Karen M. Wilson, MD, MPH,a Michelle R. Torok, PhD,b,c Binnian Wei, PhD,d Lanqing Wang, PhD,e MarijuanaMichelle Lowary, MS,c Benjamin C.and Blount, PhD eTobacco Coexposure in Hospitalized Children BACKGROUND: abstract
The impact of secondhand marijuana smoke exposure on children is unknown. METHODS: New methods allow for the detection of marijuana smoke exposure in children. We studied children who were hospitalized in Colorado and had a parent participating in a smoking cessation study; all children had urine samples remaining from the original study as well as consent for future research. Parents completed a survey and Δ urine samples were analyzed for cotinine and marijuana metabolites, including 11-hydroxy- 9-tetrahydrocannabinol (COOH-THC), by using liquid chromatography-tandem mass RESULTS: spectrometry. – The median age of the children was 6.0 years (range 0 17 years); 57% were boys. Half (55%) were white, 12% were African American, and 33% were of another race; 39% identified as Hispanic. Approximately 46% had detectable COOH-THC, and 11% had detectable THC. Of those with detectable THC, 3 were teenagers, and 6 were <8 years of age. There were no significant differences in urinary COOH-THC concentrations by age, sex, race and/or ethnicity, or socioeconomic status. Children with positive results for COOH-THC were more likely to have parents who use marijuana daily, smoke marijuana versus other forms of use, use daily in the home, and smoke marijuana in another room if the children CONCLUSIONS: are around compared with smoking outside. Approximately half of the children who qualified for our study had biological evidence of exposure to marijuana. Researchers in studies such as this provide valuable data on secondhand exposure to children from parents using tobacco and marijuana and NIH can inform public health policies to reduce harm.
WHAT’S KNOWN ON THIS SUBJECT: Maternal exposure to marijuana smoke during pregnancy aDepartment of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, New York; bAdult and Child Consortium for Health Outcomes and Research and Delivery Science, School of Medicine, University of Colorado, can cause lingering harm to children. Additionally, Aurora, Colorado; cSection of Pediatric Hospital Medicine, Children’s Hospital Colorado, Aurora, Colorado; legalization increases the likelihood that children dDepartment of Health Behavior, Roswell Park Comprehensive Cancer Center, Buffalo, New York; and eTobacco will be directly exposed to secondhand marijuana and Volatiles Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for smoke, but the extent and consequences of exposure Disease Control and Prevention, Atlanta, Georgia are still unclear. Dr Wilson conceptualized the study, supervised the data collection and analyses, and drafted WHAT THIS STUDY ADDS: We found that 46% of and finalized the manuscript; Dr Torok developed the study methods, analyzed the data, drafted children who were hospitalized in Colorado with the manuscript, and critically revised the manuscript for important intellectual content; parents participating in a smoking cessation study Dr Wei contributed substantially to the conception and design of the study, completed laboratory analysis, and critically revised the manuscript for important intellectual content; Ms Lowary had detectable metabolites of marijuana in their contributed substantially to the conception and design of the study, oversaw the collection of urine. the data, and critically revised the manuscript for important intellectual content; Dr Blount contributed substantially to the conception and design of the study, oversaw laboratory analysis, and critically revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. This trial has been registered at www.clinicaltrials.gov (identifier NCT02281864). DOI: https://doi.org/10.1542/peds.2018-0820 To cite: Wilson KM, Torok MR, Wei B, et al. Marijuana and Tobacco Coexposure in Hospitalized Children. Pediatrics. 2018;142(6):e20180820
Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 142, number 6, December 2018:e20180820 ARTICLE The use of marijuana has been as volatile organic compounds, larger study to test the efficacy of a increasing in both acceptability polycyclic aromatic hydrocarbons,11,12 tobacco smoking cessation program and legality in the past 15 years. and aromatic amines. Studies for parents of children who are In 2013, according to the National in adults have revealed that it is hospitalized. Families were referred ≥ “ Survey on Drug Use and Health, possible to have similar drug effects to the study by using a standard 5.7 million persons aged 12 years as smoking marijuana from intense screening tool ( Does anyone who ” used marijuana on a daily or almost- secondhand13 marijuana smoke lives in your home or who cares daily basis in the past 12 months, exposure, although this has not for your child use tobacco? ) or which was an increase from the 3.1 been demonstrated in children with by provider recommendation for million daily1 or almost-daily users secondhand exposure. Even brief participation; all families were in 2006. As of January 8, 2018, 22 exposure to levels of marijuana recruited after the legalization of states plus Guam allow the legal use secondhand smoke that are similar recreational marijuana in Colorado of marijuana for medical reasons, and to known tobacco secondhand (January 1, 2014). We recruited
8 states plus Washington, District2 of smoke levels impaired vascular parents of children up through Columbia, allow legal adult use. endothelial14 function in an animal the age of 17 years. To be eligible model. Children can be exposed to to participate, the parent had to Although marijuana can be secondhand and thirdhand marijuana be a current tobacco cigarette combusted, aerosolized, or ingested smoke when parents or other smoker (daily or less than daily but as hash oil or leaves, smoked household members smoke indoors, interested in quitting or reducing marijuana is still the most common 3 similar to how children who live with exposure), and the child had to form. A recent analysis of data tobacco smokers have higher tobacco have been admitted to the hospital from the US NHANES revealed that smoke exposure than those living in within the previous 5 days. Informed exclusive daily marijuana users who 15 smoke-free homes. consent was obtained; parents could do not use tobacco have higher levels elect to have their samples and of smoke biomarkers (eg, volatile The couse of marijuana and tobacco research data available for future organic compounds and polycyclic is common. The National Survey research. Both the initial study aromatic hydrocarbons) than on Drug Use and Health revealed 4 ≥ and the secondary analysis were nonusers. Exposure to marijuana that 36% of 18- to 25-year-olds and 11% of 26-year-olds who were approved by the Colorado Multiple smoke chemicals5 extends to adjacent current cigarette smokers were Institutional Review Board. nonusers, as has6 been shown for 16 tobacco smoke. Although most also current marijuana users. In The parent survey included questions states with legal marijuana use Colorado, we studied children who ’ about demographics, secondhand restrict its use in public indoor and were hospitalized for bronchiolitis smoke exposure, tobacco use, and outdoor spaces, they do not have at Children s Hospital Colorado marijuana use and policies. Parent any restrictions on combustible between 2013 and 2015 and found “ marijuana use was assessed with marijuana use in the presence of that the proportion of marijuana the question, Do you currently children. Although the prevalence exposure among children who were ” smoke marijuana every day, some of secondhand marijuana smoke also exposed7 to tobacco smoke was days, or not at all? and household exposure has not been widely 56%. Thus, is it likely that children “ marijuana use was assessed with studied, we recently found that who are exposed to marijuana smoke the question, How often does 16% of young children who were are also exposed to tobacco smoke, ” anyone smoke marijuana in your hospitalized for bronchiolitis in which is known to be harmful. In this home? We collected urine samples Colorado had exposure to marijuana study, we examine the prevalence 7 from each child. For infants, young smoke. and correlates of marijuana smoke exposure in a population of children children, and older children who Although there is research on the who are hospitalized and have a were developmentally disabled, we dangers6 of –secondhand tobacco parent who smokes tobacco and used cotton balls or a bag to collect smoke