Long-term budesonide improves symptoms, lung function, and airway responsiveness compared with terbutaline in newly detected asthma
ACP J Club. 1991 Nov-Dec;115:82. doi:10.7326/ACPJC-1991-115-3-082
Haahtela T, Järvinen M, Kava T, et al. Comparison of a β2-agonist, terbutaline, with an inhaled corticostertoid, budesonide, in newly detected asthma. N Engl J Med. 1991 Aug 8;325:388-92. [PubMed ID: 2062329]
To compare the long-term effect of the anti-inflammatory inhaled steroid, budesonide, with the bronchodilating inhaled β2-agonist, terbutaline, in patients with newly diagnosed asthma.
Randomized, double-blind, controlled trial. A 6-week pretreatment period preceded the 96-week trial.
5 centers in Scandinavia.
Patients were nonsmoking adults with symptoms of asthma for < 12 months, showing > 15% increase in forced expiratory volume in 1 s (FEV1) in response to inhalation of a β2-agonist, or a > 15% decrease in FEV1 after an exercise-tolerance test. The FEV1 had to drop > 15% after a histamine challenge. Patients receiving regular treatment with corticosteroids or cromolyn were excluded. 103 patients were randomized and included in intention-to-treat analysis; 6 proved to be ineligible.
All patients inhaled terbutaline, 375 µg twice a day during the pretreatment period; 50 patients were then randomized to inhaled budesonide, 600 µg twice a day and 53 continued terbutaline. A spacer was used for all inhaled medication. Supplemental terbutaline, oral theophylline, and oral prednisolone for exacerbations were permitted. Using diaries, patients recorded their peak expiratory flow (PEF) before morning and evening medication, and supplemental therapy, adverse events, and symptoms (dyspnea, cough, and sputum production).
Main outcome measures
Changes in FVC, FEV1,histamine challenge, PEF, asthma score, and supplemental medications were assessed during the first 12 weeks, 44 to 48 weeks, and 92 to 96 weeks after randomization.
No difference existed between treatment groups in FVC. FEV1 increased by a mean of 0.13 liter in the budesonide group compared with the pretreatment period (P < 0.05), but did not change for the terbutaline group. There was a negative trend in FEV1 in the terbuline group (P < 0.05) but not in the budesonide group. However, the 2 groups did not differ significantly (P > 0.05). Patients receiving budesonide had a greater decrease in bronchial responsiveness within 6 weeks (P < 0.001). The budesonide group showed greater increases in PEF values (32.8 L/min vs 4.8 L/min for terbutaline, P < 0.001), greater reductions in asthma symptoms (P < 0.01), and less use of supplemental β2-agonist medication (P< 0.01). 10 patients (19%) withdrew for insufficient treatment effect from the terbutaline group compared with 1 (2%) from the budesonide group.
A sustained improvement in symptoms, lung function, and airway responsiveness occurred in patients with newly detected mild asthma who received budesonide for 2 years compared with patients who received terbutaline.
Source of funding: Not stated.
Address for article reprint: Dr T. Haahtela, Department of Allergic Diseases, Helsinki University Central Hospital, Meilahdentie 2, SF-00250 Helsinki, Finland.
This is a well-designed clinical trial that confirms the findings of previous smaller studies (1, 2). Several aspects of the design and reporting add to the clinical applicability of the study, including the 2-year duration of the trial and details regarding failure of therapy.
The concepts regarding treatment of asthma are currently undergoing major revision (3). In the past, therapy for asthma has been focused on relieving the bronchospastic component of the disease. Airway hyper-responsiveness is now considered a consequence of inflammation; thus, the prevention of the asthmatic attack with an antiinflammatory drug is preferred. This study confirms that airway hyper-responsiveness is diminished over a long period when inhaled corticosteroids are administered on a regular basis.
The data from this trial support the authors' contention that inhaled corticosteroid is an effective first-line treatment in patients with newly detected mild asthma. The practitioner should consider prescribing an inhaled corticosteroid in addition to an inhaled bronchodilator as an early therapeutic intervention in patients with asthma severe enough to interfere with sleep or daytime activities, particularly for patients requiring the use of an inhaled bronchodilator more than 2 or 3 times a day. Strategies to maximize compliance and patient education in aerosol-inhalation technique are critical for successful therapy.
Praveen N. Mathur, MD
Indiana UniversityIndianapolis, Indiana, USA.
2. Juniper EF, Kline PA, Vanzieleghem MA, et al. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis. 1990;142:832-6.
3. National Heart, Lung, and Blood Institute. National Asthma Education Program Expert Panel Report. Executive Summary: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Maryland: National Institutes of Health; 1991.