In the past 50 years, 31 surgeon general reports have cited the strongest scientific evidence linking tobacco cigarette (TC) smoke exposure with adverse health consequences, and have detailed the known multiple mechanisms underlying cardiovascular toxicity, including increased oxidative stress, increased adrenaline levels, and blood vessel damage. We are facing a new challenge with the soaring popularity of electronic cigarettes (ECs), which deliver aerosolized nicotine, propylene glycol, vegetable glycerin, and flavors, but without combustion. Although not known to cause cancer, aerosolized nicotine inhalation irritates the lungs; acute and chronic inhalation may lead have the same adverse effects identifed for TCs. In fact, in our preliminary studies, we have found increased oxidative stress and adrenaline levels in chronic EC users. We also have preliminary evidence supporting a critical role for the nicotine in the ECs as a cause of these abnormalities; this role will be further illuminated by the proposed studies. The proposed studies exploring EC effects on the known pathways by which TCs lead to cardiovascular toxicity will provide much needed scientific data regarding the relative toxicities of ECs, providing a sound basis for their regulation.
Our overall objective is to determine the cardiovascular toxicity associated with acute and chronic EC use. Our overarching hypothesis is that EC aerosol exposure initiates oxidative stress and inflammation leading to increased adrenaline levels and abnormal blood vessel function that 1) is driven by inhalation of aerosolized nicotine, an airway irritant, and 2) is intermediate between TC smokers and non-smoking volunteers.
Our approach in these studies will be twofold. First, we will determine the relative effects of chronic EC use vs chronic TC use on oxidative stress and inflammation, and its effects on adrenaline levels and abnormal blood vessel function. We will test the hypothesis that chronic EC exposure in humans leads to augmented airway and systemic oxidative stress in EC users, leading to effects on adrenaline levels and blood vessel function that are intermediate between TC smokers and nonsmoking volunteers.
Secondly, we will assess to what extent acute exposure to EC emissions, in non-smoking individuals, leads to acute oxidative stress and inflammation, and its sequelae. We will test the hypothesis that, similar to brief TC exposure, brief exposure to EC aerosol will induce acute increases in oxidative stress and inflammation, accompanied by increased adrenaline levels and abnormal blood vessel function.
In summary, through years of scientific research, the many mechanisms by which TCs cause cardiovascular toxicity have been identified, including oxidative stress, blood vessel damage and increased adrenaline levels. These scientific data have contributed to strict anti-smoking policies, and the "de-normalization" of smoking. Now the widespread appeal of ECs, especially to our youth, threatens the progress of the anti-smoking campaigns that have successfully decreased societal nicotine addiction. Although it is generally conceded, yet unproven, that ECs may be safer than TCs, it is highly unlikely that they are harmless. Thus, the role of ECs in activating of the same pathways activated by TCs, as outlined in this proposal, has the potential for high impact on the development of sound policies regulating ECs.