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Scheduled and as-needed albuterol were equivalent for mild asthma

ACP J Club. 1997 Jan-Feb;126:18. doi:10.7326/ACPJC-1997-126-1-018

Source Citation

Drazen JM, Israel E, Boushey HA, et al., for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. N Engl J Med. 1996 Sep 19;335:841-7.



To compare regularly scheduled albuterol treatment with as-needed treatment in patients with mild asthma.


26-week randomized, double-blind, placebo-controlled trial.


U.S. multicenter study.


255 patients (mean age 29 y, 56% women, 33% minorities) who had mild asthma. Inclusion criteria were forced expiratory volume in 1 second (FEV1) ≥ 70% of predicted value, age 12 to 55 years, concentration of methacholine required to decrease the FEV1 by 20% (PC20) ≤ 16 mg/mL, current β-agonist use of 6 to 56 puffs/wk, no corticosteroid use in the past 6 weeks, and no smoking for the past year.


During a 6-week run-in period, all patients regularly used a placebo inhaler (2 puffs 4 times/d) and took as-needed puffs of open-label albuterol. During a 16-week double-blind treatment period, patients were allocated to regularly scheduled albuterol plus as-needed albuterol (n = 126) or to regularly scheduled inhaled placebo plus as-needed albuterol (n = 129). All patients received inhaled placebo plus open-label as-needed albuterol for a 4-week withdrawal period. 230 patients (90%) completed the trial.

Main outcome measures

Peak expiratory flow rate (PEFR), peak flow variability, asthma symptoms, quality of life, change in FEV1 response to bronchodilator, PC20, asthma exacerbations, and treatment failure.

Main results

Regularly scheduled albuterol use differed from as-needed use for 2 outcomes: From the end of the treatment period to the end of the withdrawal period, mean evening PEFR decreased 7.7 L/min in the regularly scheduled albuterol group and increased 1.3 L/min in the as-needed group (P = 0.021 for the difference between groups). From the end of the run-in period to the end of the treatment period, FEV1 response to albuterol increased 1.8% in the regularly scheduled albuterol group and decreased 1.5% in the as-needed group (P = 0.005 for the difference between groups). No difference was seen for changes in morning PEFR, peak flow variability, PC20, FEV1, supplemental albuterol use, exacerbations, symptoms, or treatment failure.


In mild asthma, the regularly scheduled use of albuterol, compared with as-needed use, had no deleterious effect on asthma control but also did not confer any additional benefit.

Source of funding: National Institutes of Health.

For article reprint: Dr. J.M. Drazen, Respiratory Disease Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. FAX 617-732-7421.


An unanswered question in asthma management is what to do with patients who have mild asthma and are not adequately treated with as-needed, short-acting, inhaled β-agonists. Current guidelines recommend that regularly scheduled inhaled β-agonists be considered part of a more intensive therapy regimen in patients whose condition is not controlled with as-needed β-agonists; however, studies in patients with more severe asthma have raised the issue of an association between increased airway hyperresponsiveness and the regular use of these inhaled agents (1, 2).

Drazen and colleagues address the question of whether regularly scheduled inhaled β-agonists provide additional clinical benefit or result in any deleterious effects in patients with mild asthma who previously found adequate relief by inhaling these agents on an as-needed basis. Some limitations of this study deserve mention. First, the patients had extremely mild asthma and a mean daily β-agonist use of only 1.5 puffs/d, had a morning PEFR of approximately 420 L/min, and were studied for a relatively short period. These patients would most likely use an inhaled β-agonist as their sole asthma treatment; therefore, the results should not be extrapolated to patients with more severe asthma. Second, although the study duration was adequate based on previous work by Sears and colleagues (2), the outcome is uncertain for patients with mild asthma who receive regularly scheduled β-agonists for a longer period. The study by Drazen and colleagues does provide some reassurance that regular use of these agents does not result in substantial increases in bronchial hyperreactivity or loss of asthma control in patients with mild asthma who received this treatment for 16 weeks; however, the study was not designed to identify subsets of patients with mild asthma in whom constant β-stimulation would be harmful. This remains an open and unexplored facet of the ongoing β-agonist controversy. Nevertheless, the finding that regularly scheduled inhaled β-agonists had no additional efficacy, combined with the remaining safety concerns, supports the recommendation that they be used only on an as-needed basis in the management of asthma.

Peter K. Honig, MD
U.S. Food and Drug AdministrationRockville, Maryland, USA


1. National Heart, Lung, and Blood Institute. Guidelines for the Diagnosis and Management of Asthma. U.S. Department of Health and Human Services, publication no. 91-3042. Bethesda: National Institutes of Health; 1991.

2. Sears MR, Taylor DR, Print CG, et al. Lancet. 1990;336:1391-6.