Conditions: Asthma
Keywords: Asthma Glucocorticoid Long-acting beta2-adrenoceptor Inhaled corticosteroids
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 10
Healthy volunteers: no

Brief summary:
To investigate a possible interaction between formoterol and budesonide on GR-translocation and to compare the effect of different doses of Symbicort (80/4.5 and 2x80/4.5 mcg) with the effect of budesonide (200 mcg and 800 mcg) on GR translocation, and to investigate the effect of the study drugs on exhaled NO (bronchial and alveolar fraction.

Detailed description:
Combination therapy with inhaled corticosteroids (ICS) and long-acting β(2)-adrenergic agonists (LABA) is reported to have superior effects on controlling asthma symptoms to ICS alone; however, there is no molecular-based evidence to explain the clinical effects. Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophage.

In a randomised, double-blind cross-over placebo-controlled 6-visit study, 10 patients with mild asthma were given placebo, formoterol (Oxis(®) 12 μg), budesonide (Pulmicort(®) 200 μg :BUD200, or 800 μg :BUD800), or budesonide/formoterol combination (Symbicort(®)) as a single 100/6 μg (SYM100) or double 200/12 μg (SYM200) dose. Sputum macrophages were separated by plate adhesion from induced sputum. GR binding to the glucocorticoid-response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA. mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by quantitative RT-PCR.

Arms:
arm 1: placebo arm 2: Oxis(®) 12 μg arm 3: Pulmicort(®) 200 μg arm 4: Pulmicort(®) 800 μg arm 5: single 100/6 μg SYM100 arm 6: double 200/12 μg SYM200

Interventions: intervention 1: Placebos intervention 2: Formoterol Inhalant Powder intervention 3: Budesonide Powder intervention 4: Budesonide and Formoterol Product
Intervention descriptions: intervention 1: Dry powder inhaler intervention 2: 12ug intervention 3: Inhaler intervention 4: Combination Inhaler, Symbicort

Protocol document: