Biochemical Markers, Endothelial Dysfunction
Conditions
Keywords
Inflammation
Brief summary
This study comprises a portion of a larger study designed to compare results of vascular function in non-smokers to vascular function in healthy smokers chronically exposed to nicotinized electronic cigarette aerosol versus conventional cigarettes.
Detailed description
Here, we 1) investigate the acute effects of non-nicotinized e-cigarette aerosol inhalation in nonsmokers in terms of blood-based markers of inflammation and oxidative stress, and 2) evaluate their association with hemodynamic-metabolic MRI parameters quantifying peripheral vascular reactivity, cerebrovascular reactivity, and aortic stiffness.
Interventions
DRUGElectronic Cigarette Aerosol
16 two-second-long puffs from a non-nicotinized electronic cigarette.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
• BMI of 18.5 - 30
Exclusion criteria
* Cancer * HIV * Mental illness * Overt cardio- or neurovascular disease (prior heart attack, stroke, transient ischemic attacks) * Serious arrhythmias * Bronchospastic disease * Upper respiratory tract infection within the past six weeks * Chronic medication or antibiotics * Claustrophobia / contraindications for MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Blood-Based Biomarkers | Participant blood draws occurred at two time points: 1) pre-vaping, 2) 120 minutes post-vaping. Inflammation index is calculated from the fold change in biomarker values over pre-vaping values | Post-vaping inflammation monitored by changes in an integrated cluster of blood-based biomarkers from serum/plasma of non-smoking healthy participants quantified at 0 and 120 min post-inhalation. The cluster consisted of: CRP, sICAM-1 in serum and HMGB1, ASC in plasma assayed using ELISA and quantified using absorbance-concentration curves generated by the manufacturers' standards; nitric oxide metabolites (nitrate + nitrite, NOx) in serum assayed with a nitrate/nitrite kit using a colorimetric standard provided by the manufacturer; reactive oxygen species (ROS) was quantified by using immortalized human pulmonary microvascular endothelial cells plated, prepared with serum, labeled with ROS dye and imaged confocal fluorescence microscopy. The outcome measure was expressed as fold increase over pre-vaping values. |
| Acute Change in Aortic Pulse Wave Velocity Post-vaping | PWV calculation occurred at two time points: 1) pre-vaping, 2) Fifteen minutes post-vaping. | Central arterial stiffness was assessed using aortic pulse-wave velocity (PWV), a biomarker of aortic stiffness calculated by measuring the velocity of a pulse wave between two points in the same artery. A higher aortic pulse wave velocity equates to a stiffer aorta. In each participant, aortic PWV was quantified, pre- and post-vaping, by dividing the path length of the aortic arch determined from a oblique sagittal image, by the transit time of the pulse pressure wave. Measurements obtained pre-vaping were compared to those obtained post-vaping. |
| Change in Femoral Artery Flow-Mediated Dilation Post-Vaping | Flow mediated dilation calculation occurred at two time points: 1) pre-vaping, 2) 40 minutes post-vaping. | Degree of dilation (% change in cross-sectional area) of femoral artery during hyperemia (the transient increase in blood flow velocity) after e-cigarette vaping as compared to before e-cigarette vaping. |
| Change in Washout Time Post-Vaping | Washout time calculation occurred at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping | Transit time of desaturated capillary blood from tissue to the imaging location after e-cigarette vaping |
| Change in Upslope Post-Vaping | Upslope was calculated at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping | Tissue oxygen resaturation rate after e-cigarette vaping. |
| Change in Overshoot Post-Vaping | Overshoot was calculated at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping. | Degree of overcompensatory effect post-vaping in the supply of oxygen after ischemia. |
| Change in Breath Hold Index Post-Vaping | Breath hold index was calculated at two time points: 1) pre-vaping, 2) five minutes post-vaping. | Rate of increase in blood flow velocity in the superior sagittal sinus from intermittent volitional apnea. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy, Non-Smokers Men and women between the ages of 18 and 35 years with no history of smoking, systemic disease, recent respiratory infection or chronic intake of medication. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Healthy, Non-Smokers |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Acute Change in Aortic Pulse Wave Velocity Post-vaping
Central arterial stiffness was assessed using aortic pulse-wave velocity (PWV), a biomarker of aortic stiffness calculated by measuring the velocity of a pulse wave between two points in the same artery. A higher aortic pulse wave velocity equates to a stiffer aorta. In each participant, aortic PWV was quantified, pre- and post-vaping, by dividing the path length of the aortic arch determined from a oblique sagittal image, by the transit time of the pulse pressure wave. Measurements obtained pre-vaping were compared to those obtained post-vaping.
Time frame: PWV calculation occurred at two time points: 1) pre-vaping, 2) Fifteen minutes post-vaping.
Population: Participants\* underwent an intervention which consisted of 16 3-second inhalations from a vaping device delivering non-nicotinized electronic cigarette aerosol. A quantitative magnetic resonance imaging scan was conducted pre- and post-vaping. Differences in aortic PWV before versus after e-cigarette vaping were assessed.~\*One participant not analyzed due to discomfort during the scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Acute Change in Aortic Pulse Wave Velocity Post-vaping | 0.19 Meters per second | Standard Deviation 0.2 |
Primary
Change in Breath Hold Index Post-Vaping
Rate of increase in blood flow velocity in the superior sagittal sinus from intermittent volitional apnea.
