Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study

BACKGROUND: The long-acting β(2)-agonist (LABA) formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma. METHODS: In this randomised, double-blind, placebo-controlled, cross-over study, 32 patients with asthma underwent a methacholine provocation test leading to a fall in forced expiratory volume in 1 second (FEV(1)) of ≥30% at enrolment (Visit 1) and three subsequent study visits (Visits 2–4). Immediately after each provocation at Visits 2–4, patients received one of three test treatments: one inhalation of budesonide/formoterol 160/4.5 μg (via Turbuhaler(®)), two inhalations of salbutamol 100 μg (via a pressurised metered-dose inhaler [pMDI]) or placebo. All patients received each of the test treatments in a randomised order, after separate methacholine provocations. The effect of treatment on FEV(1 )and breathlessness (using the Borg scale) was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment. RESULTS: Following methacholine provocation, Borg score increased from a baseline value of below 0.5 to 3.03, 3.31 and 3.50 before treatment with budesonide/formoterol, salbutamol and placebo, respectively. Budesonide/formoterol and salbutamol reversed methacholine-induced dyspnoea (breathlessness) rapidly. At 1 minute after inhalation, statistically significant decreases in Borg score were observed for budesonide/formoterol and salbutamol (p = 0.0233 and p < 0.0001, respectively, versus placebo), with similar rapid increases in FEV(1 )(both active treatments p < 0.0001 versus placebo). The median time to 50% recovery in Borg score after methacholine provocation was 3 minutes with budesonide/formoterol, 2 minutes with salbutamol and 10 minutes with placebo. All treatments and procedures were well tolerated. CONCLUSION: Single doses of budesonide/formoterol and salbutamol both provided rapid relief of dyspnoea and reversal of severe airway obstruction in patients with asthma with experimentally induced bronchoconstriction. The perception of relief, as confirmed by objective lung function assessment, provides evidence that budesonide/formoterol can be used as reliever medication in asthma

Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

<p>Abstract</p> <p>Background</p> <p>The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β₂-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, <b><it>flutiform</it></b>^®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol.</p> <p>Methods</p> <p>Patients aged ≥ 18 years (N = 202) with mild-to-moderate–severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4–10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV₁), at week 12.</p> <p>Results</p> <p>Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV₁at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV₁, change from pre-dose FEV₁at baseline to 2-hour post-dose FEV₁at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol.</p> <p>Conclusions</p> <p>The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00476073">NCT00476073</a></p

Relief of dyspnoea by beta(2)-agonists after methacholine-induced bronchoconstriction

AbstractVirtually all asthma patients use bronchodilators. Formoterol and salbutamol have a rapid onset of bronchodilating effect, whereas salmeterol acts slower. We studied the onset of improvement of dyspnoea sensation after inhalation with these bronchodilators and placebo to reverse a methacholine-induced bronchoconstriction as a model for an acute asthma attack.Seventeen patients with asthma completed this randomised, double-blind, crossover, double-dummy study. On 4 test days, forced expiratory volume in 1s (FEV1) and Borg score were recorded and patients were challenged with methacholine until FEV1 fell with ⩾30% of baseline value. Thereafter, formoterol 12μg via Turbuhaler®, salbutamol 50μg via Turbuhaler®, salmeterol 50μg via Diskhaler™, or placebo was inhaled. FEV1 and Borg scores were assessed during the following 60min.The first sensed improvement of Borg score was significantly (P<0.05) faster achieved with formoterol (geometric mean (Gmean) (range) 1.5 (1–40)min) and salbutamol 1.8 (1–10)min than with salmeterol 4.5 (1–30)min and placebo 3.4 (1–40)min.The Borg score returned significantly faster to the baseline value with formoterol, salbutamol, and salmeterol (Gmean time 13.8 (1–75), 13.4 (1–60), and 18.0 (1–75)min, respectively) than with placebo (33.6 (1–75min).Formoterol and salbutamol act significantly faster than salmeterol in relieving dyspnoea induced by methacholine-induced bronchoconstriction, in patients with asthma