Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol
ED Bateman
1
L Fairall
1
DM Lombardi
0
R English
1
0
Hospital Municipal de Rehabilitacion Respiratoria 'Maria Ferrer'
,
Buenos Aires
,
Argentina
1
University of Cape Town Lung Institute
,
Cape Town
,
South Africa
Background: To compare the efficacy and safety of budesonide/formoterol (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting 2-agonist therapy. Methods: In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV1 40% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 g), were randomized to receive either budesonide/ formoterol (320/9 g, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 g]) or formoterol (9 g, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 g]). The primary efficacy variable was the average FEV1 from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured. Results: FEV1 increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated. Conclusion: Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a shortacting 2-agonist.
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Introduction
Patients presenting with symptoms of acute asthma are
traditionally treated with short-acting 2-agonists [1,2].
Formoterol is a long-acting 2-agonist with a rapid onset
of action, producing bronchodilation within 13 minutes
of inhalation [3-5]. This effect is comparable with that of
salbutamol [5], making formoterol suitable for the
treatment of acute asthma. In this setting, formoterol has
proved both safe and efficacious [6,7]. A large study
performed in an emergency room setting by Boonsawat and
colleagues [6] showed that high-dose formoterol was as
rapid and effective as high-dose salbutamol in reversing
bronchoconstriction in patients with severe asthma, but
formoterol produced greater improvements than
salbutamol in lung function over 4 hours. For this reason,
formoterol has been licensed for use as both maintenance
therapy and as an alternative to salbutamol and
terbutaline for the relief of acute asthma symptoms.
Asthma patients experiencing acute symptoms may use
their 2-agonist reliever medication repeatedly. This can
result in downregulation of 2-receptors and consequent
relative refractoriness to the bronchodilatory effects of this
class of drug [8,9]. High doses of inhaled corticosteroid
(ICS) have been reported to upregulate these receptors
and restore 2-agonist responsiveness [10].
In order to study the potential of this favourable
interaction, Pansegrouw [11] examined the use of combined ICS
and short-acting 2-agonist treatment in patients with
acute asthma who initially showed no response to
2-agonist therapy. It was reported that 'priming' patients with
ICS before commencing nebulised 2-agonist treatment
was more effective than therapy with the 2-agonist alone
at improving features of the exacerbation, including lung
function [11]. Although, to our knowledge, this study has
not been repeated, it raises the prospect that budesonide
and formoterol which are now available together in a
combination inhaler (Symbicort;
budesonide/formoterol) may be more effective than formoterol given alone
in treating patients with acute asthma who initially show
no response to 2-agonist therapy. The present study was
designed to compare the efficacy of
budesonide/formoterol with that of formoterol for the treatment of patients
with acute asthma who had evidence of relative
refractoriness to the administration of a short-acting 2-agonist.
Patients and methods
Patients
Patients aged 12 years presenting with acute asthma were
recruited from a total of 8 centres in Argentina, Mexico
and South Africa. All patients were required to have
asthma, as defined by the American Thoracic Society
criteria (including symptoms of wheeze, episodic cough, and
dyspnea) [12], with a pre-bronchodilator forced
expiratory volume in 1 second (FEV1; measured on arrival in the
Formoterol (n = 57) Budesonide/formoterol (n = 58)
All values are presented as absolute numbers or as means, except asthma duration, for which the median is given. aDose of inhaled corticosteroid
(budesonide equivalents) (...truncated)