E-Cigarette Effects on Markers of Cardiovascular and Pulmonary Disease
Study Details
Study Description
Brief Summary
This study is designed to enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. Participants will be enrolled in 3 groups: exclusive e-cigarette users, exclusive cigarette smokers, and a control group of never-users. Participants can expect up to 4 weeks of study participation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
E-cigarette use is increasing rapidly in the United States, especially amongst youth, underscoring the vital need to improve understanding of its health risks. Relevant data could inform policy, guide public health and clinical intervention efforts, and inform individuals who might use or who are using this product. This research will significantly enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. 3 different "use-groups" of participants will be enrolled: exclusive e-cigarette users (n=165), exclusive cigarette smokers (n=165), and a "control" group of never-users (n=110). These groups reflect the primary decisions that people can make regarding their future tobacco use: to continue to smoke cigarettes, to switch to e-cigarettes, or to avoid tobacco use entirely. It is essential that smokers and health care providers have accurate information on the health effect of these choices.
[Additionally,100 participants will be invited to be part of an epigenetics sub-study (50 E-cig users, 25 smokers and 25 controls), prior to smoking, an additional 16 ml of blood will be collected in Vacutainer CPTTM cell separation tubes for PBMC Isolation containing sodium citrate.]
Product use will be related to well-validated biomarkers that sensitively and reproducibly reflect mechanisms, injury, and/or future risk related to cardiovascular or pulmonary disease. Biomarkers will be related to: 1) acute product use in the laboratory (exposure challenges), 2) lifetime history of product use, and/or 3) real-time measures of product use in participants' daily lives. The primary cardiovascular biomarkers are brachial artery flow-mediated dilation (a measure of endothelial function) and carotid intima-media thickness, a measure of subclinical arterial injury and atherosclerosis. The primary pulmonary disease biomarkers will be measures of lung volumes and flow rates (FEV1, FVC, FEV1/FVC, FEF25-75) obtained by spirometry. Treadmill exercise stress testing will be performed (to assess aerobic fitness), electrocardiography (to measure heart rate variability, HRV), and measure heart rate, blood pressure, lipids, HgbA1c, and inflammation/oxidation markers (leukocyte count, C-reactive protein, urinary F2 isoprostanes and exhaled nitric oxide). This research will show how product use-groups differ in response to acute product use and long-term use as they are related to key cardiovascular and pulmonary biomarkers. Objective measures of product use include exhaled CO and plasma nicotine/cotinine and urinary nicotine/cotinine concentrations. History of product use within use-groups will be related to biomarker status.
The proposed research will yield vital and comprehensive data regarding product use, subclinical arterial injury, atherosclerosis burden, arterial and pulmonary function, cardiac and aerobic fitness, cardiac autonomic regulation, systemic and pulmonary inflammation, and oxidative stress, as well as other key outcomes. These data will serve as a foundation for future longitudinal investigations of e-cigarette health effects and will inform public policy decisions, clinical intervention, and patient guidance regarding e-cigarettes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Exclusive Smokers Smokes Daily; >/= 5 cigarettes/day for last 6 months |
Behavioral: Cigarettes
smokes daily
|
| Exclusive E-Cig users E-cig usage >/= 5 days/week for last 3 months |
Behavioral: E-Cigarettes
E-cigarette usage >/= 5 days/week
Other Names:
|
| Never users < 100 cigarettes in lifetime, none for > 5 years; < 3 E-cig usage in lifetime |
Outcome Measures
Primary Outcome Measures
- Brachial Artery Flow-Mediated Dilation (FMD) [up to 4 weeks]
Brachial Artery Flow-Mediated Dilation is a primary cardiovascular biomarker and a measure of endothelial function that will be assessed before and after an acute exposure challenge.
- Forced Expiratory Volume (FEV1) [up to 4 weeks]
FEV1 is a primary measure of pulmonary disease obtained by spirometry that will be assessed before and after an acute exposure challenge.
