Is Repeated-Dose Budesonide/Formoterol Superior to Salbutamol for Adult Asthma?

Woman using a bronchodilator, inhaler
Woman using a bronchodilator, inahler
Investigators compared budesonide/formoterol and salbutamol for their bronchodilator, systemic beta2-agonist, cardiovascular and adverse effects in adults with asthma.

Repeated administration of 200 µg salbutamol or budesonide/formoterol 200/6 µg results in different bronchodilator responses, depending on the time of measurement, according to a study published in the European Respiratory Journal.

The open-label, crossover, controlled trial, conducted at a single center, was designed to compare the bronchodilator effects as well as the systemic beta2-agonist, cardiovascular, and adverse effects of salbutamol 200 µg with those of repeated doses of budesonide/formoterol 200/6 µg in patients with stable asthma. Investigators enrolled adults with asthma aged 16 to 65 years, who had a forced expiratory volume in 1 second (FEV1) of 40% to 70% of predicted and bronchodilator reversibility with an FEV1 of 12% or above and over 200 ml. Study participants were randomly assigned to 2 treatment schedules: (1) salbutamol 200 µg administered through 2 actuations through a spacer at t = 0, 30, 60,  and 90 minutes, followed by salbutamol 2.5 mg administered via nebulizer at t =120, 140, 160, and 420 minutes; or (2) budesonide/formoterol 200/6 µg, given as 1 actuation by Turbuhaler at t = 0, 30, 60, and 90 minutes, followed by 2 actuations at t = 120, 140, 160 and 420 minutes. The primary outcome included FEV1 after 180 minutes. Secondary outcomes were repeated measures of FEV1, as well as serum potassium levels, heart rate, and adverse events.

Of the 39 randomly assigned patients, 2 withdrew because of adverse events (QTCF prolongation and T-wave abnormalities) after the first dose of salbutamol. The mean standard deviation (SD) changes from baseline FEV1 180 minutes after randomization for the salbutamol and budesonide/formoterol treatments were 0.71 (0.46) L and 0.58 (0.45) L, respectively. A mean (SD) paired difference of -0.10 (0.40) L and a model-based estimated difference of -0.12 L (95% CI, -0.25-0.02 L; P=.088) were observed. In the principal secondary analysis, salbutamol led to significantly higher FEV1 at 30 to 240 minutes but resulted in lower FEV1 at 360 and 420 minutes. Salbutamol also produced significantly lower serum potassium levels, higher heart rates, and more adverse events.

The study was limited by its open-label construction, which introduced potential bias. The researchers also studied adults with moderate to severe reversible airflow obstruction in an outpatient clinic setting rather than in an acute asthma setting, such as the emergency department (ED), resulting in findings that may not be generalizable to patients arriving at the ED with a severe exacerbation.

“Arguably, the clinical relevance of differences in bronchodilator efficacy in the community setting is a moot point, as the patient can simply take an additional dose if needed to relieve symptoms,” the study authors wrote. “However, it is pertinent to remember that asthma mortality epidemics have been associated with high-dose preparations of beta2-agonist and that the relatively lower beta2-agonist dose may have a potential safety advantage, as suggested by our findings.”

Disclosure: This research was supported by AstraZeneca Ltd. Please see the original reference for a full list of disclosures.


Kearns N, Bruce P, Williams M, et al. Repeated dose budesonide/formoterol compared to salbutamol in adult asthma: a randomised cross-over trial. Eur Respir J. Published online February 3, 2022. doi:10.1183/13993003.02309-2021