

Pathology of mild, severe, and fatal asthma

Am J Respir Crit Care Med

Expert panel report on guidelines for diagnosis and management of asthma II

Inhaled corticosteroids reduce the severity of bronchial hyperresponsiveness in asthma but oral theophylline does not

Am Rev Respir Dis

Issues in the use of inhaled glucocorticoids

Am J Respir Crit Care Med

Candidiasis and dysphonia complicating beclomethasone treatment of asthma

J Allergy Clin Immunol

Standardization of spirometry, 1987 update

Am Rev Respir Dis

Reference spirometric values for spirometry using techniques and equipment that meets ATS and recommendations

Am Rev Respir Dis