and8 10 of prenatal marijuana was enrolled in a tobacco smoking in a diaper; older children provided a sample in a cup. Samples were exposure, the impact of cessation program. − ° secondhand marijuana smoke on METHODS mixed, separated into 10 mL aliquots, children has not yet been studied. and frozen at 80 F. Samples There are several studies that Study Population were batched and sent on dry ice indicate that marijuana smoke to the laboratory at the University contains potentially harmful of California, San Francisco for chemicals, including toxic and This is a secondary analysis of data cotinine testing. Samples that were carcinogenic chemicals, such and samples collected as part of a designated for future research were Downloaded from www.aappublications.org/news by guest on September 24, 2021 2 WILSON et al Statistical Analysis sent on dry ice to the Centers for using marijuana; 11.0% of parents Δ Disease Control and Prevention for reported smoking marijuana every Δ We used frequencies and proportions testing of 9-tetrahydrocannabinol day, and 23.2% reported smoking to describe categorical data and (THC), 11-hydroxy- 9- on some days. Smoking was the measures of median (interquartile tetrahydrocannabinol (COOH-THC), most common form of marijuana ranges) or geometric means (95% and cannabidiol. use (30.1%), followed by edibles confidence limits) to describe Analysis of Urinary Tobacco Biomarkers (14.5%) and vaporizers (9.6%). continuous data. For categorical χ Although most parents reported that variables, bivariate analyses were ’ 2 no one ever smokes marijuana inside performed by using tests and – t their homes (84.0%), 7.4% reported Urinary cotinine was analyzed by Fisher s exact tests when indicated. marijuana smoking in the home using liquid chromatography tandem For continuous data, we used tests ’ daily. When asked what happens if mass spectrometry, as previously or Wilcoxon rank tests for bivariate 17 someone wants to smoke marijuana described. The limit of detection analyses. We used Spearman s in the home while children are (LOD) for cotinine was 0.030 ng/ correlation coefficient to evaluate the present, 51.8% reported that there is mL. Laboratory blank and quality- correlation between COOH-THC and no smoking when children are home, control samples were simultaneously cotinine. For bivariate analyses, the 21.7% step outside, and 9.6% smoke processed and analyzed to ensure the outcome variable (COOH-THC level) 15 in another room or on another floor. quality of the analytical results. was dichotomized into below or Analysis of Urinary Marijuana above the LOD. The level of statistical Overall, 45.8% of the children had Biomarkers significance was set at .05. Analyses detectable levels of COOH-THC; 8% were performed by using SAS version also had detectable cannabidiol, 9.4 (SAS Institute, Inc, Cary, NC). and 10.8% had detectable THC, which would be suggestive of active Analysis for marijuana biomarkers RESULTS exposure. For those with detectable was performed by using the method 12 metabolites, the geometric means by Wei et al. Urine samples were – were THC 0.02 (95% confidence equilibrated with isotopically labeled Of the 146 subjects recruited into – interval [CI] 0.01 0.07), COOH-THC internal standards, deconjugated the original study at the time of – 0.016 (95% CI 0.08 0.36), and by using enzymatic and alkaline these analyses, 120 (82%) had cannabidiol 0.39 (95% CI 0.02 9.83). hydrolysis, and extracted by using given consent for future research; – μ Of those with detectable THC, 3 C18 sorbent. The final extracts 83 (69%) of these had a sufficient ≤ were adolescents (14 16 years old); were concentrated, and 10 L of sample remaining for the analysis – the remaining 6 children were 7 each sample was injected into an and were included in the study. ≤ years old. Of those with detectable ultra-high performance liquid The median length of time between THC who were 7 years old, 83% chromatograph and analyzed by admission and urine sample of their parents reported household using tandem mass spectrometry collection was 36 hours. At the time – marijuana use on some days or every under electrospray ionization of hospitalization, the median age of day. The geometric mean cotinine mode. This method has LODs of the children was 6 years (range 1 17 level