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January 6, 2020

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.

References

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.

January 5, 2020

Adolescence is a developmental inflection point replete with vast changes across biological, social and psychological domains. Not surprisingly, it is arguably one of the most misunderstood periods of human development. Of the many misconceptions regarding adolescence, few are more ubiquitous than the notion that it is a time of inevitable depression and prolonged psychological turmoil. While epidemiologically, the teenage years represent an increased risk for depression, the vast majority of adolescents report few to no depression symptoms. It is all too common for parents and caregivers to mislabel clinically significant signs of depression as mere “hormones” or “normal teenage stuff.” Although depression is certainly not inevitable during adolescence, recent research has identified symptom profile patterns unique to teenagers.

When we consider depression as a clinical construct, we think of a constellation of various symptoms from depressed mood, inability to experience pleasure, to sleep difficulties and changes in appetite. Given the many signs and symptoms of depression, there exists a high degree of variability among diagnostic profiles. Among adolescents, individual differences greatly impact the cognitive, emotional and behavioral manifestation of depression. To improve clinical assessment of depression, researchers have taken a keen interest in better understanding common symptom patterns in adolescent depression. In a 2019 study in the Journal of Clinical Child Psychology, researchers from The University of Texas at Austin examined adolescent depression using a large sample of roughly 1,500 adolescents ages 13-19. The researchers were interested in which particular symptoms were most important with regard to overall distress and associated functional impairment.  In other words, what is the true “core” of adolescent depression. Results indicated that self-hatred and loneliness were the most central symptoms in adolescent depression, followed by sadness and pessimism. The results of study illuminate a key difference in depression symptom manifestation between adolescents and adults, with depressed mood and anhedonia being more central to adult depression.

From a developmental perspective, these findings make sense given that identity formation is a key task during adolescence. Many adolescents struggle during these years to better understand themselves, clarify their values, and develop a more robust sense of self. A predisposition toward depression in conjunction with this challenging developmental task can often lead to feelings of self-hatred. Loneliness is also logical from a developmental perspective given the importance of social engagement during adolescence. As children enter the teenage years, the drive for social affiliation and building new peer relationships increases exponentially. Adolescents are therefore more likely to experience more intense feelings of loneliness when encountering struggles with social engagement.   

Pediatric providers are in a unique position to recognize early warning signs of adolescent depression. Most providers rely on a summative score on a self-report measure to evaluate adolescent depression. While these measures have great economic utility, relying on a sum total score fails to take into account that some symptoms are simply more important than others. In line with this, it may be prudent for pediatric providers to assess for signs of self-hatred, perceived social support, and social connectedness. Assessing these important areas can help providers zero in on the possible core of adolescent depression.


About the Author

Sam Marzouk, Ph.D., L.P. is a pediatric psychologist and specialist in adolescent mental health. Dr. Marzouk completed his postdoctoral training at Children’s Minnesota and is currently the owner of Promethean Psychology in Edina, Minnesota. A strong advocate for evidence-based psychology, Dr. Marzouk is passionate about translating research into clinical practice to empower children, adolescents and families.   

Each year, MNAAP brings together more than 100 residents, community pediatricians and medical students to discuss and advocate for issues that have a direct effect on the health of Minnesota children. We want you to join us to make 2020 the most impactful year yet.

Following a brief primer on the chapter’s positions, we’ll hear from our state lobbyist and key legislators about specific child health issues being debated. You’ll have the opportunity to weigh in and discuss priority issues with your own legislators as well.

See an agenda for the day here and plan to join us on Monday, March 23!  Register now!

When an engaging group of MNAAP senior pediatricians gathered together at The Wedge Table in Minneapolis on Dec. 5, the conversation spanned everything from ways to stay connected and give back, to using social media, to memories of their experiences treating vaccine-preventable diseases.

The MNAAP senior pediatricians’ group was recently revived after a brief lapse in regular meetings. (Pictured from left to right) Gathered in December were (front row) Bea Murray, Karen Olness, Tom Scott, Paula Kelly, Linda Thompson (back row) Carolyn Levitt, Roger Sheldon, Ted Jewett, Mark Nupen, Kris Benson.

The attendees are all retired, and many continue to stay connected with medicine and child advocacy efforts. One member mused that pediatricians currently in practice should consider “what’s next” for them before they retire. “Pick a path before retirement!”

Hoping to gather some pearls of wisdom about the importance of immunizations, the group was asked to think back to their years in practice before vaccines prevented many of life-threatening childhood diseases.

The differences they described underscore the importance of strengthening childhood vaccination laws in Minnesota.

The group plans to meet again in early March. If you are a senior pediatrician interested in joining, email debilzan@mnaap.org.

Memories of treating vaccine-preventable diseases…

“You used to see chicken pox on a daily basis. But now, you show that to a resident and they might have no idea.”

“We were trained to treat all these diseases doing spinal taps, and then [with immunizations] poof, all of them were gone! That’s what most of your hospitalizations were for. They were gone, literally.”

“We used to have three to five cases of meningitis in the ER out in Denver. I mean it was just horrible. And I remember my first medical school rotation, there was this little kid with H flu meningitis. The parents had left on Halloween night to trick or treat with their other kids, and came back, and that baby was seizing. I remember that like it was yesterday.”

 

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