The timing of salbutamol treatment for asthma may impact comparative bronchodilator responses compared with budesonide/formoterol, according to recent research published in the European Respiratory Journal.

While the primary outcome of the study showed no difference in the magnitude of bronchodilation for either group, the secondary analysis showed the time of measurement impacted the comparative bronchodilator responses for repeated budesonide/formoterol and salbutamol administration.

The study’s findings highlight the comparative efficacy of repeated administration of budesonide/formoterol with salbutamol in the acute exacerbation setting. The research also gives insight into the greater efficacy of budesonide/formoterol reliever therapy for reducing severe exacerbation risk with long-term use.

The researchers performed an open-label crossover trial of 39 adults with asthma who received one of two treatment regimens. The first consisted of salbutamol (200 µg) through a metered-dose inhaler timed at baseline, 30 minutes, 60 minutes, and 90 minutes followed by nebulized salbutamol (2.5 mg) timed at 120 minutes, 140 minutes, 160 minutes, and 420 minutes. 

The second group received one actuation of budesonide/formoterol (200/6 µg) through an inhaler at baseline, 30 minutes, 60 minutes, and 90 minutes followed by two actuations at 120 minutes, 140 minutes, 160 minutes, and 420 minutes.

Researchers assessed forced expiratory volume in 1 second (FEV₁) at 180 minutes as a primary outcome, with secondary outcomes of FEV₁, exhaled nitric oxide fraction (FeNO) and modified Borg dyspnea scale score at other time frames as well as serum potassium, blood eosinophil levels, heart rate, and corrected QT interval using Fridericia’s formula.

The results showed a mean change in FEV₁ at 180 minutes compared with baseline of 0.71 L for the salbutamol group and 0.58 L for the budesonide/formoterol group with a non-significant mean paired difference of −0.10 L (P = .088). 

A secondary analysis showed the salbutamol group had significantly improved FEV₁ between 30 minutes and 240 minutes, but not between 360 minutes and 420 minutes. The salbutamol group also had significantly lower serum potassium, more adverse events, and a higher heart rate than the budesonide/formoterol group, the researchers said.

The use of budesonide/formoterol, based on the study’s findings, does not result in superior bronchodilation compared to salbutamol. Use of this combination may actually result in lesser bronchodilation over the first 4 hours—the timespan when clinical decisions regarding admission to hospital are made.

The study does suggest that budesonide/formoterol’s efficacy is achieved despite a lesser acute, although more prolonged, bronchodilator response. This suggests that the inhaled corticosteroid component of reliever therapy, continuously adjusted according to changes in symptoms, is the key factor to this efficacy.

“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,” Nethmi Kearns, MBChB, of the Medical Research Institute of New Zealand said. “The nature of as-required relief is that patients use as much as necessary and the real-life use of these inhalers leads to different patterns of use. However, it is pertinent to remember that asthma mortality epidemics have been associated with high-dose preparations of β2-agonist and that the relatively lower β2-agonist dose may have a potential safety advantage, as suggested by our findings.”

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Disclosures: Beasley declared financial ties to drugmakers. See full study for details. This study was funded by AstraZeneca.