was 1.0 ng/mL; there was no 0.005, 0.015, and 0.009 ng/mL for years), and 56.6% were boys. Most statistically significant correlation the 3 urinary biomarkers (total (54.9%) were white, 12.2% were P between COOH-THC and cotinine THC, COOH-THC, and cannabidiol, black and/or African American, and levels ( = .18); these results were respectively). THC is the primary 32.9% were of another race; 38.6% not significantly different when psychoactive constituent in identified as being of Hispanic or analyzed without 3 adolescent marijuana, and cannabidiol is the Latino ethnicity. The median age presumed marijuana users (based on second most abundant cannabinoid of the parents was 33 years; most THC levels) and a possible tobacco after THC. Both THC and cannabidiol (54.2%) were married, 56.3% had user (based on urine cotinine level). have short elimination half-lives in at least some college, 22.7% had urine; therefore, their detection often annual incomes of at least $50000, MarriageP status was significantly indicates recent and active exposure. and 61.4% lived in detached homes associated with detectable COOH-THC COOH-THC is the primary metabolite (Table 1). Parents smoked a mean of ( = .02); otherwise, there were no of THC, and its half-life is 3 to 4 days; 11 tobacco cigarettes per day; most statistically significant demographic its presence in urine provides a (83.1%) had also used electronic differences between patients with wider detection window and a more cigarettes at least 1 or 2 times, but COOH-THC above and below the sensitive measure of both active and <4% reported using them daily. LOD (Table 1). Daily parent and/or passive marijuana smoke exposure. Most parents (85.4%) reported ever caregiver smoking of marijuana was Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 142, number 6, December 2018 3 TABLE 1 Child and Parent Demographics and COOH-THC Levels Variables Total (n = 83) ≥LOD COOH-THC
—, not applicable. use, and it requires higher levels18 of exposure for a positive result. In this study, 9 (10.8%) children were positive for detectable levels significantly associated with positiveP use inside the home had detectable of THC. Although 3 of the 9 subjects results for COOH-THC (72.0% vs COOH-THC compared with 66.7% of were adolescents, and potentially ≤ 28% negative for COOH-THC; < those reporting weekly use, 100% marijuana users themselves, 6 of the .01), whereas the use of edibles of those reporting monthly use, THC-positive children were ages 7 was not significantly associated andP 36.8% of those reporting never years, and most had parents who with detectable positive results for smoking marijuana in the home reported marijuana use some days or ( < .001; Table 2). Smoking COOH-THC (58.3% positiveP results every day. Not surprisingly, children for COOH-THC vs 41.7% negative marijuana in another room was whose parents reported smoking results for COOH-THC; = .35). also strongly associated with COOH- marijuana in another room while Regular vaporizer use was also not THC (100% vs 44.2% of those who children were home had detectable significant; 75.0% were positive for reported never smoking when the COOH-THC. Research on secondhand Pchildren are home and 29.4% of and thirdhand tobacco smoke has COOH-THCP compared with 25.0% being negative for COOH-THC those who reported stepping outside; clearly revealed that smoking in = .004). ( = .13). Removing the 3 adolescent the home, even in a different room, presumed users from these analyses DISCUSSION results in19 significant exposure to did not substantively change these children. Parents and caregivers results. All of the children with a who avoid smoking tobacco, marijuana, or both in the home are parent reporting daily marijuana Nearly half of the children who thus likely to reduce exposure to use had detectable COOH-THC along were hospitalized and had a parent infants and children residing there. withP 47.4% of those using some days enrolled in a tobacco smoking and 37.0% of those using not at all cessation program had a biological There are several limitations to ( < .01). Similarly, 100% of children confirmation of marijuana smoke this study. We studied children for whom there was daily marijuana exposure. Secondhand exposure who were hospitalized and had a Downloaded from www.aappublications.org/news by guest on September 24, 2021 4 WILSON et al TABLE 2 Comparison of Parent Report of Marijuana and Tobacco Use and Urine COOH-THC Level Variables Total (n = 83) ≥LOD COOH-THC (n = 38)
Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 142, number 6, December 2018 5 CONCLUSIONS parent who is a cigarette smoker in for future research with those who Colorado, and the results may not did not and found no statistically Almost half of the children with be generalizable to the outpatient significant differences between the 2 parents who were enrolled in a setting and to children whose groups. We assessed urine cotinine tobacco cessation program had parents do not smoke cigarettes, and marijuana metabolites from biological evidence of exposure to especially because we know the samples obtained while the children marijuana. Studies such as couse of marijuana16 and tobacco is were in the hospital; although this provide valuable data on common. We also cannot generalize the median length of time from secondhand exposure in children to states where marijuana is not admission to urine sampling was whose parents use tobacco and legal recreationally or for parents 36 hours, it is possible that there marijuana; future research is who are not willing to consider were some who had been exposed needed to understand the potential quitting smoking. Our sample is before admission but no longer had for harm. small, which limits our ability to do detectable metabolites. Although ABBREVIATIONS further analyses. Participation in this we found that children of married study was dependent on families couples were the least likely to have in the parent study approving their positive results for COOH-THC, the CI: confidence interval data to be used for future research. reasons for this association are Δ ’ COOH-THC: However, we compared demographic unclear and likely confounded by ’ 11-hydroxy- 9-tet- characteristics, children s urinary other factors. Finally, we are unable rahydrocannabinol cotinine, and parents reported to assess whether the exposure to Δ LOD: limit of detection frequency of marijuana smoking marijuana had any impact on the THC: 9-tetrahydrocannabinol between subjects who gave consent health of the children. Accepted for publication Sep 19, 2018 Address correspondence to Karen M. Wilson, MD, MPH, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1198, New York City, NY 10029. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2018 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: Funded by Children’s Hospital Colorado Research Institute, the Icahn School of Medicine at Mount Sinai, the National Cancer Institute (grant R01 CA181207), and the Centers for Disease Control and Prevention. Additional support for the cotinine analysis was provided by the National Institute on Drug Abuse (grant P30 DA012393), the National Center for Research Resources (grant S10 RR026437), and the Flight Attendant Medical Research Institute through grants to the University of California, San Francisco Bland Lane Center of Excellence on Secondhand Smoke and the American Academy of Pediatrics Julius B. Richmond Center of Excellence. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, the National Cancer Institute, or the Flight Attendant Medical Research Institute. Funded by the National Institutes of Health (NIH). POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
REFERENCES 1. Substance Abuse and Mental Health 3. Schauer GL, King BA, Bunnell RE, consequences of involuntary exposure Services Administration. Results from Promoff G, McAfee TA. Toking, vaping, to tobacco smoke. Am J Prev Med. the 2013 national survey on drug and eating for health or fun: marijuana 2007;32(6):542–543 use and health: summary of national use patterns in adults, U.S., 2014. Am J 7. Wilson KM, Torok MR, Wei B, et al. findings. NSDUH series H-48, HHS Prev Med. 2016;50(1):1–8 Detecting biomarkers of secondhand Publication No. (SMA) 14-4863. 2014. 