Participants returned for V2 up to 4 weeks from enrollment visit, fasting. They came in the morning after 8 hours of fasting and refraining from nicotine products. Diastolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.

Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge heart rate measured supine, after 10 minutes rest from blood pressure monitor (dinamap). The post challenge heart rates were recorded 15-20 minutes post end of exposure to smoking or vaping challenge completion or in the case of controls after a 10 minute break.

Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break.

Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge ultrasound of brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break. The FMD protocol includes measuring % change in resting diameter after 60-90 seconds post fore-arm cuff occlusion release.

Expressed as a percentage of beats (supine recordings had be 5 minutes or longer to be valid). We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 1-2 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break.

Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls it was repeated after a 10 minute break.

We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability standing ratio was assessed pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break. Ratio between maximal heart rate after abrupt standing from a supine position and the subsequent lowest heart rate value within 40 seconds of peak.

maximum amount of air that the subject can forcibly expel during the first second following maximal inhalation, expressed as a percentage of the predicted normal values in the population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Amount of air that can be forcibly exhaled after taking the deepest breath possible expressed as a predicted percentage from the normal population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

The post challenge spirometry was recorded <15 minutes post end of exposure. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Participants attended Visit 2 (1-4 weeks after enrollment visit). They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge FeNO was obtained sitting and repeated within 15 minutes after smoking/vaping challenge.

Blood Pressure measured using the oscillometric technique before an acute exposure challenge following standardized protocol. After resting supine for 10 minutes blood pressure was measured on both arms and the average of the last two values was used.

Forced Vital Capacity is a measure of how much air can be exhaled forcefully obtained by spirometry pre acute exposure challenge.

Fractional Exhaled Nitric Oxide is a measure of airway inflammation measured before an acute exposure challenge.

Root mean square of standard deviation of rr intervals. Obtained fasting and refraining from nicotine exposure using the Sphymocor system. We used 10 or more minutes of supine data to derive heart rate variability measures.

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 was obtained as a measure of chronic exposure.

An ETT to determine exercise capacity will be completed as a measure of chronic exposure. Peak metabolic equivalents (METs, 1 MET=3.5 ml O2 uptake/kg body weight/minute) were determined at all exercise stages, peak exercise, and 1-minute post-exercise.

During V2, Diastolic Blood Pressure was measured using the oscillometric technique before an acute exposure challenge following a standardized protocol. After resting supine for 10 minutes blood pressure was measured on both arms and the average of the last two values was used. Participants attended v2 in the morning, fasting and refraining from nicotine products for at least 8 hours.

Peak RPP was calculated by multiplying maximun heart rate during exercise by systolic blood pressure as a reliable assessment of cardiac workload

Measure of maximal exercise capacity adjusted for age, calculated as max heart rate during treadmill divided by (220 minus the participant's age in yrs)

Difference in heart rate 60 seconds post treadmill minus maximal heart rate during treadmill..

< 100 cigarettes in lifetime, none for > 5 years; < 3 E-cig usage in lifetime

Total of all reporting groups

392 from Madison and 3 from Milwaukee, Wisconsin, USA

Exhaled CO concentration at final visit after 8 hours refraining from smoking or vaping

Serum Nicotine concentration at V2 after 8 hours of refraining from use of nicotine products.

For these assays, the minimum value was coded as 1.99 when the concentration was below the threshold of detection (<2 ng/ml).

Serum Cotinine concentration at V2 after 8 hours of refraining from use of nicotine products.

For these assays, the minimum value was coded as 1.99 when the concentration was below the threshold of detection (<2 ng/ml).

E-cig usage >/= 5 days/week for last 3 months

E-Cigarettes: E-cigarette usage >/= 5 days/week

< 100 cigarettes in lifetime, none for > 5 years; < 3 E-cig usage in lifetime

FEV1 is a primary measure of pulmonary disease obtained by spirometry that will be assessed before and after an acute exposure challenge. These are per-challenge values

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.

Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting.. They came in the morning after 8 hours of fasting and refraining from nicotine products. Systolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw.

Participants returned for V2 up to 4 weeks from enrollment visit, fasting. They came in the morning after 8 hours of fasting and refraining from nicotine products. Diastolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw.

Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge heart rate measured supine, after 10 minutes rest from blood pressure monitor (dinamap). The post challenge heart rates were recorded 15-20 minutes post end of exposure to smoking or vaping challenge completion or in the case of controls after a 10 minute break.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw.

Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw.

Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge ultrasound of brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break. The FMD protocol includes measuring % change in resting diameter after 60-90 seconds post fore-arm cuff occlusion release.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw.

Expressed as a percentage of beats (supine recordings had be 5 minutes or longer to be valid). We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 1-2 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some participants pre or post challenge due to poor ECG signals (noise) or frequent premature ventricular contractions did not have a usable 10 minute recording

Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls it was repeated after a 10 minute break.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some participants pre or post challenge due to poor ECG signals (noise) or frequent premature ventricular contractions did not have a usable 10 minute recording

We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability standing ratio was assessed pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break. Ratio between maximal heart rate after abrupt standing from a supine position and the subsequent lowest heart rate value within 40 seconds of peak.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some participants pre or post challenge due to poor ECG signals (noise) or frequent premature ventricular contractions did not have a usable recording

maximum amount of air that the subject can forcibly expel during the first second following maximal inhalation, expressed as a percentage of the predicted normal values in the population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some spirometry recordings were of poor quality and upon review by pulmonologist they were deemed not usable.

Amount of air that can be forcibly exhaled after taking the deepest breath possible expressed as a predicted percentage from the normal population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some spirometry recordings were of poor quality and upon review by pulmonologist they were deemed not usable.

The post challenge spirometry was recorded <15 minutes post end of exposure. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some spirometry recordings were of poor quality and upon review by pulmonologist they were deemed not usable.

Participants attended Visit 2 (1-4 weeks after enrollment visit). They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Some spirometry recordings were of poor quality and upon review by pulmonologist they were deemed not usable.

Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge FeNO was obtained sitting and repeated within 15 minutes after smoking/vaping challenge.

Not all controls (never users) were assessed post (after 10 minute break) due to time restrictions in personnel and one exclusive e-cigarette user was not assessed post due to a vaso-vagal response during blood draw. Other missing records were due to equipment malfunction or participant not being able to follow instructions to complete the test correctly.

Heart Rate pre-acute exposure challenge was obtained after resting supine for 10 minutes during V2 in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior.

Heart Rate Variability PNN50(%) measured before an exposure challenge. Participants attended visit 2 fasting and refraining from nicotine for at least 8 hours.

heart rate variability depends on a good quality electrocardiogram, and some participants due to noise, significant pauses, very slow heart rate or frequent premature ventricular contractions did not have usable records, hence lower number analyzed.

Blood Pressure measured using the oscillometric technique before an acute exposure challenge following standardized protocol. After resting supine for 10 minutes blood pressure was measured on both arms and the average of the last two values was used.

Forced Vital Capacity is a measure of how much air can be exhaled forcefully obtained by spirometry pre acute exposure challenge.

Fractional Exhaled Nitric Oxide is a measure of airway inflammation measured before an acute exposure challenge.

Root mean square of standard deviation of rr intervals. Obtained fasting and refraining from nicotine exposure using the Sphymocor system. We used 10 or more minutes of supine data to derive heart rate variability measures.

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 was obtained as a measure of chronic exposure.

An ETT to determine exercise capacity will be completed as a measure of chronic exposure. Peak metabolic equivalents (METs, 1 MET=3.5 ml O2 uptake/kg body weight/minute) were determined at all exercise stages, peak exercise, and 1-minute post-exercise.