The Cardiovascular Effects of Electronic Hookah Vaping

Investigating the Cardiovascular Toxicity of Exposure to Electronic Hookah Smoking

Hookah (water-pipe) tobacco smoking has quickly grown to become a major global tobacco epidemic among youth; with electronic (e-) hookahs more recently increasing in popularity especially among young female adults, who endorse marketing claims that these products are a safer alternative to traditional hookah, but scientific evidence is lacking. The study aims to elucidate the comparative effects of traditional hookah smoking vs. e-hookah vaping on human vascular and endothelial function; and examine the role of inflammation and oxidative stress, as likely mechanisms in hookah-related cardiovascular disease pathogenesis.

Study Overview

• Status: Completed
• Conditions: Inflammation; Endothelial Dysfunction; Oxidative Stress
• Intervention / Treatment: Other: Traditional hookah smoking; Other: Electronic hookah vaping

Detailed Description

Hookah (water-pipe) tobacco smoking is rapidly increasing in popularity worldwide. Contributing to this popularity is the unsubstantiated belief that traditional charcoal-heated hookah smoke is detoxified as it passes through the water-filled basin. More recently, electronic (e-) hookahs-containing flavored e-liquid that is heated electrically but inhaled through traditional water-pipes-are increasing in popularity in the United States among young female adults, who endorse marketing claims that these products are even safer than traditional charcoal-heated hookah products. The objective of this project is to investigate the comparative effects of traditional charcoal-heated hookah smoking versus e-hookah vaping on endothelial and vascular function and their mechanistic role in the development of cardiovascular disease. The investigators will test the hypothesis that: 1) in the absence of burning charcoal briquettes and virtually any carbon monoxide (CO) exposure, e-hookah vaping acutely impairs endothelial function and evokes acute central arterial stiffness, opposite from the endothelial function augmentation observed after traditional charcoal-heated hookah smoking, which is likely mediated by the large CO boost emitted from burning charcoal briquettes used to heat the flavored hookah tobacco; and 2) the processes of oxidative stress and inflammation play a pivotal mechanistic role underlying these vascular changes. Accordingly, in a cross-over study comparing traditional hookah smoking to e-hookah vaping, the investigators will assess endothelial function measured by brachial artery flow-mediated dilation and aortic stiffness by pulse wave velocity and augmentation index in 18 young healthy hookah smokers 21-39 years old, before and after ad lib 30-minute smoking/ vaping exposure sessions. To test for oxidative stress mediation, the investigators will determine if any acute impairment in endothelial function after e-hookah can be prevented by intravenous Vitamin C infusion, a potent anti-oxidant. Inflammatory and oxidant biomarkers, as well as smoking exposure biomarkers will be collected before and after the exposure sessions. The results of this proposal: (a) stand to fill in gaps in our mechanistic understanding of the comparative effect of traditional vs. e-hookah bowl on vascular and endothelial function; and (b) help inform policy decisions by the FDA about regulation of hookah products.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-8361
      • University of California, Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 21-39 years old hookah smokers: smoked hookah >12x in last 12 months
• no history of illicit drugs or marijuana
• no evidence of cardiopulmonary disease by history/ physical
• no diabetes: fasting blood glucose <100 mg/dl
• BP<140/90mmHg
• resting HR<100 bpm
• BMI<30kg•m2
• no prescription medication

Exclusion Criteria:

