Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide
| Status: | Completed |
|---|---|
| Conditions: | Asthma |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 3/1/2014 |
| Start Date: | July 2008 |
| End Date: | January 2011 |
| Contact: | Eliana Mendes, MD |
| Email: | emendes@med.miami.edu |
| Phone: | (305) 243-2568 |
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 noraderenergic neurons) or exogenous adrenergic
agonists (e.g. inhaled beta-adrenergic agonists).
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 noraderenergic neurons) or exogenous adrenergic
agonists (e.g. inhaled beta-adrenergic agonists).
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.
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.
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
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Miami, Florida 33136
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