5 November 2019

Smoking-related diseases: what are atherosclerosis and emphysema?

Quitting smoking altogether is the best way for an adult smoker to minimize his or her risk of developing smoking-related diseases like atherosclerosis and emphysema. Atherosclerosis is the build-up of fats and cholesterol in the walls of arteries and is the major cause of cardiovascular disease (CVD). It can lead to high blood pressure and blood clots, and even heart attack and stroke. Emphysema, a form of chronic obstructive pulmonary disease (COPD), is a lung condition that causes breathing difficulty. It is caused by damage to the alveoli – small air sacs – in the lungs.  As emphysema doesn’t improve with medical treatment, the best that can be done is to halt its progress.

Despite knowing these dangers, some people do not quit tobacco and nicotine products altogether. In this case, switching to a heated tobacco product such as Platform 1 or Platform 2 may be a better choice than continuing to smoke cigarettes. The goal of this study was to investigate the impact of cigarette smoke and the aerosols of our two heated tobacco products on the cardiovascular and respiratory systems of ApoE-/- mice.

 

 
Screenshot of publication online

This article was published in the journal Food and Chemical Toxicology, and you can read the toxicology inhalation/cessation study for more details.

 

Why study ApoE-/- mice?

The ApoE-/- mouse is genetically susceptible to spontaneous development of diseases like emphysema and atherosclerosis, giving these mice an important role in comparing the effects of cigarettes and smoke-free products on the development of these diseases. Cigarette smoke is known to worsen the symptoms significantly in these mice. Although these conditions develop a little differently in mice compared to humans, the development is similar enough that important insights can be gained. You can also learn more about the ApoE-/- mouse model from another of our publications.

Single product use, switching, or cessation in mice

In this study, all procedures involving the mice were performed in an accredited and licensed1 facility with approval from an Institutional Animal Care and Use Committee. The mice were exposed to cigarette smoke or aerosol from either Platform 1 or Platform 2 at a level of 28 micrograms of nicotine per liter of air. They were whole-body exposed to the smoke or aerosol for three one-hour exposures, five days a week, for up to six months. Another group of mice were not exposed to any aerosols, only to fresh air. We call this the “sham-exposed” group, which provides a negative control, showing what changes happen in the mice that are not exposed to a smoke or an aerosol.

A separate group of mice were exposed to cigarette smoke for the first three months, followed by either cessation or switching to Platform 2 aerosol for the final three months of the study. These last two scenarios are particularly important because the results of this group relates to smokers who quit smoking and those who switch to Platform 2.

Mice toxicology study methodology diagram

Design of the Study. Mice were exposed to fresh air (sham), cigarette smoke, or aerosols from Platform 1 or Platform 2 for six months. The cessation and switching group were exposed for three months to cigarette smoke, followed by three months of either fresh air (cessation) or Platform 2 aerosol. The exposure table on the right shows the exposure schedule for all mice in the study, repeated 5 days a week.
Adapted from Phillips et al

 
 

Results: the effect of cigarettes vs heated tobacco on the cardiovascular and respiratory system

Overall, this study clearly demonstrated that the aerosols of our heated tobacco products have less of an impact on the cardiovascular and respiratory systems of ApoE-/- mice than cigarette smoking, and are not significantly different from the effects of smoking abstinence. The study also concluded that the results of switching to Platform 2 aerosol and cessation were similar between the two groups of mice.

All groups of mice experienced some progression of atherosclerosis during the six-months study, but those exposed to cigarette smoke showed the strongest advancement. The mice exposed to cigarette smoke had larger areas of atherosclerotic plaques than the other groups. Those exposed to heated tobacco aerosol had similar sized plaque areas as the sham group.  The cessation group and the group that switched to Platform 2 also had similar plaque areas to each other. In these groups, the plaque areas were larger than those of the sham-exposed group but smaller than those of the mice exposed to cigarette smoke for the duration of the study. 

 
P1 and P2 aerosol effects on aorta vs smoking

 

 

Exposure to heated tobacco aerosols caused less lung inflammation, lower emphysema scores, smaller (i.e., better) lung volume, and better lung function after six months compared to cigarette smoke exposure. These changes are all related to damage to the alveoli, which are tiny air sacs in the lungs. When they are badly damaged by smoke, their walls collapse, forming larger sacs. This increases the overall lung volume, making it hard for a person to fully exhale, and thus raising the emphysema score. All these results of the groups exposed to heated tobacco aerosols more closely resembled the results of the sham-exposed group than those of the smoke-exposed group. The switching and cessation groups showed stabilization of the lung function-related measures, and some improvement in inflammation measurements.

 
P1 and P2 aerosol effects on lungs vs smoking
 

There were many more health effects that were analyzed as part of this study, giving us even more insights into the likely differences between exposure to cigarettes and to our heated tobacco products. Together, the primary analysis and the molecular analyses highlight a reduced impact of these heated tobacco products on the cardiovascular and respiratory systems of these mice compared with continued smoking.

To learn more about this toxicology inhalation/cessation study, you can check out the peer-reviewed publication, or view the presentation given by Dr. Justyna Szostak at several conferences, including the 54th Congress of the European Societies of Toxicology: EUROTOX 2018, organized by the Belgian Society of Toxicology and Ecotoxicology (BelTox). This study has also been neatly explained on INTERVALS.science.

 

1 The facility was accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International, and was licensed by the Agri-Food & Veterinary Authority of Singapore.

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