Interactive Acute Smooth Muscle Effects of Salmeterol and Fluticasone in the Airway

Study Overview
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Brief Summary
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The addition of an inhaled long-acting beta-adrenergic agonist to an inhaled glucocorticosteroid improves disease control in persistent asthma. This observation has supported the use of long-acting beta-adrenergic agonist/glucocorticosteroid combination preparations for the management of asthma. Currently, salmeterol/fluticasone and formoterol/budesonide are available for clinical use. The long-term beneficial clinical effects of the two drug classes seem to be synergistic, and several mechanisms of glucocorticoid-beta-adrenergic agonist interactions involving gene transcription have been invoked to explain this phenomenon.This study, wish to address the question whether glucocorticoids can acutely potentiate the bronchodilator response to a long-acting beta-adrenergic agonist.We expect that in patients with asthma, the short-term bronchodilator effect of salmeterol is enhanced by the addition of fluticasone, which by itself has no short-term bronchodilator effect. To test this premise, we will assess the respective short-term effects of salmeterol (50 µg), fluticasone (250 µg), salmeterol/fluticasone (50/250 µg), and placebo/placebo on spirometric parameters. Airway Blood flow will also be measured to ensure that vasoconstriction does not occur.

Detailed Description
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Fourteen lifetime nonsmokers with a physician diagnosis of asthma will be recruited for the study. All subjects will be allowed to use short-acting beta-adrenergic agonists as rescue medication. Inclusion criteria: Males and females, 18 to 65 years of age. FEV1 60-85% 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 medications 2. Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance 4. Acute respiratory infection within four weeks prior to the study 5. Use, within two weeks prior to the study, of any anti-asthma medication not mentioned above

Official Title
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Interactive Acute Smooth Muscle Effects of Salmeterol and Fluticasone in the Airway

Conditions
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Asthma

Intervention / Treatment
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* Drug: fluticasone
* Drug: placebo inhalation
* Drug: Salmeterol
* Drug: fluticasone/salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18 to 65 years of age. FEV1 60-85% of predicted on the screening day. - Exclusion Criteria: 1. Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women. 2. Cardiovascular disease and/or use of cardiovascular medications 3. Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance 4. Acute respiratory infection within four weeks prior to the study 5. Use, within two weeks prior to the study, of any anti-asthma medication not mentioned above -

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fluticasone/salmeterol<br>participants were treated fluticasone/salmeterol, | Drug: fluticasone/salmeterol<br>* inhalation of 250 mcg of fluticasone combined with 50 mcg of salmeterol<br>* Other names: advair;|
| Experimental: salmeterol<br>participants were treated with salmeterol | Drug: Salmeterol<br>* 50 mcg salmeterol once<br>* Other names: serevent;|
| Experimental: fluticasone<br>participants were treated with fluticasone | Drug: fluticasone<br>* 220- mcg once<br>* Other names: flovent;|
| Placebo Comparator: placebo inhalation<br>participants were treated with placebo | Drug: placebo inhalation<br>* placebo inhalation once<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Change From Baseline in Airway Blood Flow (Qaw) |  | maximum change in Qaw within 240 minutes post drug inhalation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, corticosteroids, bronchodilator, airway blood flow