Tobacco Abuse Smoke
Conditions
Keywords
smokers, inhaled corticosteroids, brachial flow, airway blood flow, albuterol, spirometry, endothelial dysfunction
Brief summary
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
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.
Interventions
DRUGFluticasone
220 ug twice a day for 3 weeks
DRUGPlacebo
Placebo for 3 weeks
Sponsors
GlaxoSmithKline
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo | 3 weeks treatment period of ICS or placebo | Airway Blood flow (Qaw) will be measured before and 15 minutes after albuterol inhalation (delta Qaw). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated Brachial Vasodilation (FMD% Peak Delta) | 3 weeks of treatment | Flow-mediated vasodilation response in the brachial artery will be measured before and 15 minutes.after albuterol inhalation |
Countries
United States
Participant flow
Pre-assignment details
17 Non-smokers were enrolled to provide baseline measures and did not receive any intervention or treatment
Participants by arm
| Arm | Count |
|---|---|
| Smokers 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.
Fluticasone: 220 ug twice a day administered as a metered dose inhaled (MDI) | 15 |
| Non-smokers this group served as controls for baseline data. No intervention or treatment were assigned to this group. | 17 |
| Total | 32 |
Baseline characteristics
| Characteristic | Smokers | Non-smokers | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 17 Participants | 32 Participants |
| Age, Continuous age | 44 years | 38 years | 42 years |
| Airway blood flow (Qaw) | 50.3 um/ml/ul STANDARD_DEVIATION 3.7 | 46.2 um/ml/ul STANDARD_DEVIATION 3.5 | 48.2 um/ml/ul STANDARD_DEVIATION 3.4 |
| Region of Enrollment United States | 15 participants | 17 participants | 32 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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).
Time frame: 3 weeks treatment period of ICS or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluticasone | Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo | 40.9 % change | Standard Error 7.3 |
| Placebo | Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo | 0.0 % change | Standard Error 3.2 |
Secondary
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
Time frame: 3 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluticasone | Flow-mediated Brachial Vasodilation (FMD% Peak Delta) | 3.9 % change | Standard Error 0.6 |
| Placebo | Flow-mediated Brachial Vasodilation (FMD% Peak Delta) | 4.8 % change | Standard Error 0.6 |