Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Not Applicable

Completed

Conditions: Asthma

Interventions: Drug: Budesonide 1440ug
Drug: Placebo
Drug: Budesonide 720ug
Drug: Budesonide 360ug
Drug: Budesonide720ug 4 times

Registration Number: NCT01219738

Lead Sponsor: University of Miami

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Twenty lifetime nonsmokers moderate or severe asthmatics; FEV1≥50 of predicted on the screening day

Exclusion Criteria

Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women; Cardiovascular disease and/or use of cardiovascular medication; Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance; Acute respiratory infection and or acute exacerbation of asthma within four weeks prior to the study; Use of systemic glucocorticosteroids within 4 weeks prior to the study; Daily ICS dose (fluticasone or budesonide) > 500ug; Diabetes mellitus

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
budesonide 1440ug	Budesonide 1440ug	asthmatic subject received different doses of inhaled budesonide in random other
Budesonide720ug 4 times	Placebo	asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes.
budesonide 720ug	Budesonide 720ug	asthmatic subject received different doses of inhaled budesonide in random other
budesonide 360ug	Budesonide 360ug	asthmatic subject received different doses of inhaled budesonide in random other
placebo	Budesonide720ug 4 times	asthmatic subject received inhaled placebo

Primary Outcome Measures

Name	Time	Method
Airway Blood Flow (Qaw)	participants will be followed for 6 hours after budesonide dose	Qaw will be measured before and up to 6 hours after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

Secondary Outcome Measures

Name	Time	Method
Forced Expiratory Volume in 1 Second (FEV1)	participant will be followed up to 6 hours after budesonide dose	FEV1 will be measured before and up to 6 hours after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.