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Dual use of cigarettes and vaping devices worse than single use – two US studies

Two related studies show that the combination of smoking and vaping might cause even more damage – a potential red flag for those using e-cigarettes as a cessation.

Traditional tobacco is still believed to be worse for a person’s health than e-cigarettes because of its ties to lung cancer and other breathing issues, but this latest research provides compelling evidence that vapes are not the risk-free alternative as touted by the various manufacturers, reports Daily Mail.

The reports come on the heels of new US federal data saying more than 2.55m middle or high schoolers had used an e-cigarette device within the past 30 days, rising half a million from last year and reversing downward trends in recent years. It is a jump of 500 000, or of 24%, from 2021, and the first increase since the US Centres for Disease Control and Prevention (CDC) started gathering annual data in 2019.

Almost 10% of American adults vape, the organisation says, with federal regulators describing the situation as a “vaping epidemic”.

The researchers received government funding from the National Heart, Lung and Blood Institute, part of the National Institutes of Health.

The findings from experts at the University of California, San Francisco were published in the American Heart Association’s journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB).

Cigarette smoking and e-cigarette vaping are both known to impair endothelial function, which can cause an inability of the large blood vessels to open enough to supply sufficient blood to the heart and other tissues.

Endothelial cells line the blood vessels and maintain blood fluidity, regulate blood flow, and control vessel-wall permeability by generating nitric oxide. Damage to these cells can lead to myriad cardiac and vascular problems such as hypertension and coronary artery disease.

In the pair of studies, one on mice and one on people, e-cigarettes were found to cause similar damage to blood vessels as smoking tobacco.

If blood vessels are damaged or can't function properly, it makes it harder for oxygen-blood to travel to the heart and around the body.

In the mice study, researchers tried to determine if there were specific components of tobacco smoke or e-cigarette vapour that were responsible for blood vessel damage.

They measured arterial flow-mediated dilation (FMD), or the ability of the blood vessels to widen, pre- and post-exposure to smoke from four kinds of traditional combustible cigarettes: conventional nicotine, reduced nicotine, conventional nicotine with added menthol and reduced nicotine with added menthol.

Blood vessel dilation was reduced after use of all four types of cigarettes.

They also exposed the rats to two of the main gases found in both smoke and e-cigarette aerosol, as well as clean carbon nanoparticles to evaluate their effects on blood vessel dilation.

Despite the difference in ingredients that make up e-cigarette aerosol and cigarette smoke, the researchers found that blood vessel damage does not appear to be caused by a specific component of cigarette smoke or e cigarette vapour.

Rather, it appears to be caused by airway irritation, which triggers biological signals in the valgus nerve. It is responsible for the involuntary internal organ functions, that somehow leads to blood vessel damage.

Dr Matthew Springer, a professor of medicine in the division of cardiology at the University of California, San Francisco said: “We were surprised to find that there was not a single component that you could remove to stop the damaging effect of smoke or vapours on the blood vessels.

“As long as there’s an irritant in the airway, blood vessel function may be impaired,” he said.

In the second study, with human subjects, researchers recruited 120 volunteers who included long-term e-cigarette users, long-term cigarette smokers, and non-users.

The scientists collected blood samples from each and exposed those samples to lab-cultured blood vessel cells and measured the release of nitric oxide, which indicates whether the endothelial cells are functioning properly.

The blood from the e-cigarette users and smokers caused a significantly greater decrease in nitric oxide production by the endothelial cells than the blood of non-users.

The also found that blood from the e-cig users caused more permeability in the blood vessel cells than the blood from both tobacco smokers and non-users.

Too much permeability means leaky blood vessels, which can cause a host of inflammatory responses leading to cell damage and heart disease.

They concluded that the blood from tobacco smokers had higher levels of certain circulating biomarkers of cardiovascular risks, and the blood from e-cig users had elevated levels of other circulating biomarkers of cardiovascular risks.

