A 17-year-old male with no significant past medical history presents to the emergency department after developing severe shortness of breath while at a high school dance. He admits using his friend’s e-cigarette in the school bathroom before developing severe shortness of breath, dizziness, and nausea. He tried to sit and rest without improvement before developing chest pain, which prompted his friends to alert the supervising teacher, who called EMS.

Exam: VS T 38.4 P 150 R 32 BP 135/85. He is anxious, distressed, and sitting on the edge of the hospital bed with his arms on his knees. Respirations are fast, labored, and his lips and fingernails are mildly cyanotic. Despite supplemental oxygen and corticosteroids, the patient’s oxygen saturation drops to 82%, and he is placed on mechanical ventilation and admitted for further management of e-cigarette or vaping product use associated lung injury (EVALI).

EVALI (e-cigarette or vaping product use associated lung injury) was first identified in the summer of 2019, and since then, over 2800 cases of EVALI were reported to the Centers for Disease Control and Prevention (CDC) with approximately 70 resultant deaths. Nearly 80% of all reported EVALI cases involved patients under 35 years old, reflecting a recent trend in tobacco-related disease burden shifting to the youth of the United States (1-3). EVALI is an acute respiratory illness resulting from "vaping", or the process of inhaling an aerosol created by heating solvents such as propylene glycol along with substances such as tetrahydrocannabinol (THC), nicotine, and flavoring additives, that may be severe and life-threatening. EVALI, characterized primarily by acute lung injury resembling organizing pneumonia (OP) and/or diffuse alveolar damage (DAD), is a diagnosis of exclusion with a positive history of vaping within the last 90 days (4). Nicotine and THC products have both been implicated in EVALI, but the multitude of additives and chemicals that carry unknown consequences of long-term inhalation exposure combined with variable patient-specific responses makes it difficult for clinicians to identify reliable signs of vaping-related lung injury. EVALI typically presents with a combination of respiratory, gastrointestinal, and constitutional symptoms. The patient’s course varies widely, but nearly all recorded severe cases required hospitalization and some combination of supplemental oxygen, empiric antibiotics or antivirals for suspected infection, and corticosteroids to combat inflammation. Mechanical ventilation is used in severe cases of EVALI. There is no curative treatment for EVALI, and a widely variable presentation makes studying the disease even more challenging. Evidence of vitamin E acetate present within sampled bronchoalveolar lavage indicates a clear association between acute lung injury and vaping, but the question remains whether vitamin E acetate is causative in the pathophysiology of EVALI or if it simply serves as an exposure marker (5-7). Given the heterogeneity of vaping juices, lenient regulation on contaminants, and patient-specific response to these chemicals, the exact biological effects of e-cigarette use remain poorly understood (1,4,8).

Approximately 36.5 million American adults use tobacco products daily, despite estimates that nearly half of lifetime smokers will die prematurely from their affliction (9). Caregivers or parents may unintentionally expose children to tobacco smoke, and it is well established that tobacco use, second hand smoke (SHS), and third hand smoke (THS) exposure increases the risk of developing cancer, heart disease, stroke, chronic obstructive pulmonary disease (COPD), and many other diseases (10). Tobacco use often leads to nicotine dependence, a chronic, relapsing condition that disproportionately affects vulnerable and disadvantaged groups including ethnic minorities and individuals living in poverty (11-15). Cigarette smoking is the leading cause of preventable morbidity and mortality in the country, affecting every organ system and costing the U.S. healthcare system billions of dollars annually in smoking-related illness (9,16,17). While smoking may be considered a personal choice, it is imperative to recognize the multi-factorial nature of addiction to adequately address the tobacco epidemic. Through a structural competency framework, intervention includes challenging the tobacco industry and their targeted advertising, enforcing prohibition of underage smoking, offering patient education and access to cessation resources (10). Tobacco dependence is discussed within the context of pediatric medicine because extensive research demonstrates that most tobacco use and subsequent addiction begins in adolescence (8,17-20). Recent increases in tobacco use among adolescents revived public health efforts to combat nicotine addiction among America’s youth (6,19). Urgent interventions initiated by legislators at the federal and state level in an attempt to address the threat of nicotine addiction have bolstered anti-smoking campaigning in the U.S.

Table 1: Definitions of terms associated with tobacco use and vaping (2,10)

Tobacco product	Any nicotine delivery product, currently regulated or unregulated by the U.S. Food and Drug Administration (FDA).
Second hand smoke	The smoke emitted from a tobacco product that is inhaled by a nonuser.
Third hand smoke	The smoke absorbed onto surfaces, exposing the nonuser by either direct contact and dermal absorption and/or off-gassing and inhalation.
Electronic nicotine delivery systems (ENDS)	Handheld devices that produce an aerosol from a solution termed e-juice.
e-juice	A solution, typically containing nicotine, flavoring chemicals, and carrier solvents, that is combusted by ENDS producing vapor for inhalation. Alternative names include electronic cigarettes (e-cigarettes), mods, vape pens, and e-hookah.

