Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Study Overview
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Brief Summary
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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
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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.

Official Title
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Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Conditions
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Asthma

Intervention / Treatment
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* Drug: Budesonide 360ug
* Drug: Budesonide 720ug
* Drug: Budesonide 1440ug
* Drug: Budesonide720ug 4 times
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: budesonide 360ug<br>asthmatic subject received different doses of inhaled budesonide in random other | Drug: Budesonide 360ug<br>* A single inhaled dose of 360ug budesonide from a DPI.<br>* Other names: Pulmicort Flexhaler;|
| Experimental: budesonide 720ug<br>asthmatic subject received different doses of inhaled budesonide in random other | Drug: Budesonide 720ug<br>* A single inhaled dose of 720ug budesonide from a DPI.<br>* Other names: Pulmicort Flexhaler;|
| Experimental: budesonide 1440ug<br>asthmatic subject received different doses of inhaled budesonide in random other | Drug: Budesonide 1440ug<br>* A single dose of 1440ug of the budesonide from DPI.<br>* Other names: Pulmicort Flexhaler;|
| Placebo Comparator: placebo<br>asthmatic subject received inhaled placebo | Drug: Budesonide720ug 4 times<br>* 720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.<br>* Other names: Pulmicort Flexhaler;|
| Experimental: Budesonide720ug 4 times<br>asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes. | Drug: Placebo<br>* A single inhaled dose of placebo from a DPI.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway Blood Flow (Qaw) | 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. | participants will be followed for 6 hours after budesonide dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) | 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. | participant will be followed up to 6 hours after budesonide dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, airway blood flow, budesonide, glucocorticosteroid.