Springer said: “These findings suggest that using the two products together, as many people do, could increase their health risks compared to using them individually… We had not expected to see that.”

The team’s results suggest that regulators such as the US Food and Drug Administration (FDA) cannot rely on prohibiting specific ingredients to avoid the adverse health effects.

“Smoking and vaping can have similar harmful cardiovascular effects but each condition causes some potentially harmful effects that the other does not,” Springer said.

“These differences indicate that dual product use, meaning smoking combustible cigarettes and also using e-cigarette products, may actually be worse for vascular health than either smoking or vaping alone.”

Study details

Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels

Leila Mohammadi, Daniel Han, Fengyun Xu, Abel Huang, Ronak Derakhshandeh, Poonam Rao, Adam Whitlatch, Jing Cheng, Rachel Keith, Naomi Hamburg, Peter Ganz, Judith Hellman, Suzaynn Schick and Matthew Springer.

Published in the journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) on 26 October 2022

Abstract

Background
The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesised that e-cigarette use causes changes in blood milieu that impair endothelial function.

Methods
Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants’ sera, or e-cigarette aerosol condensate, on NO and H2O2 release and cell permeability in cultured endothelial cells (ECs).

Results
E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production.

Conclusions
Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

Study 2 details

Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway

Pooneh Nabavizadeh, Jiangtao Liu, Poonam Rao, Sharina Ibrahim, Daniel Han, Ronak Derakhshandeh, Huiliang Qiu, Xiaoyin Wang, Stanton Glantz, Suzaynn Schick and Matthew Springer.

Published in the journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) on 26 October 2022

Abstract

Background
Exposure to tobacco or marijuana smoke, or e-cigarette aerosols, causes vascular endothelial dysfunction in humans and rats. We aimed to determine what constituent, or class of constituents, of smoke is responsible for endothelial functional impairment.

Methods
We investigated several smoke constituents that we hypothesised to mediate this effect by exposing rats and measuring arterial flow-mediated dilation (FMD) pre- and post-exposure. We measured FMD before and after inhalation of sidestream smoke from research cigarettes containing normal and reduced nicotine level with and without menthol, as well as 2 of the main aldehyde gases found in both smoke and e-cigarette aerosol (acrolein and acetaldehyde), and inert carbon nanoparticles.

Results
FMD was reduced by all 4 kinds of research cigarettes, with extent of reduction ranging from 20% to 46% depending on the cigarette type. While nicotine was not required for the impairment, higher nicotine levels in smoke were associated with a greater percent reduction of FMD (41.1±4.5% reduction versus 19.2±9.5%; P=0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% versus 40.5±4.8%; P=0.048). Inhalation of acrolein or acetaldehyde gases at smoke-relevant concentrations impaired FMD by roughly 50% (P=0.001). However, inhalation of inert carbon nanoparticles at smoke-relevant concentrations with no gas phase also impaired FMD by a comparable amount (P<0.001). Bilateral cervical vagotomy blocked the impairment of FMD by tobacco smoke.

Conclusions
There is no single constituent or class of constituents responsible for acute impairment of endothelial function by smoke; rather, we propose that acute endothelial dysfunction by disparate inhaled products is caused by vagus nerve signalling initiated by airway irritation.

 

ATVB article – Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels (Open access)

 

ATVB article – Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway (Open access)

 

Daily Mail article – Vaping is just as bad as cigarettes for your heart, finds landmark NIH studies — and using both carries biggest risk (Open access)

 

See more from MedicalBrief archives:

 

Major independent evidence review: vaping ‘a small fraction’ of the risk of smoking

 

Adolescent vaping – monitoring needed to detect potential future health issues

 

Survey shows that Australian teenagers have ready access to illegal vaping products

 

E-cigarette Summit: Vaping improves odds of quitting tobacco smoking

 

Researchers expose the ‘pitiful quality’ of highly cited vaping studies

 

 

 

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