Time frame: Breath hold index was calculated at two time points: 1) pre-vaping, 2) five minutes post-vaping.
Population: Participants underwent an intervention which consisted of 16 3-second inhalations from a vaping device delivering non-nicotinized electronic cigarette aerosol. A 50 minute quantitative magnetic resonance imaging protocol was conducted pre- and post-vaping. (One participant not analyzed due discomfort with the cuff occlusion portion of the protocol.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Change in Breath Hold Index Post-Vaping | -0.02 Centimeters per Seconds Squared | Standard Deviation 0.02 |
Primary
Change in Femoral Artery Flow-Mediated Dilation Post-Vaping
Degree of dilation (% change in cross-sectional area) of femoral artery during hyperemia (the transient increase in blood flow velocity) after e-cigarette vaping as compared to before e-cigarette vaping.
Time frame: Flow mediated dilation calculation occurred at two time points: 1) pre-vaping, 2) 40 minutes post-vaping.
Population: Participants\* underwent an intervention which consisted of 16 3-second inhalations from a vaping device delivering non-nicotinized electronic cigarette aerosol. A quantitative magnetic resonance imaging scan was conducted pre- and post-vaping. Differences in flow mediated dilation before versus after e-cigarette vaping were assessed.~\*One participant not analyzed due to discomfort during the scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Change in Femoral Artery Flow-Mediated Dilation Post-Vaping | -3.20 percentage of change in cross-sectional | Standard Deviation 0.9 |
Primary
Change in Overshoot Post-Vaping
Degree of overcompensatory effect post-vaping in the supply of oxygen after ischemia.
Time frame: Overshoot was calculated at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping.
Population: Participants underwent an intervention which consisted of 16 3-second inhalations from a vaping device delivering non-nicotinized electronic cigarette aerosol. A 50 minute quantitative magnetic resonance imaging protocol was conducted pre- and immediately post-vaping. (One participant not analyzed due discomfort with the cuff occlusion portion of the protocol.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Change in Overshoot Post-Vaping | 10 percentage of oxygen saturation/sec | Standard Deviation 2 |
Primary
Change in Upslope Post-Vaping
Tissue oxygen resaturation rate after e-cigarette vaping.
Time frame: Upslope was calculated at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping
Population: Participants underwent an intervention which consisted of 16 3-second inhalations from a vaping device delivering non-nicotinized electronic cigarette aerosol. A 50 minute quantitative magnetic resonance imaging protocol was conducted pre- and immediately post-vaping. (One participant not analyzed due discomfort with the cuff occlusion portion of the protocol.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Change in Upslope Post-Vaping | 0 percentage of oxygen saturation/sec | Standard Deviation 0.2 |
Primary
Change in Washout Time Post-Vaping
Transit time of desaturated capillary blood from tissue to the imaging location after e-cigarette vaping
Time frame: Washout time calculation occurred at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping
Population: Participants underwent an intervention which consisted of 16 3-second inhalations from a vaping device delivering non-nicotinized electronic cigarette aerosol. A 50 minute quantitative magnetic resonance imaging protocol was conducted pre- and immediately post-vaping. (One participant not analyzed due discomfort with the cuff occlusion portion of the protocol.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Change in Washout Time Post-Vaping | -1.50 Seconds | Standard Deviation 0.3 |
Primary
Inflammatory Blood-Based Biomarkers
Post-vaping inflammation monitored by changes in an integrated cluster of blood-based biomarkers from serum/plasma of non-smoking healthy participants quantified at 0 and 120 min post-inhalation. The cluster consisted of: CRP, sICAM-1 in serum and HMGB1, ASC in plasma assayed using ELISA and quantified using absorbance-concentration curves generated by the manufacturers' standards; nitric oxide metabolites (nitrate + nitrite, NOx) in serum assayed with a nitrate/nitrite kit using a colorimetric standard provided by the manufacturer; reactive oxygen species (ROS) was quantified by using immortalized human pulmonary microvascular endothelial cells plated, prepared with serum, labeled with ROS dye and imaged confocal fluorescence microscopy. The outcome measure was expressed as fold increase over pre-vaping values.
Time frame: Participant blood draws occurred at two time points: 1) pre-vaping, 2) 120 minutes post-vaping. Inflammation index is calculated from the fold change in biomarker values over pre-vaping values
Population: For each participant, the fold change is obtained as as logarithmic fold increases over pre-vaping values, as: log2(fold change) = log2(expression value(s) of post-vape biomarker) - log2(expression value(s) of pre-vape biomarker). Data are expressed as means ± SD (5 - 18 nanograms per milliliter range) and two-tailed paired t tests were used to determine statistical significance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy, Non-Smokers | Inflammatory Blood-Based Biomarkers | 5 fold change | Standard Deviation 0.5 |
Comparison: Blood assessed for C-reactive protein (CRP), soluble intercellular adhesion molecule (sICAM), the high mobility group box-1 (HMGB1), the NLRP3 inflammasome, and nitrates (NOx for nitric oxide) pre- and post-vaping. CRP, sICAM HMGB1 and NLRP3 is in ng/ml blood and NOx is in nanomol/ml. These numbers were weighted to obtain an inflammation index in blood. This index represents the fold increase over pre-vaping values.p-value: 0.0595% CI: [1, 6]t-test, 2 sided