Acute Effects of E-Cigarette Aerosol Inhalation

Endothelial Dysfunction Clinical Trial

Official title:

Acute and Long-term Effects of E-Cigarette Aerosol Inhalation on Biomarkers of Endothelial Function and Vascular Reactivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03479203
• Other study ID #: 828195
• Secondary ID: R01HL139358
• Status: Completed
• Phase: Early Phase 1
• Start date: May 22, 2018
• Est. completion date: August 31, 2022

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 31, 2022
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Biochemical Markers
• Endothelial Dysfunction
• Respiratory Aspiration

Intervention

Drug:
• Electronic Cigarette Aerosol
16 two-second-long puffs from a non-nicotinized electronic cigarette.

Locations

Country	Name	City	State
United States	University of Pennsylvania Perelman School of Medicine	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (8)

Caporale A, Langham MC, Guo W, Johncola A, Chatterjee S, Wehrli FW. Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI. Radiology. 2019 Oct;293(1):97-106. doi: 10.1148/radiol.2019190562. Epub 2019 Au — View Citation

Caporale A, Lee H, Lei H, Rao H, Langham MC, Detre JA, Wu PH, Wehrli FW. Cerebral metabolic rate of oxygen during transition from wakefulness to sleep measured with high temporal resolution OxFlow MRI with concurrent EEG. J Cereb Blood Flow Metab. 2021 Ap — View Citation

Chatterjee S, Caporale A, Tao JQ, Guo W, Johncola A, Strasser AA, Leone FT, Langham MC, Wehrli FW. Acute e-cig inhalation impacts vascular health: a study in smoking naive subjects. Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H144-H158. doi: 10.115 — View Citation

Chatterjee S, Tao JQ, Johncola A, Guo W, Caporale A, Langham MC, Wehrli FW. Acute exposure to e-cigarettes causes inflammation and pulmonary endothelial oxidative stress in nonsmoking, healthy young subjects. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 1 — View Citation

Kligerman S, Raptis C, Larsen B, Henry TS, Caporale A, Tazelaar H, Schiebler ML, Wehrli FW, Klein JS, Kanne J. Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions. Radiology. 2020 Mar;294(3):491-505. doi: 10.1148/radiol.2020192585. Epub 2020 Jan 28. — View Citation

Langham MC, Caporale AS, Wehrli FW, Parry S, Schwartz N. Evaluation of Vascular Reactivity of Maternal Vascular Adaptations of Pregnancy With Quantitative MRI: Pilot Study. J Magn Reson Imaging. 2021 Feb;53(2):447-455. doi: 10.1002/jmri.27342. Epub 2020 Aug 25. — View Citation

Wehrli FW, Caporale A, Langham MC, Chatterjee S. New Insights From MRI and Cell Biology Into the Acute Vascular-Metabolic Implications of Electronic Cigarette Vaping. Front Physiol. 2020 May 21;11:492. doi: 10.3389/fphys.2020.00492. eCollection 2020. — View Citation

Zamani P, Proto EA, Wilson N, Fazelinia H, Ding H, Spruce LA, Davila A Jr, Hanff TC, Mazurek JA, Prenner SB, Desjardins B, Margulies KB, Kelly DP, Arany Z, Doulias PT, Elrod JW, Allen ME, McCormack SE, Schur GM, D'Aquilla K, Kumar D, Thakuri D, Prabhakaran K, Langham MC, Poole DC, Seeholzer SH, Reddy R, Ischiropoulos H, Chirinos JA. Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism. ESC Heart Fail. 2021 Aug;8(4):2698-2712. doi: 10.1002/ehf2.13329. Epub 2021 May 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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
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.	PWV calculation occurred at two time points: 1) pre-vaping, 2) Fifteen minutes post-vaping.
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.	Flow mediated dilation calculation occurred at two time points: 1) pre-vaping, 2) 40 minutes post-vaping.
Primary	Change in Washout Time Post-Vaping	Transit time of desaturated capillary blood from tissue to the imaging location after e-cigarette vaping	Washout time calculation occurred at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping
Primary	Change in Upslope Post-Vaping	Tissue oxygen resaturation rate after e-cigarette vaping.	Upslope was calculated at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping
Primary	Change in Overshoot Post-Vaping	Degree of overcompensatory effect post-vaping in the supply of oxygen after ischemia.	Overshoot was calculated at two time points: 1) pre-vaping, and 2) 40 minutes post-vaping.
Primary	Change in Breath Hold Index Post-Vaping	Rate of increase in blood flow velocity in the superior sagittal sinus from intermittent volitional apnea.	Breath hold index was calculated at two time points: 1) pre-vaping, 2) five minutes post-vaping.