In this double blind, randomized controlled trial, we compared the bronchodilatory action of budesonide/formoterol and budesonide/salbutamol in mild acute exacerbation of asthma. We observed that budesonide/formoterol had rapid onset of bronchodilatory action similar to that of budesonide/salbutamol in mild acute exacerbation of asthma in children 5-15 years of age. Both clinical and spirometric parameters at different time points after the administration of the drugs from 1 to 60 min showed no statistically significant difference in both the groups. Children within both the groups showed significant improvement in FEV1 as well as MPIS. There was no significant difference in side effects.
Few studies in children which compared formoterol with salbutamol or terbutaline delivered by different routes like nebulisation or dry powder inhalation in acute exacerbation also concluded that both the drugs are equally efficacious in acute exacerbation [6–8].
There are no published studies that have compared budesonide/formoterol with budesonide/salbutamol delivered by metered dose inhaler with spacer in acute exacerbation of asthma in children. Studies in adults comparing rapid bronchodilator response of formoterol and salbutamol suggested comparable results [11–13].
A recent study by Bussamra et al. compared formoterol (12 μg) delivered by aerolizer and terbutaline (0.5 mg) delivered by dry powder inhaler (Turbohaler) in mild to moderate acute exacerbation in children and reported similar rapid bronchodilator action . In this study, all children received up to three doses of medications at interval of 20 min till they achieved predefined spirometric parameters. All participants received oral steroids. They concluded that both drugs had similar clinical and spirometric improvement, variations in FEV1 of 19.5% and 15.3% were observed in the formoterol and terbutaline groups, respectively. Rodriguez et al. compared formoterol and salbutamol in 50 children aged 5 to 12 years with acute asthma exacerbations of any severity. Children received either single dose of 25 μg formoterol fumarate by nebuliser or 3 doses of Salbutamol (Albuterol) every twenty minutes for one hour by nebuliser. Symptoms score, oxygen saturation and lung function testing recorded before and one hour after commencing treatment showed significant improvement . The results of our study are in concordance with these studies even though we enrolled children with mild exacerbations and used single dose of either medication delivered by MDI and spacer.
The results of our study and other studies suggest that formoterol has rapid bronchodilator action similar to salbutamol or terbutaline and possibly can be used as rescue drug for acute exacerbations in children. We had earlier compared bronchodilator action of two long acting beta agonists (formoterol and salmeterol) at 60 min in a randomized controlled trial and observed similar improvement in FEV1 . In this study, no comparisons were done in first 10 min of administration of the drugs. International guidelines recommend against monotherapy with LABA in the management of asthma .
However, there are few concerns regarding long-term, frequent use of LABAs. The extent of tolerance to β-adrenoceptor agonists is dependent on the dose and duration of treatment. A randomized, double-blind, placebo-controlled, crossover trial in adults by Haney and Hancox  assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. They concluded that the bronchodilator response to salbutamol was significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment may occur in patients treated with long-acting beta-agonists. Therefore, it is important to document that repeated doses of formoterol as rescue drugs will not affect response to treatment in acute exacerbation of asthma.
A systematic review evaluated the effects of the combination of LABA and inhaled corticosteroids versus a higher dose of inhaled corticosteroids on the risk of asthma exacerbations . The authors concluded that combination of LABA and ICS was more effective in reducing the risk of exacerbations requiring oral corticosteroids than a higher dose of ICS in adolescents and adults; in children there was no significant reduction, but rather a trend towards an increased risk of oral steroid-treated exacerbations and hospital admissions was observed . Hence, the issue of safety in children on long term use is yet to be resolved.
The strength of our study was that it was a double blind, randomized controlled trial with adequate sample size. We enrolled children with mild acute exacerbation of asthma. We used metered dose inhalers to deliver single dose (two actuations of MDI for each drug) as these devices are commonly used in the management of asthma. Unlike previous studies, we used a combination of ICS and formoterol. Clinical and spirometric parameters were monitored as early as 1-min post administration of the drug and frequent observations at 5, 15, 30 and 60 min were done.
There are few limitations of our study. As the study was done in children with only mild acute exacerbation, the results cannot be extrapolated to children with moderate to severe exacerbation. The evaluation were done only for an hour after administration; the advantages of formoterol + ICS versus salbutamol + ICS are more likely to be seen with longer follow-up periods, such as upto 3-12 h post-dosing.