Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers

Study Overview
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Brief Summary
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The hypothesis underlying the proposed study is that the blunted endothelium-dependent vasodilation seen in the airway of current smokers is also present in the brachial artery, and that the same inhaled corticosteroid (ICS) treatment regime that reversed endothelial function in the airway of current smokers will also restore endothelium-dependent relaxation in the brachial artery. Non-smokers will be used as controls and will not receive any intervention or treatment.

Detailed Description
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Cigarette smoking can lead to systemic endothelial dysfunction. Since the airway circulation is exposed to a high concentration of cigarette smoke constituents, we reasoned that airway vascular endothelial dysfunction could be present in healthy smokers without systemic endothelial dysfunction. The purpose of this study was to compare airway and systemic endothelial function and measure markers of systemic inflammation in lung-healthy current smokers. Since endothelial dysfunction in smokers has been related to systemic inflammation, we also investigated its response to an inhaled glucocorticosteroid (ICS). Vascular endothelial function was assessed in the airway by the airway blood-flow (Qaw) response to inhaled albuterol (ΔQaw) and in the extrapulmonary circulation by brachial arterial flow-mediated vasodilation (FMD). Venous blood was collected for C-reactive protein and IL-6. Qaw was measured with a noninvasive inhaled soluble gas uptake technique. The uptake of the gas from the anatomical deadspace reflecting airways perfused by the airway circulation was quantitated. Qaw was express as μL/min normalized for anatomical deadspace: μL/min/mL.

Official Title
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Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers

Conditions
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Tobacco Abuse Smoke

Intervention / Treatment
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* Drug: Fluticasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For both healthy non-smokers and healthy current smokers: normal spirometry Healthy current smokers: history of >10 pack-year smoking 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 or nitroglycerin 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. FEV1 < 80% of predicted and FEV1/FVC < 0.7. A body mass index > 30.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: smokers, Fluticasone first, then Placebo<br>The current smokers will be given a 3-week treatment course of inhaled fluticasone (220 ug fluticasone twice a day administered as a MDI) . The subjects and the investigators will be blinded to the random choice of inhaler. | Drug: Fluticasone<br>* 220 ug twice a day for 3 weeks<br>* Other names: flovent;Drug: Placebo<br>* Placebo for 3 weeks<br>* Other names: sugar pill;|
| Placebo Comparator: smokers Placebo first, then Fluticasone<br>The current smokers will be given a 3-week treatment course of inhaled placebo MDI. The subjects and the investigators will be blinded to the random choice of inhaler. | Drug: Fluticasone<br>* 220 ug twice a day for 3 weeks<br>* Other names: flovent;Drug: Placebo<br>* Placebo for 3 weeks<br>* Other names: sugar pill;|
| No Intervention: health non-smokers<br>The healthy non-smokers will have only visit 1 and no intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo | Airway Blood flow (Qaw) will be measured before and 15 minutes after albuterol inhalation (delta Qaw). | 3 weeks treatment period of ICS or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow-mediated Brachial Vasodilation (FMD% Peak Delta) | Flow-mediated vasodilation response in the brachial artery will be measured before and 15 minutes.after albuterol inhalation | 3 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smokers, inhaled corticosteroids, brachial flow, airway blood flow, albuterol, spirometry, endothelial dysfunction