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November 7, 2019

Vaping—Seeking Clarity in a Time of Uncertainty

Author Affiliations
  • 1Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
  • 2Section of General Internal Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
  • 3Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
JAMA. Published online November 7, 2019. doi:https://doi.org/10.1001/jama.2019.16493

As of October 28, 2019, 49 states have reported more than 1600 possible cases of severe pulmonary disease related to vaping—the inhalation of a heated, aerosolized solution—to the Centers for Disease Control and Prevention (CDC).1 To date, 34 deaths have been attributed to e-cigarette, or vaping, product use–associated lung injury (EVALI). This has resulted in a recommendation from the CDC that the public avoid the use of e-cigarette products, a proposed federal prohibition on certain products and flavors, and much uncertainty on the part of patients and clinicians. In the midst of this uncertainty, it is important to try to provide some clarity.

Vaping is typically associated with the use of nicotine e-cigarettes, although it is not a uniform process and involves a variety of devices, substances, and practices, each of which can cause vaping-related harms. Specifically, “closed-system” vaping devices have self-contained e-liquids (cartridges or pods) and are not meant for modifications (eg, JUUL), whereas “open-system” vaping devices can be modified, allowing users to insert a range of e-liquids, including cannabinoids. The health effects of vaping are likely to vary depending on the device, the substance being vaped, and the amount and type of exposure. For well-established nicotine e-liquids, vaping has been shown to deliver substantially lower concentrations of toxic substances per puff than conventional cigarette smoking.2 However, this may not apply to modified e-liquids, and little is known about the health effects of vaping cannabinoids.

Three recently published case series from separate regions of the United States describe patient presentations of EVALI. In the largest series from Illinois and Wisconsin,3 84% of the 53 cases of EVALI involved the use of tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana. Multiple patterns of lung injury have been reported, and many cases of EVALI have been suggestive of acute lipoid pneumonia, a relatively rare acute inflammatory reaction resulting from inhalation of oil.4 Other observed pathologic patterns of lung injury have been nonspecific, but suggestive of chemical pneumonitis.5 Reports that many of the substances contained vitamin E acetate are currently being followed by the CDC and the US Food and Drug Administration (FDA). However, investigators are still gathering data surrounding this outbreak, such as which devices were used, which products were vaped, when and by whom the devices and e-liquids were modified, the precise nature of each exposure (especially regarding duration of use), and the source (legal or illegal) of the products. Moreover, patients’ reports may be unreliable, particularly if illegal modifications and illicit substances are involved.

While it seems that the number of individuals presenting with EVALI increased quickly, suggesting new or emerging products, it is possible that this apparent increase represents greater surveillance for and reporting of a phenomenon that has been present all along. Responding to this uncertainty, the CDC has issued broad recommendations1 for individuals that, as of October 28, 2019, include advice to (1) avoid vaping THC; (2) avoid modified or street-bought vaping products; (3) consider refraining from use of all e-cigarette or vaping products; (4) not return to smoking cigarettes among adults who are using e-cigarettes for the purpose of smoking cessation and to consider the use of FDA-approved nicotine replacement therapies; and (5) monitor for symptoms similar to those previously reported if you are an adult using e-cigarettes or vaping products. Irrespective of the ongoing investigation, children, young adults, women who are pregnant, and adults who do not currently use tobacco products should avoid vaping.1

What are the implications of these observations and health guidance? First, the risks of different vaping substances, particularly regarding THC, nicotine, and other additives, need to be more clearly distinguished. Even though there have been sporadic reports of acute lung injury involving nicotine e-cigarettes, these products have been available since 2007 without frequent reports of severe toxicity. The Illinois and Wisconsin case series3 noted a near doubling of the rate of severe acute lung injury identified by syndromic surveillance between June 1, 2019, and August 15, 2019, compared with the same period in 2018. This pattern suggests a new phenomenon, potentially consistent with an increase in use of illegal or user-modified nicotine e-products or non-nicotine substances. The vast majority of recently published reports of individuals with EVALI have involved THC.

In this context, chemicals and additives in marijuana and THC oils are important. Even though smoking marijuana is known to deliver a large amount of toxins to the lung,6 little is known about the effects of marijuana and THC when vaporized and inhaled. An unregulated marketplace further complicates the situation because risks may depend on factors in the supply chain, delivery devices, inhalation practices, medical vulnerability, or other variables. Current cases of EVALI could stem from marijuana/THC, distinct additives in these e-liquids, or both. Rapid and robust research is needed to clarify these risks and provide guidance.

Second, as devastating as these instances of EVALI are for the individuals involved, it is important to keep the scale of these reports in perspective. One estimate suggests that nearly 11 million US adults use nicotine e-cigarettes,7 and a smaller number vape marijuana. Considering this scale relative to the number of EVALI cases, the greater public health concern is whether individuals who participate in vaping are at increased risk of developing chronic lung disease over time,8 similar to smokers who do not typically develop medical disease until after many years of persistent use. Vigilance is critical, even after a full understanding of these individuals with EVALI is reached. Long-term longitudinal studies of exposure and outcomes associated with vaping nicotine, marijuana, and other substances will be essential for understanding the true risks of these behaviors.