- Carotid Intima-Media Thickness (IMT) [up to 4 weeks]
Carotid Intima-Media Thickness is a cardiovascular biomarker and a measure of sub-clinical arterial injury and atherosclerosis as a result of chronic exposure. IMT will be measured via ultrasonography.
Secondary Outcome Measures
- Heart Rate (HR) [up to 4 weeks]
Heart Rate will be measured in response to an acute exposure challenge.
- Heart Rate Variability (HRV) [up to 4 weeks]
Heart Rate Variability will be measured before and after an acute exposure challenge.
- Systolic, Diastolic and Mean Blood Pressure (BP) [up to 4 weeks]
Blood Pressure will be measured using the oscillometric technique before and after an acute exposure challenge.
- Forced Vital Capacity (FVC) [up to 4 weeks]
Forced Vital Capacity is a measure of how much air can be exhaled forcefully. It will be obtained by spirometry pre and post an acute exposure challenge.
- Fractional Exhaled Nitric Oxide (FeNO) [up to 4 weeks]
Fractional Exhaled Nitric Oxide is a measure of airway inflammation and changes will be measured in response to an acute exposure challenge.
- Carotid Artery Wall Echogenicity [up to 4 weeks]
Carotid wall ultrasound tissue characterization to assess arterial wall echogenicity (brightness) by gray scale median pixel density, and texture features using variation measures and second-order pixel density analysis (entropy and contrast) will be evaluated as a measure of chronic exposure.
- Arterial Pulse Wave Analysis (PWA) [up to 4 weeks]
Analysis of radial pressure wave forms allows for non-invasive estimation of central aortic pressures, accounting for pressure amplification and the amplitude of the arterial pulse wave as it moves through arteries away from the heart. The Atcor Sphygmacor system can derive central aortic pressures from radial tracings using a validated transfer function. This computation is performed using the pulse wave analysis (PWA) mode. Pulse Wave Analysis via radial tonometry will be completed as a measure of chronic exposure.
- Electrocardiogram (ECG) Analysis [up to 4 weeks]
A 12 lead resting ECG will be completed assessing P axis, QRS axis, T axis, P-Q interval, QRS complex voltage, QT and QTc intervals, and Minnesota codes as measures of chronic exposure.
- Exercise Treadmill stress Test (ETT) [up to 4 weeks]
An ETT to determine exercise capacity will be completed as a measure of chronic exposure.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
able to read and write English
-
no plans to quit smoking and/or e-cig use in the next month
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not using cigars/smokeless/snus tobacco >/= 1 time per week
-
having a stable pattern of current product use
-
able to walk at least 2 blocks without assistance or stopping
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Specific to Exclusive Smokers:
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smokes daily
-
/= 5 cigs/day for last 6 months
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< 3 uses E-cigs in lifetime
-
/= 5 ppm carbon monoxide (CO)
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Cotinine > 100 ng/ml
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Specific to Exclusive E-cig users:
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</= 2 days per month cigarette use for last 6 months
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/= 5 days per week E-cig use for last 3 months
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</= 4 ppm CO
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Cotinine > 100 ng/ml
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Specific to Never-users
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< 100 cigarettes in a lifetime, none for > 5 years
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< 3 E-cig uses in a lifetime
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</= 4 ppm CO
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Continine < 100 ng/ml
Exclusion Criteria:
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current use of a smoking cessation medication
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women who are pregnant or plan to get pregnant in the coming month
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women who might be pregnant
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incarcerated individuals
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history of sarcoidosis in past 5 years, or active interstitial lung/pulmonary fibrosis
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history of positive COVID-19 test
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Wisconsin | Madison | Wisconsin | United States | 53792 |
Sponsors and Collaborators
- University of Wisconsin, Madison
- National Institutes of Health (NIH)
- National Heart, Lung, and Blood Institute (NHLBI)
- University of Wisconsin Center for Tobacco Research and Intervention
Investigators
- Principal Investigator: James H Stein, MD, University of Wisconsin, Madison
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-1090
- 1R01HL139331-01
- Protocol Version 4/26/2021
- A534225
- SMPH\MEDICINE\CARDIOLOGY