Assessment of Nicotine and Cannabis Vaping and Respiratory Symptoms in Young Adults

This cross-sectional study examines whether nicotine vaping and cannabis vaping are associated with bronchitic symptoms, wheeze, and shortness of breath in young adults.


Introduction
The increasing prevalence of nicotine and cannabis vaping (ie, inhalation of aerosolized nicotine or cannabis containing e-liquids or oils) among youth and young adults is a serious public health concern. 1-4 E-liquid aerosols contain many known respiratory toxicants, including volatile carbonyls (eg, aldehydes), furans, and metals, 5 that likely adversely affect lung health with prolonged exposure. 6 Because of the lack of regulation for the manufacture of nicotine and cannabis vaping devices, many e-liquids contain flavorings and other additives that may adversely affect respiratory health. For example, vitamin E acetate has been identified as an additive in tetrahydrocannabinol (THC)-containing e-liquids and played a role in the 2019 outbreak of e-cigarette and vapingassociated lung injury. 7 This outbreak demonstrated that the health outcomes associated with vaping are not well understood and emphasized the urgent need to understand the implications of nicotine and cannabis vaping for respiratory health.
Experimental studies show that exposure to nicotine and cannabis containing e-liquid aerosols harm the respiratory system; however, human observational research on respiratory symptoms associated with vaping are limited. 6 Some observational and epidemiologic studies have reported associations between nicotine vaping and chronic respiratory outcomes (eg, chronic cough, phlegm, bronchitis, asthma) among both adolescents and adults that are independent of combustible cigarette use. 6,8,9 However, these studies relied on data collected prior to the emergence of a new class of vaping products (ie, pod mods such as JUUL [JUUL Labs, Inc]) that use a salt-based nicotine formulation and have other chemical constituents that differ from previously used nicotine vaping devices. It is also unclear if these associations are independent of cannabis vaping, a method of cannabis administration that has recently gained popularity among youth and young adults. 10 Very little is known about the respiratory health outcomes associated with vaping liquid hash oil and other highly concentrated forms of THC, the psychoactive component of cannabis. Existing research on the respiratory health outcomes associated with cannabis has focused on combustible, smoked cannabis; several observational studies suggest that frequent combustible cannabis smoking is associated with increased odds of shortness of breath, wheeze, and bronchitic symptoms. [11][12][13][14][15] Additional research is needed to assess the implications of other methods of cannabis administration, particularly cannabis vaping, for respiratory health. The present study examined associations between both nicotine and cannabis vaping and respiratory symptoms among young adults in Southern Californian from 2018 through 2019. Level of exposure to nicotine and cannabis vaping are examined in relation to (1) bronchitic symptoms, (2) wheeze, and (3) shortness of breath.

Analytic Sample
Data are from the Happiness and Health Study, 16 a sample of young adults originally recruited from high schools throughout Southern California. Data for the current study were collected from June 2018 to October 2019, 1 year after participants graduated from high school. A total of 2553 participants provided complete data on lifetime, past 6-month, and past 30-day vaping (75% participation rate). Of these participants, 2389 (94%) provided complete data for shortness of breath, 2396 (94%) provided complete data for wheeze, and 2194 (86%) provided complete data for chronic bronchitis. Participants who did not provide any respiratory health data were less likely to

Level of Nicotine and Cannabis Vaping
Participants responded to the question, "Have you ever used the follow substances in your life?" Specific substances included any e-cigarette with nicotine, JUUL or similar device, another electronic vaping device, or an electronic device to vape THC or hash oil/dabs (eg, wax, shatter, budder, and butane hash oil), cigarettes, smoking marijuana, and blunts (questionnaire is available in the eAppendix in the Supplement). Response options included no, yes, yes but not in the last 6 months, or yes in the last 6 months. The term dabs refers to vaping concentrated cannabis. 17,18 For each question, response options were no, yes but not in the last 6 months, or yes in the last 6 months.
Participants who reported using the substance within the last 6 months were then asked to indicate how many total days within the past month they used that substance. Response options included 0 days, 1 or 2 days, 3 to 5 days, 6 to 9 days, 10 to 19 days, 20 to 29 days, and all 30 days. Participants who responded "no" or "yes but not in the last 6 months" to the first question did not receive questions about use in the last month.

