Trial Outcomes & Findings for Acute Effects of E-Cigarette Aerosol Inhalation (NCT NCT03479203)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

31 participants

Primary outcome timeframe

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

Results posted on

2024-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	31
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Acute Effects of E-Cigarette Aerosol Inhalation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy, Non-Smokers n=31 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=31 Participants 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.
Inflammatory Blood-Based Biomarkers	5 fold change Standard Deviation 0.5

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=30 Participants 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.
Acute Change in Aortic Pulse Wave Velocity Post-vaping	0.19 Meters per second Standard Deviation 0.20

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=30 Participants 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.
Change in Femoral Artery Flow-Mediated Dilation Post-Vaping	-3.20 percentage of change in cross-sectional Standard Deviation 0.90

PRIMARY outcome

Timeframe: 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.)

Transit time of desaturated capillary blood from tissue to the imaging location after e-cigarette vaping

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=30 Participants 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.
Change in Washout Time Post-Vaping	-1.50 Seconds Standard Deviation 0.30

PRIMARY outcome

Timeframe: 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.)

Tissue oxygen resaturation rate after e-cigarette vaping.

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=30 Participants 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.
Change in Upslope Post-Vaping	0 percentage of oxygen saturation/sec Standard Deviation 0.20

PRIMARY outcome

Timeframe: 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.)

Degree of overcompensatory effect post-vaping in the supply of oxygen after ischemia.

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=30 Participants 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.
Change in Overshoot Post-Vaping	10 percentage of oxygen saturation/sec Standard Deviation 2.0

PRIMARY outcome

Timeframe: 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.)

Rate of increase in blood flow velocity in the superior sagittal sinus from intermittent volitional apnea.

Outcome measures

Outcome measures
Measure	Healthy, Non-Smokers n=30 Participants 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.
Change in Breath Hold Index Post-Vaping	-0.02 Centimeters per Seconds Squared Standard Deviation 0.02

Adverse Events

Healthy, Non-Smokers

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Felix W.Wehrli, PhD

University of Pennsylvania

Phone: 215-662-7951

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place