The Centers for Disease Control and Prevention (CDC) calls on clinicians to remain vigilant in recognizing tobacco use in young adults, especially within the primary care setting. Studies show 90% of adult smokers began their habit before age 19, making adolescence a critical period of vulnerability (5,21,22). Early intervention during adolescence is critical in preventing propagation of the tobacco epidemic. The American Academy of Pediatrics (AAP) policy statement draws a clear association between targeted youth advertising and subsequent e-cigarette initiation among youth (2,10). Risks of cigarette smoking compound over years of use, clinically estimated in terms of pack years, calculated by the number of packs of cigarettes smoked per day multiplied by the number of years the patient has smoked. Extensive research has established a clear correlation between tobacco use and a significantly increased risk of developing numerous life-threatening illnesses (23). Recent studies report an alarming prevalence of e-cigarette use among middle and high school students. According to the 2021 National Youth Tobacco Survey, approximately 4% of middle school students and 13% of high school students reported current use of a tobacco product, with e-cigarettes being the most commonly used product (2,3,9,10,19). While the long-term consequences of inhaling specific chemicals are not fully elucidated, it is well-established that nicotine exposure during adolescence can harm the vulnerable, developing adolescent brain. Chronic exposure to tobacco products leads to dependence and causes destructive physiological changes. Healthcare professionals are urged to follow harm reduction principles and discourage tobacco use in any form. Currently, the USPSTF (U.S. Preventive Services Task Force) concludes there is insufficient research to recommend e-cigarettes for tobacco cessation in adults.

The magnitude of disease burden prompted the first U.S. Surgeon General’s report in 1964, created to identify smoking-related disease burden, outline recommendations to clinicians and lawmakers, and set goals for anti-smoking interventions (9,24). The CDC’s Office on Smoking and Health (OSH) created the National and State Tobacco Control Program (NTCP) in 1999 to coordinate efforts in preventing smoking-related mortality (9). These efforts proved effective as the U.S. experienced a marked decline in conventional cigarette smoking. However, advancements in solving the tobacco epidemic are currently being threatened by the advent of new tobacco products, primarily e-cigarettes, threatening to derail massive progress in preventable disease. The 2020 U.S. Surgeon General’s report addresses this new challenge facing healthcare professionals by focusing on adolescent intervention in the primary care setting (3,9).

E-cigarettes were initially developed under the guidance of harm reduction principles to provide existing smokers with a smokeless, less harmful alternative to conventional cigarettes for the purpose of aiding cessation. However, many researchers and public health officials have cautioned that, without stringent regulations, alternative nicotine products could potentially become a bridge popularizing tobacco use and initiating addiction among young nonsmokers. Meta-analysis of longitudinal studies supports the conclusion that e-cigarettes serve as a gateway to conventional cigarette smoking (25,26). The AAP policy statement also highlights research that young adults are 3.6 times more likely to progress to traditional cigarettes compared to those who never vaped (10). Since the frontal cortex and impulse control are still developing until individuals are in their mid-20s, this represents a period of increased addiction risk. In addition, the increased social acceptance of electronic nicotine delivery products has led to the renormalization of tobacco and nicotine use (25,27).

The popularity of electronic vaporizing cigarettes spurred the development of various forms of e-cigarettes, including a tank system to be filled with e-juice or e-liquid, a solution which is vaporized producing the nicotinic effects smokers crave with the added draw of choosing their favorite candy or fruit flavor (20,22). Widespread popularity of a sleeker device combined with juvenile flavors such as bubble gum to attenuate the harshness of smoking have been cited as contributing factors in e-cigarette’s massive popularity among adolescents and young adults (17,26). Rapid product innovation and diversity of nicotine products have made studying the long-term consequences of vaping difficult. Since their introduction, long-term studies have yet to be done on the detrimental effects of chronic chemical inhalation or safety comparison between smokeless electronic devices and conventional cigarettes. Despite insufficient research, it should be noted that e-cigarette aerosol is not harmless water vapor (7). E-cigarettes can expose users to several chemicals, including nicotine, carbonyl compounds, and volatile organic compounds, known to have adverse systemic health effects (5,16). As generations of e-cigarettes flood the market, newer e-cigarette models boast larger batteries, capable of heating e-juice to higher temperatures, potentially releasing more nicotine while simultaneously forming additional toxins (18). Advancements in design result in a wide variability of size, distribution, and quantity of aerosol particles delivered to the user (28). A study illustrated how the e-liquid solvents, including propylene glycol and glycerin, will react at high temperatures to produce very high levels of formaldehyde, a well-known carcinogen (29). There are additional concerns regarding the flavors added to e-juice. Research is limited but some studies have shown production of acetals and volatile organic compounds with certain flavors.

