EVALUATION OF ACUTE AND SUBACUTE EFFECTS OF NICOTINE FREE ELECTRONIC CIGARETTE (NFEC) VAPORS -Aim 2.1 of "Adverse Effects of Inhaled Nicotine From Tobacco and E-cigarettes".

The recent introduction of electronic cigarettes (ECs) to provide habitual smokers a source of nicotine without the need to inhale tobacco smoke is thought to reduce toxicity to airway epithelial cells. The use of ECs decreases use of traditional cigarettes diminishes nicotine withdrawal symptoms leads to opposite effects on exhaled NO levels compared to tobacco and may diminish stimulation of reward centers in the brain leading to less dependence due to the lack of other tobacco-derived chemicals. The manufacturers of ECs tout comparative safety as a reason to switch from traditional tobacco cigarettes to their products. However the dearth of data supporting this claim led the FDA to issue warning letters to these companies. For now, the World Health Organization recommends against EC use until ECs have been properly evaluated. On the other hand, the American Association of Public Health Physicians support the use of ECs as a means of "Harms Reduction" since ECs provide nicotine without the myriad of other toxic chemicals produced from burning tobacco. These recommendations are mostly due to theoretical considerations and expert opinion. Due to the novelty of the ECs, many concerns of their safety on health and long-term nicotine addiction remain unanswered due to a lack of studies that comprehensively evaluate their toxicity in the airways.

Moreover, ECs produce vapor mainly from propylene glycol (PG) or vegetable glycerin (VG) that are blended at different concentrations, making comprehensive testing more difficult.

The lack of consistent results demands a full evaluation of EC toxicity in the airway even when nicotine is not inhaled.

In our laboratory using cultures of primary normal human bronchial epithelial(NHBE) cells (either differentiating or fully differentiated) exposed to EC vapor or an equivalent volume of filtered air we have demonstrated that EC vapor can be delivered to fully differentiated NHBE cells and that high, but realistic puff numbers decrease ciliary beat frequency (CBF) as well as Large, Ca2+-activated K+ channels (BK channel) (the pore forming α subunit KCNMA1) and Forkhead box protein (FOXJ)-1 expression. We also have preliminary data of smoke exposure in vitro and in vivo, showing a negative effect of cigarette smoke and nicotine on parameters of mucociliary clearance (MCC) and nasal potential difference (NPD), a way to assess ion transport in vivo. These changes occurred in a TGF-β-dependent manner.

This study is designed to evaluate the airway toxicity of NFECs (Aim 2.1 of the project "Adverse effects of inhaled nicotine from tobacco and e-cigarettes").