INTRODUCTION
Electronic cigarette (e-cigarette) use, or vaping, in the worldwide is increasing. Less than a decade ago, the e-cigarette was an obscure product marketed as a safe, tobacco-free alternative to conventional cigarettes by a single company in China. Seven years ago, the electronic nicotine delivery device entered the US market. Today, health officials, policy makers, and researchers are all scrambling to keep up with a rapidly expanding, wildly controversial, and largely unregulated $3 billion global industry that has, at last count, 466 brands, 7,764 flavors (bubblegum, cherry crush, bacon, java jolt, menthol), and slick, youth-oriented Big Tobacco marketing designed to create the perception that e-cigarettes are not only safe, but cool.
Non-nicotine, but an abundant amount of toxic chemicals produced by the combustion of tobacco are the cause of well-known health problems. E-cigarette vapor contains no or only minimal quantities of potentially harmful substances. Hence it can be assumed that vaping in adults is much less harmful than smoking of cigarettes. Furthermore, no data exist that e-cigarettes will encourage youngsters to become cigarette smokers. E-cigarette vaping has the potential to reduce the daily number of cigarettes smoked or facilitates cessation of smoking in heavily nicotine-dependent smokers, who keep on smoking despite a structured smoking cessation program. Health professionals should be aware of this type of nicotine substitution, since the controversial discussion is often emotional and not evidence-based.
The Food and Drug Administration (FDA) rejected these claims, and in September of 2010 they informed the President of the Electronic Cigarette Association that warning letters had been issued to five distributors of e-cigarettes for “violations of good manufacturing practices, making unsubstantiated drug claims, and using the devices as delivery mechanisms for active pharmaceutical ingredients.”
People use is highly controversial from scientific, political, financial, psychological, and sociological ideologies. Given the controversial nature of e-cigarettes and vaping, how should medical care providers advise their patients? To effectively face this new challenge, health care professionals need to become more familiar with the existing literature concerning e-cigarettes and vaping, especially the scientific literature. Thus, the aim of this article is to present a review of the scientific evidence-based primary literature concerning electronic cigarettes and vaping.

THE RESEARCH OF VAPING: Nicotine Content, Delivery, and Pharmacokinetics, Consumer-Based Surveys, Chemical Analysis of E-Cigarette Cartridges, Solutions, and Mist, & Clinical and Physiological Effects of Acute Vaping.
One study had shown that E-cigarettes are designed to deliver nicotine in an aerosolized manner that simulates an authentic smoking experience without the real smoke. In this respect, e-cigarettes are similar to the FDA-approved nicotine inhaler. Bullen C, McRobbie H, determined the Ruyan e-cigarette had a nicotine pharmacokinetic profile very similar to the Nicotrol inhaler, but the study’s participants thought the e-cigarettes were more pleasant to use and produced less irritation to the mouth and throat. For e-cigarettes, the nicotine is delivered through cartridges prefilled with a nicotine solution or cartridges that the user fills with a nicotine refill solution. In either case, the nicotine concentration of the solutions or cartridges can be purchased in strengths ranging from 0 to 24 mg or more, according to user preference. Unfortunately, the amounts of nicotine specified on the labels of various brands of e-cartridges and solutions have not always been accurate or consistent, said by Cheah NP, Chong NW. The FDA confirmed the ability of e-cigarettes to deliver nicotine, but stated there is too much variability in the amount of nicotine delivered per puff of any e-cigarette cartridge for them to be considered safe. The FDA also detected small quantities of cotinine, a metabolite of nicotine, and several nicotine related impurities to include, anabasine, anatabine, myosmine, but not all, e-cartridge solutions and mist samples analyzed. The research shown that awareness of e-cigarettes has quadrupled between 2009 and 2011 and that they have a high adoption rate among traditional smokers. Many current and ex-smokers use e-cigarettes as a nicotine replacement therapy (NRT) to help them reduce or quit smoking while others use e-cigarettes as a less harmful alternative to smoking, state by Etter JF. At the end of 6 months, Polosa et al. found that vaping e-cigarettes decreased consumption of conventional cigarettes by 80% after 6 months and 50% after 24 months. Caponnetto P reported similar reductions in cigarette consumption and cigarette abstinence after a year-long trial of using e-cigarettes in both normal smokers and in chronic schizophrenic smokers. The authors claim that withdrawal symptoms were minimal and that the perception and acceptance of e-cigarettes was satisfactory, even in the schizophrenic patients.
