Smoking
Conditions
Keywords
smokers, airway blood flow, fluticasone, echocardiogram
Brief summary
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
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).
Interventions
PROCEDUREechocardiogram plus albuterol
participants will performed echocardiogram before and 15 minutes after inhaled albuterol
PROCEDUREairway blood flow plus albuterol
participants will performed echocardiogram before and 15 minutes after inhaled albuterol
DRUGFluticasone propionate
participant will be received a 4-week course of inhaled fluticasone (220 μg fluticasone twice a day administered as a MDI using a spacer)
DRUGplacebo
participant will be received a 4-week course of identically appearing placebo (2 puffs twice a day via spacer).
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Airway Blood Flow | before and 15 minutes after albuterol inhalation | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Echocardiogram | MPAP before and 15 minutes after albuterol inhalation in smokers vs non-smokers | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Smokers echocardiogram: participants will performed echocardiogram before and 15 minutes after inhaled albuterol
airway blood flow: participants will performed echocardiogram before and 15 minutes after inhaled albuterol | 16 |
| Non-smokers echocardiogram: participants will performed echocardiogram before and 15 minutes after inhaled albuterol
airway blood flow: participants will performed echocardiogram before and 15 minutes after inhaled albuterol | 15 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Non-smokers | 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 | 16 Participants | 31 Participants |
| Age, Continuous | 44.7 years STANDARD_DEVIATION 2 | 47.6 years STANDARD_DEVIATION 2 | 46.2 years STANDARD_DEVIATION 2 |
| Gender Female | 9 Participants | 10 Participants | 19 Participants |
| Gender Male | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
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
Time frame: before and 15 minutes after albuterol inhalation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Smokers | Airway Blood Flow | 2.13 ΔQaw (ul/min/ml) | Standard Error 2.52 |
| Non-smokers | Airway Blood Flow | 13.05 ΔQaw (ul/min/ml) | Standard Error 1.22 |
Secondary
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
Time frame: MPAP before and 15 minutes after albuterol inhalation in smokers vs non-smokers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Smokers | Echocardiogram | -7.70 ΔMPAP (mmHg) | Standard Error 1.37 |
| Non-smokers | Echocardiogram | -9.04 ΔMPAP (mmHg) | Standard Error 0.74 |