• exhaled CO>10 ppm (smoking non-abstinence)
• positive pregnancy test
• psychiatric illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Traditional Charcoal-Heated Hookah followed by Electronic Hookah; Participants were invited to smoke a 30-minute traditional charcoal-heated hookah-smoking session, followed by a 30-minute electronic hookah vaping session. To mitigate the impact of carryover effects, the two sessions were separated by a minimum of 7-days.	Other: Traditional hookah smoking; Charcoal-heated hookah smoking; Other Names: Combustible hookah smoking; Other: Electronic hookah vaping; Electronic hookah bowl inhalation
Experimental: Electronic followed by Traditional Charcoal-Heated Hookah; Participants were invited to vape a 30-minute electronic hookah session, followed by a 30-minute traditional charcoal-heated hookah smoking session. To mitigate the impact of carryover effects, the two sessions were separated by a minimum of 7-days.	Other: Traditional hookah smoking; Charcoal-heated hookah smoking; Other Names: Combustible hookah smoking; Other: Electronic hookah vaping; Electronic hookah bowl inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-Mediated Dilation (FMD)	Using ultrasound, FMD of the brachial artery induced by reactive hyperemia, was used to measure endothelium-dependent vasodilator function. Baseline diameter and velocity were recorded for 45 seconds and resumed 30 seconds before cuff deflation and continuously for 2 minutes after deflation to obtain true peak vasodilatory response.	Pre- and post- the 30-minute smoking or vaping exposure sessions
Carotid-Femoral Pulse Wave Velocity (Cf-PWV)	Using applanation tonometry, cf-PWV was used to measure central arterial stiffness.	Pre- and post- the 30-minute smoking or vaping exposure sessions
HDL Oxidant Index (HOI)	Capacity was determined as the ability of HDL to inhibit LDL-induced oxidation of dihydrodichlorofluorescein into the fluorescent dichlorofluorescein. Capacity was expressed as an HDL oxidative index, determined by the ratio of dichlorofluorescein fluorescence in the presence and absence of HDL. An index of < 1.0 denotes protective antioxidant HDL, whereas an index of > 1.0 indicates pro-oxidant HDL.	Pre- and post- the 30-minute smoking or vaping exposure sessions
Paraoxonase-1 (PON-1) Activity	PON-1 activity was determined by the ability of PON-1, associated with HDL, to hydrolyze paraoxon substrate. The hydrolysis of paraoxon (diethyl-p-nitrophenyl phosphate) to p-nitrophenol by PON-1 was determined by incubating 5 mL of plasma with 1.0 mM paraoxon in 100 mM tris-HCl buffer (pH, 8.5). Unit of Measure: expressed as micromoles of p-nitrophenol formed per minute for every 1 mL plasma.	Pre- and post- the 30-minute smoking or vaping exposure sessions
Arylesterase Activity	Arylesterase activity (lipid peroxidation biomarker) was determined by the rate of hydrolysis of phenyl acetate to phenol. Briefly, 4 mL plasma was incubated with 3.5 mM phenyl acetate in 9 mM Tris-HCl buffer (pH, 8.0) containing 0.9 mM CaCl2 at RT. The kinetics of phenol formation were determined by recording the absorbance at 270 nm every 15 s for 2 min. Unit of Measure: nanomoles of product formed per minute per milliliter of plasma.	Pre- and post- the 30-minute smoking or vaping exposure sessions.
High-sensitivity C-reactive Protein (Hs-CRP) Levels	Plasma hs-CRP (inflammatory biomarker)	Pre- and post- the 30-minute smoking or vaping exposure sessions
Tumor Necrosis Factor-α (TNFα) Concentrations	Plasma TNFα (inflammatory biomarker)	Pre- and post- the 30-minute smoking or vaping exposure sessions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-Mediated Dilation (FMD)	Using ultrasound, FMD of the brachial artery, induced by reactive hyperemia, was used to measure endothelium-dependent vasodilator function after intravenous infusion of antioxidant ascorbic acid. Infusion of antioxidant ascorbic acid was done before the e-hookah vaping session.	Effect of FMD with e-hookah vaping examined after pretreatment of intravenous infusion of antioxidant ascorbic acid (administered over 60 minutes at 0.5 mL min-1)
Endothelium-independent Vasodilator Function (Control Test for Endothelium-dependent Vasodilator Function)	As a control test for the assessment of endothelium-dependent vasodilator function, using ultrasound the brachial artery, endothelium-independent dilatation was assessed by administering sublingual nitroglycerin. This measure was assessed 10 minutes after FMD testing. Ultrasound images were recorded continuously for a total of 10 minutes	Pre- and post- sublingual administration of nitroglycerin (0.15 mg), which was administrated before and after e-hookah vaping.
Augmentation Index (AI)	AI was used to measure central stiffness. It was calculated as the ratio of augmentation pressure (difference between the second and first systolic peaks of the aortic pressure waveform) and pulse pressure expressed as a percentage.	Pre- and post- the 30-minute smoking or vaping exposure sessions
Interleukin 6 (IL-6) Levels	Plasma IL-6 (inflammatory biomarker).	A change between two points is reported below (e.g., value at post-exposure session minus value at pre-exposure session).
Interleukin 10 (IL-10) Levels	Serum IL-10 (anti-inflammatory biomarker)	A change between two points is reported below (e.g., value at post-exposure session minus value at pre-exposure session).
Nicotine Levels	Plasma nicotine levels (smoking or vaping exposure biomarker)	Pre- and post- the 30-minute smoking or vaping exposure sessions
Carbon Monoxide (CO) Levels	Exhaled CO levels (smoking or vaping exposure biomarker)	Pre- and post- the 30-minute smoking or vaping exposure sessions

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)

Publications and helpful links

General Publications

• Rezk-Hanna M, Gupta R, Nettle CO, Dobrin D, Cheng CW, Means A, Brecht ML, Tashkin DP, Araujo JA. Differential Effects of Electronic Hookah Vaping and Traditional Combustible Hookah Smoking on Oxidation, Inflammation, and Arterial Stiffness. Chest. 2022 Jan;161(1):208-218. doi: 10.1016/j.chest.2021.07.027. Epub 2021 Jul 21.
• Rezk-Hanna M, Seals DR, Rossman MJ, Gupta R, Nettle CO, Means A, Dobrin D, Cheng CW, Brecht ML, Mosenifar Z, Araujo JA, Benowitz NL. Ascorbic Acid Prevents Vascular Endothelial Dysfunction Induced by Electronic Hookah (Waterpipe) Vaping. J Am Heart Assoc. 2021 Feb;10(5):e019271. doi: 10.1161/JAHA.120.019271. Epub 2021 Feb 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2018
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): September 27, 2021

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 1R21HL145002-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No