Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Airway Blood Flow (Qaw)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Twenty lifetime nonsmokers moderate or severe asthmatics; FEV1≥50 of predicted on the screening day
排除标准
- •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
研究组 & 干预措施
budesonide 360ug
asthmatic subject received different doses of inhaled budesonide in random other
干预措施: Budesonide 360ug (Drug)
budesonide 720ug
asthmatic subject received different doses of inhaled budesonide in random other
干预措施: Budesonide 720ug (Drug)
budesonide 1440ug
asthmatic subject received different doses of inhaled budesonide in random other
干预措施: Budesonide 1440ug (Drug)
placebo
asthmatic subject received inhaled placebo
干预措施: Budesonide720ug 4 times (Drug)
Budesonide720ug 4 times
asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes.
干预措施: Placebo (Drug)
结局指标
主要结局
Airway Blood Flow (Qaw)
时间窗: 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.
次要结局
- Forced Expiratory Volume in 1 Second (FEV1)(participant will be followed up to 6 hours after budesonide dose)
研究者
Eliana Mendes
University of Miami
University of Miami