Abstract:

Every one in five deaths in the US is due to cigarettes. To combat the detrimental impacts and the widespread use of traditional tobacco cigarettes (TTC), the new e-cigarette (EC) was introduced into the market. It was advertised as a safe and healthy alternative to the TTC. However, there was limited research to provide insight into the long-term impacts of the EC. Our research suggests, however, that ECs are just as bad, if not worse than TTCs. We found that ECs not only lead to lung inflammation, but it also creates an imbalance in pulmonary gas exchange. They also induce airway epithelial injury, while being consumed. In 2020, ECs claimed the lives of almost 2,807 individuals who either faced death or were hospitalized with complications. As the market indulged in the new EC technology, companies like Juul, came out with new flavors of ECs, resulting in a new wave of indulgence by the adolescent population. It has been found that smoking any nicotine product has a negative impact on the developing brain. However, some researchers have found specifically women reduce the risk of cardiovascular disease when they switch from TTCs to ECs. In actuality, these are simply short-term impacts.

Notes:

Introduction:

In the United States, smoking is the leading cause of death. It results in chronic obstructive pulmonary disease, cancers, heart and kidney failure, and other illnesses that rob the smoke of quality life. A drastic increase in smokers has led to a variety of therapies to help quit smoking. Some therapies include pharmacotherapy, which includes nicotine patches, inhalers, gum, and pill drugs. However, it has not always been successful. As the number of smokers increased, manufacturers found new methods to combat the death rates of cigarette smokers in the US. Electronic cigarettes were introduced into the market in 2006. These electronic cigarettes (EC) have an E-liquid formula that can give the same satisfying effects that cigarettes would give. They are being presented as a healthy and safer alternative than tobacco cigarettes (TTC). However, research has found that electric cigarettes present much worse side effects and health impacts than cigarettes. 

There are many different types of ECs in the market today. There is the Juul, the tank device, the rechargeable cigarette, the e-cigar, the e-pipe, and more. The purpose of these devices is to avoid breathing in the smoke produced by regular disposable cigarettes. These ECs create an aerosol using battery power to heat liquid nicotine or other drugs. This may seem better than disposable cigarettes that deposit more than just nicotine in the lungs. Regular cigarettes force carbon monoxide, tar, and radioactive material which results in cancers, and other serious illnesses. However, ECs have a dark side to them as well. ECs are fairly new in the market, making their long-term side-effects unknown. But, their short-term impacts can be evaluated and compared to cigarettes to determine their effectiveness. 

Method Section:

In this section, we present the procedures used to conduct the research that is further analyzed in this study. The procedures are portrayed in a concise manner to illustrate the bigger picture of the procedures at hand.

Role of e-Cigarettes and Pharmacotherapy during Attempts to Quit Cigarette Smoking: The Path Study 2013-16.

This study analyzes the difference of impact using both ECs and pharmacotherapy to quit smoking. It takes a closer look at the data of the Population Assessment of Tobacco and Health (PATH) Studies. The PATH Study was one of the largest collaborations between the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), and Center of Tobacco Products (CTP), Food and Drug Administration (FDA). Almost 150,000 participants, including adults and youth, were sent a survey in the mail asking questions regarding their experiences with smoking, their journey to quit smoking, and their effectiveness. It consisted of three waves of responses from participants, with time gaps. The first wave began in 2013-2014, the second in 2014-2015, and the last in 2015-2016. The first wave of participants was the first point of contact for the study. Participants were asked questions about their smoking habits: how many times a day did they smoke, whether they were trying to quit, what methods were they using to quit smoking, and why were they trying to quit smoking. In the survey for the first wave, there was a section called Last Quit Attempt (LQA). In this section, they asked similar questions, but the questions were more closely aligned with the nature of the method of quitting. Participants were asked if they used ENDS (Electronic Nicotine Delivery System), or they used FDA-approved Pharmaceutical Aid, such as nicotine patches, gum, inhalers, nasal spray, lozenge, or pills. Then in the second wave, the participants that were a part of the first wave were asked how many months, days, or years they experienced abstinence from smoking from the initial wave. Some were asked to submit physical samples of urine, blood, and buccal (cheek) cells. In the third wave, participants that were surveyed were also asked to recall their last attempt to quit smoking.

In this study, the researchers use data from these waves of responses to test their hypotheses. The first hypothesis they analyzed was that participants that used ENDS achieved greater abstinence from smoking compared to their control counterparts. The second hypothesis they tested was that participants that used ENDS achieved equivalent abstinence from smoking compared to participants that used non-e-cigarettes. They used the propensity Score Matching (PSM) method to statistically analyze the data.    