Public understanding of the dangers of tobacco naturally led many smokers to attempt to quit, but withdrawal symptoms including insomnia, restlessness, mood dysregulation, irritability, anxiety, and intense nicotine cravings often deter motivated patients. The majority of smokers want to quit but may not understand how to approach this daunting task. Support from clinicians, counselors, and other members of the community can drastically improve the likelihood of successful smoking cessation (30-33). Evidence-based strategies have been established and adopted by anti-smoking programs and primary care clinics alike. New products including various forms of nicotine replacement therapies (NRTs) emerged. NRTs may take the form of a 3 mg or 5 mg nicotine lozenge, gum, or transdermal patch and function to reduce cravings by weaning smokers off the addictive compound, attenuating withdrawal symptoms and mitigating cravings (30,34). Research supports smokers who utilize formal assistance or pharmacotherapy are more successful at quitting compared to those who attempted to quit without any resources. In patients with histories of unsuccessful quit attempts, consider combination therapy to provide short-acting and long-acting therapy, effectively utilizing nicotine replacement therapies (NRTs) with varying durations of action (14,31,32). Clinicians should also recommend patients consider behavioral therapy to elucidate psychosocial mechanisms driving their addiction (18,21,34).

Healthcare providers can play a critical role by advising patients about the benefits of quitting and the resources and support available to them. Between 2000 and 2015, less than one-third of U.S. adult smokers reported using cessation aids such as behavioral counseling, support programs, and/or medication (4). On a survey, 70% of smokers see a clinician annually, and majority of them express a desire to quit. However, fewer than 25% of smokers report leaving their appointment with evidence-based options, counseling, or medication (16). Clinicians are responsible for recognizing tobacco use in their patients and intervening when appropriate. Especially within pediatrics, healthcare providers are urged to implement systems for identifying tobacco use among both the patient and parents/caregivers (8,18). Recommendations to pediatricians include inquiring about tobacco use and smoke exposure as a part of health visits, including tobacco use prevention as part of anticipatory guidance, and addressing parent/caregivers’ tobacco dependence as part of pediatric healthcare (10,35). Promising trends, especially in the decline of conventional cigarettes, support continued efforts to mitigate the effects of the tobacco epidemic. As with other chronic diseases, follow-up is critical in monitoring for treatment adherence, especially in populations prone to relapse.

Intervention begins by identifying tobacco use in patients, often recognized only if the physician is vigilant about the signs of nicotine dependence. Interviewing adolescent patients can be simplified by the 5 A’s of addiction intervention: Ask, Advise, Assess, Assist, and Arrange. This memory tool outlines the steps physicians should take in offering support for smoking cessation. Although a handful of patients may be ready to pursue all five A’s in one visit, it is more likely that patients will return multiple times, receiving aspects of care from various healthcare teams or institutions (9,21). Physicians should support the patient at each step, allowing the patient to dictate the pace of progress. Each step is explained in Table 2. Once the patient has expressed a desire to quit, physicians should encourage them to prepare by taking the following steps using the STAR mnemonic. Set a quit date, ideally within 2 to 4 weeks. Tell your family, friends, and coworkers about quitting and ask for their support. Anticipate challenges, including nicotine withdrawal symptoms particularly during the critical first few weeks. Remove tobacco products from your environment prior to quitting to remove temptation (24,36-38)

Table 2: The 5 A’s of Addiction Intervention

Ask all patients about tobacco use	Verify smoking status at every visit
Advise all tobacco users to quit	Urge tobacco users to quit and offer information on the health benefits of cessation. Advice should be clear, strong, and personalized.
Assess the patients willingness to quit	Determine if your patient is willing to quit now, and if not, when they anticipate being able or interested in quitting.
Assist the user with a quit plan and resources	Assist with creating a quit plan, offer medication, and provide resources including counseling for the best chance of success.
Arrange for follow-up to monitor progress	Support during abstinence and monitoring for adverse effects, challenges, and medication adherence.

Advancements in solving the tobacco epidemic are currently being threatened by the advent of new tobacco products. The 2020 U.S. Surgeon General’s report addresses this new challenge facing healthcare professionals and offers suggestions for addressing this novel issue, including lobbying for comprehensive smoke-free laws, expansion of smoking cessation resources, and availability of cessation medications and strategies that have proven successful in the last decade (9,24). Clinicians in primary care are urged to recognize, evaluate, and treat nicotine addiction especially among young adults and adolescents. The potent addictive properties of nicotine make smoking cessation extraordinarily difficult for many patients; therefore, preventing the development of nicotine dependence is much easier than attempting to quit later in life (16). Physician surveillance of tobacco use in young adults can drastically improve health outcomes for future generations.

Questions
1. True/False: Tobacco dependence is considered a pediatric disease.
2. True/False: A majority of life-long smokers begin smoking in their teen years.
3. How is EVALI diagnosed?

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Answers to questions
1. True. Tobacco use and subsequent addiction often begins in adolescence, emphasizing the importance of clinicians identifying tobacco dependence and intervening when appropriate.
2. True. 90% of smokers report beginning smoking at or before age 19.
3. EVALI is a clinical diagnosis with a positive history of e-cigarette use within the last 90 days in the absence of other pulmonary pathology. It is a diagnosis of exclusion, and histopathology typically resembles organizing pneumonia (OP) and/or diffuse alveolar damage (DAD). Symptoms generally include respiratory, gastrointestinal, and constitutional.