The results of Vickerman KA are less optimistic. They reported that nearly a third of 2758 callers to six state tobacco quit lines had ever used e-cigarettes of which 61.7% used the e-cigarettes for <1 month. Barbeau reported AM that using e-cigarettes, in comparison to other FDA-approved NRTs, such as nicotine gum, patches, and inhalers, had less annoying side effects and were more effective in preventing relapse, primarily because vaping retained the psychosocial aspects of real smoking better than the FDA-approved NRTs. Hua M, found a total of 405 different health-related effects (78 positive, 326 negative, and 1 neutral) reported by e-cigarette users in three different online forums. Users reporting negative health-related effects often reported multiple symptoms, while users reporting positive health-related effects usually reported a single symptom. Additionally, negative health-related effects occurred most frequently in the respiratory, neurological, sensory, and digestive systems while the positive health-related effects occurred solely in the respiratory system. The ingredients found in e-cigarette cartridges and solutions are relatively few, and for the most part non-toxic and non-carcinogenic, especially in the low quantities delivered. They include nicotine, propylene glycol, glycerin, and tobacco flavoring. Propylene glycol, an FDA-approved solvent used in foods, a vehicle for intravenous diazepam, and as the major ingredient found in e-cigarette fluids, makes up about 90% of the solution. Certain contaminates, most of which are derived from tobacco flavoring, have been detected in e-cigarettes. A small amount of diethylene glycol, a known carcinogen and an ingredient in anti-freeze, was also detected in one out of 18 cartridges analyzed by the FDA. While investigations have shown some of these hazardous compounds to be present in e-cigarette cartridges, solutions, and mist, there are only a few reports detecting levels of these contaminates high enough to be of significant risk to humans. The HNZ study found levels of arsenic cadmium, chromium, nickel, and lead to be undetectable in e-cigarette cartridge liquid. In contrast, Williams.M found levels of lead, chromium, and nickel in e-cigarette aerosol to be equivalent to, and in some cases higher than, what has been reported for cigarette smoke. They indicate that the primary source of these trace metals are the filaments inside the e-cigarette cartomizer and conclude that improved quality control of e-cigarette design and manufacturing would greatly reduce the presence of these trace metals. Across BU’s Medical Campus from Spira, Michael Siegel, a physician and professor of community health sciences at the School of Public Health, has emerged as perhaps the country’s most high-profile public health advocate for e-cigarettes. Siegel, who is not currently researching e-cigarettes, says he believes that the device could potentially help large numbers of smokers quit, or drastically decrease, a habit that is the leading cause of preventable deaths in the US. He points out that despite all the existing smoking cessation products on the market, only a small fraction of cigarette smokers manage to quit. Only 4 to 7 percent break the habit without some nicotine replacement or medication, according to the American Cancer Society. At the same time, Siegel says, more research is needed on the health effects of e-cigarettes as well as their effectiveness in helping people quit smoking. The study also make on clinical and physiological effects of acute vaping. The harmful effects of smoking on human health are obvious and well documented. In contrast, effects of vaping on human health are inconclusive due to the extreme paucity of empirical research investigating the presence of vaping-induced health hazards and/or benefits. Few studies have actually reported deleterious effects of vaping. In one report, McCauley et al. present a case study concerning a 42-year-old woman diagnosed with exogenous lipoid pneumonia due to e-cigarette use. She presented with a 7-month history of dyspnea, productive cough, and fevers which coincided with her use of e-cigarettes. Samples of her sputum, and bronchoalveolar lavage revealed lipid-laden macrophages. Glycerin, an ingredient added to e-cigarette solutions for the purpose of producing visual smoke when vaping, was thought to be the causative agent. Computed axial tomography (CAT) images of her lungs revealed areas of patchy ground glass superimposed on interlobular septal thickening, a pattern typical of a restrictive ventilatory defect with diffusion impairment, and consistent with the patient’s diagnosis. Cessation of e-cigarette use resulted in improvement of her symptoms that was verified by follow-up lung radiography, however, pulmonary function testing still indicated mild diffusion impairment. Since the case study does not reveal if the patient is a current or ex-smoker and for how long, it is unclear whether the persistent diffusion impairment is a result of a concurrent or previous smoking habit, the use of e-cigarettes, or the after effects of lipoid pneumonia per se. Romagna.G, who demonstrated that an extract of e-cigarette mist was less cytotoxic to cultured murine fibroblasts than an extract of tobacco cigarette smoke. A further indication that there are differences in the inflammatory responses between vapers and smokers is illustrated in a study reporting an absence of increased inflammatory indices in smokers asked to vape for 30 min compared to smokers who were asked to smoke for 30 min. Acute smoking has long been known to increase white blood cell count, which is a sign of acute inflammatory load. Flouris.AD were able to confirm elevations of white blood cell count, lymphocyte count, and granulocyte count in active smokers but not in active vapers. Support for this is seen in a recently published case report where a 36-year-old male with a nine pack-year history of smoking exhibited reversal of chronic idiopathic neutrophilia symptoms after he quit smoking and started vaping.