Pod-mod vs. conventional e-cigarettes: nicotine chemistry, pH, and health effects:

This study statistically analyzed the differences between the “pod mod”, also known as the Juul EC to other ECs. Shao and Friedman discuss that nicotine in aqueous solution is found in three forms including deprotonated nicotine, monoprotonated nicotine,  and unprotonated nicotine. The researchers on this experiment disregarded deprotonated nicotine because of its insignificance compared to the other two forms. Using an equation that converts the concentration of mono protonated and unprotonated nicotine into pH levels, Shao and Friedman calculated 10.53 pH for Blu E-liquid and 6.05 pH for JUUL. 

After this, researchers brought electric cigarettes from the websites that sell JUUL and Blu. The E-liquid samples from the electric cigarettes are “diluted 1:10 with deionized H₂O”(Shao and Friedman 2). From there, they used the pH meter to measure the pH in the samples. The difference between the calculated and measured pH for the Blu E-liquid is that the measured result is two pH lower than the calculated results. With JUUL both results are closely related. The researchers speculated that the pH of Blu E-liquid “may have been buffered with acids and other acidic components during the manufacturing process”(Shao and Friedman 2).

The final step is to find pH by using the ratio between the protonated and unprotonated nicotine. The equation that was used is called the Henderson-Hasselbalch equation, which is, 11pH=pKa+log([Nic]/[NicH+]). Using this equation the researchers got the values pH = 8.26 for Blu E-liquid and ph = 6.0 for JUUL E-liquid.   

Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchange disturbances: results from two randomized clinical trials: 

This study was conducted to determine the effects of high-wattage electronic cigarette vaping with and without nicotine on lung inflammation, transcutaneous gas tensions, and pulmonary function tests in young and healthy tobacco smokers. Along with monitoring pulmonary effects in young smokers, arterial blood gas tensions were also assessed in heavy smokers suspected of coronary artery disease. There were 25 members enrolled in the study, 18 of them were men, with a mean age of 23, and a median cumulative pack-year smoking history of 0.2. Participants were chosen by those who do not smoke, do not use nicotine replacement therapy, and do not use recreational drugs. 

The 25 participants were broken up randomly into three experimental sessions, sham-vaping, vaping with nicotine, and without nicotine at 60 W. Data was collected after 20 minutes of rest in a supine position in a noiseless and air-conditioned room at 23°C. To prepare for the first study, fourth-generation e-cigarettes, set at 60 W, were filled with e-liquid. One e-liquid lacked nicotine and one e-liquid had nicotine. Each candidate inhaled vaporized aerosol for 4s, held for 4s, and then exhaled. This procedure was repeated after 25 puffs. Those who did sham vaping were strictly monitored. The quantity of e-liquid consumed was found by measuring the vaping device before and after each usage. 

Researchers assessed the health factors of sham-vaping, vaping with nicotine, and without nicotine by obtaining blood samples that were also taken from participants before as well as 30 and 150 minutes after exposure. Urine and serum creatinine were quantified using the Beckman Synchron Delta Clinical System. Pulmonary function tests were done to check any effects on the lungs, and the MEC PFT body box was used to perform pulmonary function tests. Transcutaneous oxygen and carbon dioxide were also assessed by installing a fixation ring to the skin on the anterior aspect of the right forearm at the level of the heart.

The second study focused on analyzing arterial blood and other cardiorespiratory parameters in heavy smokers. Candidates who had a clear coronary angiogram were to take part. At random, 12 participants were sham-vaping and 12 were vaping without nicotine. Pharmaceutical grade PG and GLY vaping liquid were made and participants had to vape a total of 1g of liquid at 60W. After vaping, participants were placed in quiet rooms to perform their coronary angiogram. Candidates were examined for Po and Pco, pH, oximetry, electrolytes, and metabolites, and arterial samples were drawn.

Results Section:

In a study examining the impact of e-cigarette vaping on inflammation and gas exchange disturbance, Chaumont et al, used three intervention groups. The first group who were exposed to sham vaping, Δ-serum CC16 increased 30 min after vaping without nicotine; however, the serum CC16 reduced to normal levels within150 minutes (Chaumont et al., 2018). The Δ-serum CC16 also increased during vaping with nicotine but decreased back to baseline after 150 minutes post-exposure. Unlike the serum CC16 values, serum PG was found to have a prolonged effect when an individual vaped with nicotine. Serum PG values were higher in participants who vaped with nicotine after 150 minutes post-exposure than participants who did not vape with nicotine. The study established that vaping caused changes in TcpO2 and PO2, which can significantly impact breathing among people with existing respiratory conditions (Chaumont et al., 2018). Acute vaping propylene glycol/glycerol aerosol at high wattage was found to impact the lungs as it resulted in epithelial injuries where nicotine was used or not. 