Third, it is critical to keep focus on the dominant public health problem: combustible cigarette smoking. Significant improvements have occurred in tobacco control, and population smoking prevalence has been reduced to its lowest level. This has occurred despite the rapid increase in e-cigarette use, and perhaps even, in part, because of it.9 Yet smoking remains the leading cause of preventable death in the United States, with large disparities in smoking and smoking-related health outcomes by socioeconomic and mental health status. Some former combustible cigarette smokers may use e-cigarettes chronically as a nicotine delivery system to maintain smoking abstinence. These smokers may include individuals who had no success with conventional tobacco cessation strategies. It is important that ex-cigarette smokers who use e-cigarettes do not revert to conventional cigarettes, which likely pose much higher absolute risks of adverse health outcomes than nicotine e-cigarettes.

How should physicians approach the vaping problem in clinical practice? Clinicians could start by routinely asking patients about vaping. Important follow-up questions to a positive response include gathering information about which devices are being used and whether modifications have been made, what substances and additives are being vaped, where the products were obtained, the frequency of use, the reasons for use, the willingness to discontinue use, and the risk of relapse to conventional cigarettes if vaping is ceased. Products that are illegally purchased, modified, or of unknown quality or source to users may pose a higher risk of toxicity than those purchased from mainstream vendors, and clinicians should counsel their patients to this effect. Patient motivation to discontinue vaping may provide the opportunity for clinicians to engage patients in comprehensive care, including specialty addiction referral, behavioral counseling, and more thorough psychiatric evaluation if warranted.

Special care must be taken when communicating with adult smokers who switched to nicotine vaping or fail to respond to conventional tobacco cessation strategies. Chronic cigarette smoking is still likely to be more harmful than chronic nicotine vaping, and those who choose to vape should avoid devices or e-liquids that are modified or cannot be sold legally in the United States. These patients should be offered standard tobacco cessation strategies to try to wean off vaping, such as nicotine replacement (patches, gum, lozenges, sprays, or inhalers) or varenicline or bupropion, in addition to behavioral counseling. However, ensuring that these patients do not return to combustible cigarettes must be the priority. Nicotine vaping may reduce harm if it prevents these individuals from smoking. Longitudinal analyses and randomized trials with extended follow-up will help to more precisely understand the benefits and risks.

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Article Information

Corresponding Author: Stephen R. Baldassarri, MD, MHS, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, 300 Cedar St, TAC-455 S, New Haven, CT 06520 (stephen.baldassarri@yale.edu).

Published Online: November 7, 2019. doi:10.1001/jama.2019.16493

Conflict of Interest Disclosures: Dr Baldassarri reported receiving grants from the National Institute on Drug Abuse (K23DA045957). Dr Fiellin reported receiving grants from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism and personal fees from American Society of Addiction Medicine, the American Academy of Addiction Psychiatry, Boston University, and the University of Kentucky. No other disclosures were reported.

Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. Centers for Disease Control and Prevention website. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html. Updated October 25, 2019. Accessed October 28, 2019.
Goniewicz  ML, Knysak  J, Gawron  M,  et al.  Levels of selected carcinogens and toxicants in vapour from electronic cigarettes.  Tob Control. 2014;23(2):133-139. doi:10.1136/tobaccocontrol-2012-050859PubMedGoogle ScholarCrossref
Layden  JE, Ghinai  I, Pray  I,  et al.  Pulmonary illness related to e-cigarette use in Illinois and Wisconsin: preliminary report  [published online September 6, 2019].  N Engl J Med. doi:10.1056/NEJMoa1911614PubMedGoogle Scholar
Davidson  K, Brancato  A, Heetderks  P,  et al.  Outbreak of electronic-cigarette-associated acute lipoid pneumonia: North Carolina, July-August 2019.  MMWR Morb Mortal Wkly Rep. 2019;68(36):784-786. doi:10.15585/mmwr.mm6836e1PubMedGoogle ScholarCrossref
Butt  YM, Smith  ML, Tazelaar  HD,  et al.  Pathology of vaping-associated lung injury  [published online October 2, 2019].  N Engl J Med. doi:10.1056/NEJMc1913069PubMedGoogle Scholar
Wu  TC, Tashkin  DP, Djahed  B, Rose  JE.  Pulmonary hazards of smoking marijuana as compared with tobacco.  N Engl J Med. 1988;318(6):347-351. doi:10.1056/NEJM198802113180603PubMedGoogle ScholarCrossref
Mirbolouk  M, Charkhchi  P, Kianoush  S,  et al.  Prevalence and distribution of e-cigarette use among US adults: behavioral risk factor surveillance system, 2016.  Ann Intern Med. 2018;169(7):429-438. doi:10.7326/M17-3440PubMedGoogle ScholarCrossref
Ghosh  A, Coakley  RD, Ghio  AJ,  et al.  Chronic e-cigarette use increases neutrophil elastase and matrix metalloprotease levels in the lung.  Am J Respir Crit Care Med. 2019. doi:10.1164/rccm.201903-0615OCPubMedGoogle Scholar
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