CONCLUSION
Despite the popularity e-cigarettes have gained worldwide, very little rigorous research has been done regarding the effects these devices have on human health. This article reviews the existing evidence-based literature, dealing with surveys soliciting personal views on vaping; studies analyzing potential toxins and contaminants in e-cigarette cartridges, solutions, and mist; reports profiling nicotine content, delivery, and pharmacokinetics; and clinical and physiological studies investigating the effects of acute vaping. When compared to the harmful effects of smoking, these studies suggest that vaping could be used as a possible “harm reduction” tool. There is evidence supporting e-cigarettes as an aide for smoking cessation, at least as successful as currently available FDA-approved NRTs. Less evidence exists to suggest that e-cigarettes are effective in recovery from nicotine dependence. More rigorous research is essential before any solid conclusions can be drawn about the dangers, or usefulness of e-cigarettes. In particular, more rigorous research is required delving into both acute and long-term cardiopulmonary effects of vaping, especially those experiments comparing the effects of vaping with those of smoking. E-cigarettes are fast becoming a new “tobacco” industry that could reduce the incidence of traditional smoking. It is also possible that e-cigarettes may either decrease or increase the incidence of nicotine addiction. Given these uncertainties, will the availability of e-cigarettes provide for healthier U.S. and world populations, as harm reductionists hope, or will other more dangerous ill effects ultimately emerge? Health care professionals must remain current with the literature concerning e-cigarettes and vaping. Only then can they make informed decisions aimed at maximizing human safety and minimizing the potential ill effects e-cigarettes may have on their patients and the public. Only then can the new challenge regarding e-cigarettes and vaping in clinical medicine and public health be adequately addressed.

REFERENCES: 1. Regan AK, Promoff G, Dube SR, Arrazola R. Electronic nicotine delivery systems: adult use and awareness of the ‘e-cigarette’ in the USA. http://tobaccocontrol.bmj.com/content/22/1/19 2. Etter JF. Electronic cigarettes: a survey of users. BMC Public Health (2010) http://www.biomedcentral.com/1471-2458/10/231 3. Polosa R, Caponnetto P, Morjaria JB, Papale G, Campagna D, Russo C. Effect of an electronic nicotine delivery device (e-cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health (2011) http://www.biomedcentral.com/1471-2458/11/786 4. Polosa R, Morjaria JB, Caponnetto P, Campagna D, Russo C, Alamo A, et al. Effectiveness and tolerability of electronic cigarette in real-life: a 24-month prospective observational study. http://link.springer.com/article/10.1007%2Fs11739-013-0977-z 5. Caponnetto P, Campagna D, Cibella F, Morjaria JB, Caruso M, Russo C, et al. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One (2013) http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066317 6. Barbeau AM, Burda J, Siegel M. Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach. Addict Sci Clin Pract (2013) http://www.ascpjournal.org/content/8/1/5 7. Romagna G, Allifranchini E, Bocchietto E, Todeschi S, Esposito M, Farsalinos KE. Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract. Inhal Toxicol (2013) http://www.tandfonline.com/doi/abs/10.3109/08958378.2013.793439?journalCode=iiht20 8. Flouris AD, Poulianiti KP, Chorti AZ, Jamurtas MS, Kouretas D, Owolabi EO, et al. Acute effects of electronic and tobacco cigarette smoking on complete blood count. Food Chem Toxicol http://www.sciencedirect.com/science/article/pii/S0278691512005030 9. Bridges AB, Hill A, Belch JJ. Cigarette smoking increases white blood cell aggregation in whole blood. J R Soc Med (1993) 10. Moorea TW, Allgirea JF, Woodruffa JT, Ahadia SS, Blacka JC, Westenberger BJ. Analysis of electronic cigarette Cartridges, refill solutions and smoke from nicotine and nicotine related impurities. J Liq Chromatogr Relat Technol 11. Williams M, Talbot P. Variability among electronic cigarettes in the pressure drop, airflow rate, and aerosol production. Nicotine Tob Res (2011) http://ntr.oxfordjournals.org/content/13/12/1276 12. Hua M, Yip H, Talbot P. Mining data on usage of electronic nicotine delivery systems (ENDS) from YouTube videos. J Med Internet Res (2013) http://tobaccocontrol.bmj.com/content/22/2/103 13. Sherwood N. Effects of nicotine on human pschomotor performance. Hum Psychopharmacol (1993) http://onlinelibrary.wiley.com/doi/10.1002/hup.470080302/abstract 14. Dawkins L, Turner J, Hasna S, Soar K. The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition. Addict Behav (2012) http://www.ncbi.nlm.nih.gov/pubmed/22503574 15. Evans DE, Drobes DJ. Nicotine self-medication of cognitive-attentional processing. Addict Bio (2009) http://www.ncbi.nlm.nih.gov/pubmed/18855804