In the summer of 2019, the pulmonologists at Children’s Minnesota treated and reported the first cases of e-cigarette, or vaping, product use–associated lung injury (EVALI) in Minnesota. By the beginning of December 2019, the Centers for Disease Control and Prevention (CDC) had received more than 2,290 reports of EVALI (including 34 deaths) from all state health departments in the continental U.S., Hawaii, and the U.S. Virgin Islands, and the Minnesota Department of Health (MDH) has characterized 125 cases of EVALI (defined as “confirmed” or “probable”) with three associated deaths in at least 26 counties with dozens more cases which are undergoing further review. While this condition has mainly been recognized in adolescents and young adults, it has been reported in people ages 13-75 years.
A recent report of clinician and CDC expert opinion regarding this epidemic was published to help outline common presenting symptoms, clinical workup, course of illness, treatment, and potential associated sequelae. All patients have reported some e-cigarette use in the past 90 days. Most patients report marijuana-derived tetrahydrocannabinol (THC) concentrate vaping, many report use of both THC concentrate and nicotine products, and a minority have reported isolated vaping of nicotine or non-nicotine/non-THC products alone.
Almost universally, patients report respiratory symptoms, such as shortness of breath, cough, and chest pain. The majority of patients have had some mild gastrointestinal symptoms, including: nausea, vomiting, diarrhea, and/or abdominal pain. Common constitutional symptoms include fever, malaise, and loss of appetite. All patients with EVALI have abnormal chest imaging findings, typically bilateral opacification, often with some evidence of subpleural sparing. Laboratory studies often demonstrate high inflammatory markers (c-reactive protein, erythrocyte sedimentation rate, and white blood count), with or without mildly abnormal hepatic injury markers. Apart from cough, lung exam is often unremarkable. Most patients have been hospitalized, roughly one third have required the intensive care unit. Bronchoscopy and on
occasion lung biopsy have helped rule out other causes of acute lung injury, however the histopathologic categorization of this injury has been challenging and variable, most often with a combination of acute pneumonitis and diffuse alveolar damage.
Approximately 88 percent of nationally reported cases were treated with systemic steroids, although the natural history of this disease is unknown. Rationale for this treatment approach and how to approach milder cases remains challenging in this field. Notably, the majority of cases in our state were managed for anxiety, depression, or other mental health concerns prior to their severe lung disease.
In follow up, we have witnessed our patients struggle with withdrawal, anxiety, depression, addiction, social navigation challenges, and isolation. Concern for exposure relapse, undertreated (or self-treated) mental health concerns, unknown long-term pulmonary sequelae, and potential secondary adrenal insufficiency have necessitated a multidisciplinary team approach to this disease.
The CDC case definition of this disease has been reliant upon abnormal chest imaging with compatible history and other findings. A thorough work up and absence of other concurrent disease processes (such as infection) qualifies for a CDC surveillance case designation of “confirmed.”
A case designation of “probable” has been reserved for cases with limited workup or an additional active disease process not thought to be the sole cause of the lung disease (such as a known otitis media, stomach flu or otherwise). These are helpful distinctions for CDC surveillance but may cause confusion for clinical coding purposes. The CDC has offered some ICD-10 early guidance but further specification may change overtime with the potential introduction of new codes.
Incidentally, what this disease has clarified is that in many vaping patients who do not have EVALI, symptoms related to vaping (cough, shortness of breath) may occur. Preliminary data from the 2019 Minnesota Student Survey suggest one in four Minnesota 11th graders partake in e-cigarette usage.
It is our hope that the 2020 Youth Tobacco Survey might specifically expand the questioning surrounding THC usage to include modality (e.g. vaping, dabbing, edibles). We further acknowledge that familiarity with the management of nicotine and THC addiction needs to expand, looking to our medical colleagues within and beyond pediatrics to gain expertise. Early research into e-cigarette usage suggests the chemicals inhaled can cause immune dysregulation. Studies of real-world patterns of use of these products and their degradation with variable heating may further inform us of the consequences of vaping. The recognition of vaping-related symptoms in non-EVALI patients may lead to a better understanding of the effects of usage of these products.
In collaboration with local clinical providers, MDH recently developed an algorithm intended to assist health care providers with rapid recognition and evaluation of EVALI and can be found at www.health.state.mn.us/diseases/lunginjuries/docs/vapingalgorithm.pdf. Cases need to continue to be identified to avoid risk of potential relapse and your pediatric pulmonologists continue to offer their support. For more information regarding EVALI, please consult the references listed to below.
1) Siegel D, Jatlaoui T, Koumans E,et al. Update: Interim guidance for jealthcare providers caring for patients with suspected e-cigarette, or vaping, product use associated lung injury-United States, October, 2019. MMWR Morb Mortal Wkly Rep 2019; 68:1-9.
2) Severe lung injury associated with vaping algorithm. Minnesota Department of Health. Website accessed 11/5/19. https://www.health.state.mn.us/diseases/lunginjuries/docs/vapingalgorithm.pdf
3) Cullen KA, Ambrose BK, Gentzke AS, Apelberg BJ, Jamal A, King BA. Notes from the field: Use of electronic cigarettes and any tobacco product among middle and high school students –United States, 2011-2018. MMWR 2018;67:1276-1277.
4) 2019 Minnesota Student Survey: E-cigarette and cigarette findings e-cigarette use continues to escalate among youth. Minnesota Department of Health. https://www.health.state.mn.us/communities/tobacco/data/docs/2019_mss_tobacco.pdf
5) Meier MH, Docherty M, Leischow SJ, Grimm KJ, Pardini D. Cannabis concentrate use in adolescents. Pediatrics 2019;144(3). Pii:e20190338.
6) Moritz ED, Zapata LB, Lekiachvili A, et al. Update: Characteristics of patients in a national outbreak of e-cigarette, or vaping, product use –associated lung injuries –United States, October 2019. MMWR Morb Mortal Wkly Rep 2019;68:985-989.
7) Meehan-Atrash J, Luo W, Strongin RM. Toxicant formation in dabbing: the terpene story. ACS Omega. 2017;2(9):6112-6117.
8) Clapp PW, Pawlak EA, LackeyJT, et al. Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function. Am J Physiol Lung Cell Mol Physiol 2017;313(2):L278-L292.
About the Authors
Anne Griffiths, MD, FAAP, is a pediatric pulmonologist with Children’s Minnesota and Children’s Respiratory and Critical Care Specialists, P.A.; Melinda Pierce, MD, FAAP, is a pediatric endocrinologist with Children’s Minnesota; Damon Olson, MD, is a pediatric pathologist with Children’s Minnesota; and Brooke Moore, MD, MPH, is a pediatric pulmonologist with Children’s Minnesota and Children’s Respiratory and Critical Care Specialists, P.A.