Randomised placebo controlled trial of beta agonist dose reduction in asthma

Abstract
Many patients continue to take regular beta agonists, often at high doses, contrary to national and international guidelines. Some studies have suggested that this can worsen asthma control, but whether such patients can reduce their dose of beta agonist and whether they would benefit from this has not been determined. Reduction of beta agonist dose was studied in a placebo controlled parallel group study. Following a run in period, 33 subjects with asthma taking regular beta agonists were converted to an equivalent dose of terbutaline via a Turbohaler. Two weeks later terbutaline was continued at the same dose or changed to placebo in two stages a week apart. The change over period was covered by an increased dose of inhaled steroid to attenuate any immediate effects of the change in dose. Subjects then attended weekly for six weeks for measurement of forced expiratory volume in one second (FEV1) and the dose of methacholine that produced a 20% fall in FEV1 (PD20). Peak expiratory flow (PEF) and symptom scores were recorded twice daily throughout the study. Exacerbations, lung function, bronchial responsiveness, bronchodilator response, beta agonist use, and symptoms were compared before and six weeks after reduction in the dose of beta agonist. Twenty five of the 33 subjects completed the study; three patients in each group withdrew due to an asthma exacerbation. The median terbutaline dose fell from 2500 to 500 micrograms/day in the beta agonist reduction group and from 3000 to 2250 micrograms/day in the control group. There were small non-significant changes in FEV1, PEF, symptom scores and PD20 methacholine over the course of the study. The FEV1 response to a beta agonist was greater in those who reduced their beta agonist dose than in the control group although the final FEV1 achieved was the same. Patients with asthma taking high doses of beta agonists can reduce the amount of beta agonist they use without a significant change in their asthma control. There was no evidence of improved asthma control with beta agonist dose reduction.