In a study looking to compare the pHs of JUUL and Blu E-liquids, the study established that the pH levels of e-cigarettes could have possible adverse effects on the smoker. The study calculated the pHs of protonated and unprotonated nicotine and examined their possible effects on the respiratory system. The study found that protonated nicotine concentration in JUUL was seven times higher than in Blu, while unprotonated nicotine was 26 times higher in Blu than in JUUL (Xuesi and Friedman, 2019). While each type of nicotine is high on each kind of e-cigarette, they have different effects on the body. For example, high levels of protonated nicotine can affect cells in charge of inflammation and possibly result in cancer. The study established that JUUL can affect the lungs while Blu can affect the cardiovascular and nervous systems. 

According to Pierce et al., during the research study, the waves of the population were assessed to determine whether any of the interventions was successful. The researchers established individuals often turned to various methods to help with cessation, e-cigarettes, nicotine replacement therapy, or prescription medication. Some participants also reported not using any products to help with cessation. The study established that at W3, there was no difference in smoking whether the method used was e-cigarettes, pharmaceutical aids, or neither product. The researchers also established that the use of e-cigarettes did not significantly impact abstinence compared to the group that did not use e-cigarettes. The results also showed that the abstinence rate in the 12+ month’s abstinence wave was 3 percent lower in the e-cigarette group compared to the no e-cigarette and no product control groups. The study concludes that using e-cigarettes, nicotine replacement therapy, or medication does not increase an individual’s cessation goals in 12+ months or 30+ days. 

 Discussion:

This study investigated the difference in the impact of ECs and traditional cigarettes. It took a closer look at the shortcomings of ECs as a therapy to quit traditional cigarettes. The results from the PATH Study ‘13-’16, demonstrated that both hypotheses were not supported. The hypotheses tested if 1) ENDS achieved greater abstinence from smoking compared to their control counterparts and 2) if participants that used ENDS achieved equivalent abstinence from smoking compared to participants that used non-e-cigarettes. Their results demonstrated that of the total participants enrolled in the study, the portion of those that used ECs in W1 was still using them in a greater dosage in W3. In Shao and Friedman’s research, they found that ECs like Juul and Blu have a much higher dosage of nicotine, equivalent to almost 20 combustible cigarettes. Essentially, those that switch from traditional cigarettes to ECs, end up increasing their nicotine intake drastically, to toxic levels potentially. A research journal published by the International Journal of Environmental Research and Public Health found that smokers that smoked the traditional cigarette experienced reduced craving almost five minutes after smoking (44%), whereas smokers that used vape, or other ECs experienced only a 27% reduction five minutes after smoking. This demonstrates that ECs do not leave one satisfied enough, leaving one craving more; this validates the findings in the PATH ’13-’16 study that ECs may prove more harmful than traditional cigarettes, in the long run.

The randomized trial by the American Heart Association found that ECs were less detrimental than traditional cigarettes. The researchers used blood samples from before the smoking sessions and immediately after the smoking sessions. Their results demonstrated that many of the biological markers that indicate damage were found in fewer concentrations in EC users than traditional cigarette users. One year and one day after, Shao and Friedman analyzed the molecular modules that were processed in EC users. They explained that the higher concentrations of nicotine modulate inflammatory responses, expressing the nAChRs. These nAChRs are expressed in lung cancer cells. With Juul, as the nicotine concentration is elevated, this release of the nAChRs is 7 times more recurrent. In other words, the chance for the development of lung cancer increased drastically, with the intake of Juul. 

Another study by Chaumont, et al. indicated that vaping impacts the lower respiratory tract in disastrous ways. Participants that vaped with nicotine had higher levels of serum PG, compared to participants that vaped without nicotine. Serum PG is known to induce irritation and inflammatory responses in the airways and constrict small airways, in pulmonary evaluations. The main findings of concern are the changes in TcpO2 and PO2 levels that may lead to respiratory illnesses and disturbances with continued use. 

In the end, the findings from various research models and studies suggest ECs are more threatening than traditional cigarettes. However, much long-term research is needed to make a definitive conclusion. As the market for ECs is fairly new, there is no large-scale, long-term research or study to evaluate the severity. However, the research and studies conducted as of yet, hint at a treacherous consequence for the use of ECs to help quit smoking.