Conditions: Asthma
Keywords: Asthma, airway blood flow, budesonide, glucocorticosteroid.
Allocation: RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief summary:
Glucocorticosteroids recently have been shown to have non-genomic actions that are plasma membrane-mediated and do not require gene transcription and translation. One of these non-genomic effects is the inhibition of adrenergic agonist transport into airway vascular smooth muscle cells with an increase of adrenergic agonist concentrations at adrenergic receptor sites and enhance the physiological effects of endogenous adrenergic agonists (e.g. locally released norepinephrine from noradrenergic neurons) or exogenous adrenergic agonists (e.g. inhaled beta-adrenergic agonists).

Detailed description:
Inhaled glucocorticosteroids typically are not recommended for the treatment of acute asthma attacks. This practice is based on the fact that glucocorticosteroids by themselves do not cause rapid bronchodilation. However, the acute inhibition of adrenergic agonist disposal by the non-genomic action of glucocorticosteroids could lead to bronchial vasoconstriction by locally released norepinephrine thereby decongesting the airway wall, and potentiate the bronchodilator effect of a concomitantly administered beta-adrenergic agonist through the same mechanism. The purpose of this study is to assess the vasoconstrictive effects of single and repetitive high-dose budesonide inhalations in moderate to severe asthmatics who use inhaled glucocorticosteroids regularly. As a secondary endpoint, airway inflammation and airway function will also be measured with the expectation that acute improvements in airflow might be detectable as a result of airway decongestion, notably in subjects with moderately severe asthma who have lower baseline lung function.

Arms:
arm 1: asthmatic subject received different doses of inhaled budesonide in random other arm 2: asthmatic subject received different doses of inhaled budesonide in random other arm 3: asthmatic subject received different doses of inhaled budesonide in random other arm 4: asthmatic subject received inhaled placebo arm 5: asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes.

Interventions: intervention 1: Budesonide 360ug intervention 2: Budesonide 720ug intervention 3: Budesonide 1440ug intervention 4: Budesonide720ug 4 times intervention 5: Placebo
Intervention descriptions: intervention 1: A single inhaled dose of 360ug budesonide from a DPI. intervention 2: A single inhaled dose of 720ug budesonide from a DPI. intervention 3: A single dose of 1440ug of the budesonide from DPI. intervention 4: 720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes. intervention 5: A single inhaled dose of placebo from a DPI.

Protocol document: