Airway and Pulmonary Vascular Endothelial Function in Healthy Smokers: Effect of Inhaled Glucocorticosteroid Treatment

Study Overview
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Brief Summary
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The purposes of the present proposal are to 1) compare inhaled albuterol-induced changes in airway blood flow (Qaw), and in CO and Ppas in healthy current smokers and lifetime non-smokers as an index of endothelial function in the airway and pulmonary circulations, 2) compare the results between smokers and non-smokers, and 3) determine the effect of a 4-week treatment with an ICS on albuterol responsiveness of Qaw and the echocardiographic parameters. With this protocol the Investigators will test the hypotheses that a) there is a correlation between airway and pulmonary vascular endothelial function within the current smoker and non-smoker groups, and b) ICS treatment improves airway and pulmonary vascular endothelial function in the current smoker group.

Detailed Description
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With this protocol the Investigators will test the hypotheses that a) there is a correlation between airway and pulmonary vascular endothelial function within the current smoker and non-smoker groups, and b) ICS treatment improves airway and pulmonary vascular endothelial function in the current smoker group. Fifteen healthy current smokers with a >10 pack-year history of smoking and 15 healthy never-smokers will be enrolled. Males and females between 25 and 75 years of age will be recruited There will be 1-4 visits to the laboratory (one for non-smokers, 4 for smokers). All subjects will have the first visit. Current smokers will have 3 additional visits. Current smokers will be asked not to smoke before coming to the laboratory on the 3 study days. All subjects will be instructed to abstain from ingesting alcoholic beverages, coffee or caffeinated drinks for at least 12 hours the night before each study day. The subjects will also be instructed not to use PDE5 inhibitors for 24 hours before coming to the laboratory. On each study day, the protocol will start at the same time (in the morning).

Official Title
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Airway and Pulmonary Vascular Endothelial Function in Healthy Smokers: Effect of Inhaled Glucocorticosteroid Treatment

Conditions
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Smoking

Intervention / Treatment
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* Procedure: echocardiogram plus albuterol
* Procedure: airway blood flow plus albuterol
* Drug: Fluticasone propionate
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fifteen healthy current smokers with a >10 pack-year history of smoking and 15 healthy never-smokers will be enrolled. Males and females between 25 and 75 years of age will be recruited. 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 Subjects with known beta-adrenergic agonist intolerance A physician diagnosis of chronic airway disease (asthma, COPD, bronchiectasis, cystic fibrosis) Acute respiratory infection within four weeks prior to the study Use of any airway medication Abnormal pulmonary function

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: smokers<br>participants with smoking history ( > 10 pack/year) will be enrolled and perform airway blood flow and echocardiogram before and 15 minutes after albuterol inhalation | Procedure: echocardiogram plus albuterol<br>* participants will performed echocardiogram before and 15 minutes after inhaled albuterol<br>Procedure: airway blood flow plus albuterol<br>* participants will performed echocardiogram before and 15 minutes after inhaled albuterol<br>* Other names: Qaw;Drug: Fluticasone propionate<br>* participant will be received a 4-week course of inhaled fluticasone (220 μg fluticasone twice a day administered as a MDI using a spacer)<br>Drug: placebo<br>* participant will be received a 4-week course of identically appearing placebo (2 puffs twice a day via spacer).<br>|
| Experimental: non-smokers<br>healthy life-time non smokers will be enrolled and perform airway blood flow and echocardiogram before and 15 minutes after albuterol inhalation | Procedure: echocardiogram plus albuterol<br>* participants will performed echocardiogram before and 15 minutes after inhaled albuterol<br>Procedure: airway blood flow plus albuterol<br>* participants will performed echocardiogram before and 15 minutes after inhaled albuterol<br>* Other names: Qaw;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway Blood Flow | compare inhaled albuterol-induced changes in airway blood flow (ΔQaw) in healthy current smokers and lifetime non-smokers as an index of endothelial function in the airway circulation and to compare the results between smokers and non-smokers | before and 15 minutes after albuterol inhalation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiogram | to compare inhaled albuterol-induced changes in echocardiogram measuring mean pulmonary artery pressure (MPAP)in healthy current smokers and lifetime non-smokers as an index of endothelial function in the pulmonary circulation and to compare the results between smokers and non-smokers | MPAP before and 15 minutes after albuterol inhalation in smokers vs non-smokers | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smokers, airway blood flow, fluticasone, echocardiogram