4. Wei B, Wang L, Blount BC. Analysis of marijuana smoke in young children. Available at: www.samhsa.gov/data/ cannabinoids and their metabolites Pediatr Res. 2017;81(4):589–592 sites/default/files/NSDUHresultsPDFWH in human urine. Anal Chem. 8. Jutras-Aswad D, DiNieri JA, Harkany T, TML2013/Web/NSDUHresults2013.pdf. 2015;87(20):10183–10187 Hurd YL. Neurobiological consequences Accessed September 28, 2015 5. Cone EJ, Bigelow GE, Herrmann of maternal cannabis on human fetal 2. Governing the States and Localities. ES, et al. Non-smoker exposure to development and its neuropsychiatric State marijuana laws in 2018 map. secondhand cannabis smoke. I. Urine outcome. Eur Arch Psychiatry Clin 2018. Available at: www.governing.com/ screening and confirmation results. Neurosci. 2009;259(7):395–412 gov-data/state-marijuana-laws-map- J Anal Toxicol. 2015;39(1):1–12 9. Smith AM, Mioduszewski O, Hatchard medical-recreational.html. Accessed 6. Moritsugu KP. The 2006 Report of T, Byron-Alhassan A, Fall C, Fried PA. February 16, 2018 the Surgeon General: the health Prenatal marijuana exposure impacts
Downloaded from www.aappublications.org/news by guest on September 24, 2021 6 WILSON et al executive functioning into young secondhand cannabis smoke. III. Oral 17. Jacob P III, Yu L, Duan M, Ramos adulthood: an fMRI study. Neurotoxicol fluid and blood drug concentrations L, Yturralde O, Benowitz NL. Teratol. 2016;58:53–59 and corresponding subjective effects. Determination of the nicotine 10. Fried PA, Watkinson B, Gray R. J Anal Toxicol. 2015;39(7):497–509 metabolites cotinine and trans-3′- Growth from birth to early 14. Wang X, Derakhshandeh R, Liu J, et al. hydroxycotinine in biologic fluids adolescence in offspring prenatally One minute of marijuana secondhand of smokers and non-smokers using exposed to cigarettes and smoke exposure substantially impairs liquid chromatography-tandem mass marijuana. Neurotoxicol Teratol. vascular endothelial function. J Am spectrometry: biomarkers for tobacco 1999;21(5):513–525 Heart Assoc. 2016;5(8):e003858 smoke exposure and for phenotyping cytochrome P450 2A6 activity. 11. Moir D, Rickert WS, Levasseur G, 15. Matt GE, Quintana PJ, Hovell MF, et al. J Chromatogr B Analyt Technol Biomed et al. A comparison of mainstream and Households contaminated by Life Sci. 2011;879(3–4):267–276 sidestream marijuana and tobacco environmental tobacco smoke: sources cigarette smoke produced under two of infant exposures. Tob Control. 18. Huestis MA. Pharmacokinetics and machine smoking conditions. Chem 2004;13(1):29–37 metabolism of the plant cannabinoids, Res Toxicol. 2008;21(2):494–502 delta9-tetrahydrocannabinol, 16. Richter L, Pugh BS, Smith PH, Ball SA. cannabidiol and cannabinol. Handb Exp 12. Owen KP, Sutter ME, Albertson The co-occurrence of nicotine and Pharmacol. 2005;(168):657–690 TE. Marijuana: respiratory tract other substance use and addiction effects. Clin Rev Allergy Immunol. among youth and adults in the United 19. Apelber g BJ, Hepp LM, Avila-Tang E, 2014;46(1):65–81 States: implications for research, et al. Environmental monitoring of 13. Cone EJ, Bigelow GE, Herrmann practice, and policy. Am J Drug Alcohol secondhand smoke exposure. Tob ES, et al. Nonsmoker exposure to Abuse. 2017;43(2):132–145 Control. 2013;22(3):147–155
Downloaded from www.aappublications.org/news by guest on September 24, 2021 PEDIATRICS Volume 142, number 6, December 2018 7 Marijuana and Tobacco Coexposure in Hospitalized Children Karen M. Wilson, Michelle R. Torok, Binnian Wei, Lanqing Wang, Michelle Lowary and Benjamin C. Blount Pediatrics originally published online November 19, 2018;
Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2018/11/15/peds.2 018-0820 References This article cites 17 articles, 3 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2018/11/15/peds.2 018-0820#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Environmental Health http://www.aappublications.org/cgi/collection/environmental_health_ sub Injury, Violence & Poison Prevention http://www.aappublications.org/cgi/collection/injury_violence_-_poi son_prevention_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml
Downloaded from www.aappublications.org/news by guest on September 24, 2021 Marijuana and Tobacco Coexposure in Hospitalized Children Karen M. Wilson, Michelle R. Torok, Binnian Wei, Lanqing Wang, Michelle Lowary and Benjamin C. Blount Pediatrics originally published online November 19, 2018;
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2018/11/15/peds.2018-0820
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.
Downloaded from www.aappublications.org/news by guest on September 24, 2021