Respiratory Outcomes
Based on previous reports of respiratory symptoms among individuals who vape nicotine, 6,9 we assessed 3 different respiratory outcomes: bronchitic symptoms, wheeze, and shortness of breath.
Given the heterogeneity in the pathology of these respiratory symptoms, each outcome was examined separately. Bronchitic symptoms represent a clinical condition reflecting irritant exposure, wheeze is characteristic of bronchoconstriction, and shortness of breath is nonspecific but may reflect bronchiolitis obliterans, which has been associated with the diketones present in e-liquids. 19 Wheeze was chosen as a main respiratory outcome over an asthma diagnosis because most asthma has onset in early life, before the initiation of vaping or smoking. Therefore, wheeze is considered to be a better reflection of current respiratory health outcomes.
To assess bronchitic symptoms, participants reported whether they had (1) daily cough in the morning for 3 months in a row, (2) daily cough at other times of the day for 3 months in a row, (3) congestion or phlegm other than when accompanied by a cold, and (4) bronchitis in the past 12 months. Participants were considered to have bronchitic symptoms if they reported having any of the 4 symptoms. 6,9 For wheeze, participants reported whether they had experienced wheezing or whistling in the chest during the previous 12 months (yes or no). For shortness of breath, participants reported whether they had been troubled by shortness of breath when hurrying on level ground or walking up a slight hill (yes or no).

Covariates
Sociodemographic characteristics, as well as level of cigarette and combustible cannabis smoking were included in the analysis as covariates (eAppendix in the Supplement ). To assess current personal financial status, participants were asked, "Considering your own income and the income from any other people who help you, how would you describe your overall personal financial situation?" Response options included: "live comfortably," "meet needs with a little left," "just meet basic expenses," and "do not meet basic expenses." Level of cigarette smoking and combustible cannabis use (ie, marijuana cigarettes, joints, blunts) were assessed and recoded in the same way as nicotine and cannabis vaping. Two separate 5-level variables reflected never use (0), used in the lifetime but not in the past 6 months (1), used in the past 6 months but not in the past 30 days (2), used 1 or 2 days in the past 30 days (3), used 3 or more days in the past 30 days (4).

Statistical Analyses
A series of logistic regression models were used to examine the associations between the level of nicotine and cannabis vaping with shortness of breath, wheeze, and symptoms of bronchitis in separate models. First, models were adjusted for sociodemographic characteristics including age, sex, race/ethnicity, personal financial status, and BMI. Next, models that were simultaneously adjusting for both nicotine and cannabis vaping examined associations of vaping with bronchitic symptoms, wheeze, and shortness of breath. These models additionally adjusted for cigarette smoking and combustible cannabis use in order to further assess the independent implications of each substance and the method of administration. Two-sided P < .05 was considered to be statistically significant. Results are presented as adjusted odds ratios (aORs) and 95% confidence intervals. Benjamini-Hochberg adjusted P values were used to correct for multiple 2-tailed tests.
Analyses were performed using SAS software, version 9.4 (SAS Institute, Inc).

Results
Among the 2553 participants included in the analytic sample, 1477 were female (57.9%), with a mean

Respiratory Health Outcomes and Levels of Nicotine and Cannabis Vaping
Overall  Table 2).

Associations of Nicotine and Cannabis Vaping With Respiratory Health Symptoms
Details on the associations of nicotine and cannabis vaping with bronchitic symptoms, wheeze, and shortness of breath are presented in Table 3.
When adjusting for sociodemographic characteristics only, vaping nicotine 3 days or more in the past 30 days was associated with increased odds of bronchitic symptoms (aOR, 1.78; 95% CI,   Abbreviation: aOR, adjusted odds ratio. a Associations of nicotine and cannabis vaping with bronchitic symptoms, wheeze, and shortness of breath, adjusting for sociodemographic factors including sex, age, race/ ethnicity, personal financial status, and body mass index (calculated as weight in kilograms divided by height in meters squared). Each respiratory health outcome was modeled separately by exposure. All available data were used in each model; samples vary between models due to missing data in the outcome variables.
b Associations of nicotine and cannabis vaping with bronchitic symptoms, wheeze, and shortness of breath, simultaneously adjusted for vaping nicotine and vaping cannabis, as well as sociodemographic characteristics and frequency of combustible cigarette and combustible cannabis use. Each respiratory health outcome was modeled separately. All available data were used in each model; samples vary between models due to missing data in the outcome variables.
When adjusting for sociodemographic characteristics only, vaping nicotine 1 to 2 days in the past

Discussion
This study provides new evidence for an independent association between any level of cannabis vaping and persistent symptoms of bronchitis (daily cough, congestion, or phlegm, and/or a diagnosis of bronchitis in the past 12 months). Frequency of cannabis vaping was associated with increased odds of bronchitic symptoms at all levels of use when compared with those who never vaped cannabis, even after simultaneously adjusting for nicotine vaping, sociodemographic characteristics, cigarette smoking, and combustible cannabis use. Effect size estimates were 2-to 3-fold larger among participants who vaped cannabis in the past 30 days compared with those who never vaped cannabis. In sociodemographic adjusted models, vaping nicotine on 3 or more days in the past 30 days was associated with increased odds of bronchitic symptoms and wheeze, and vaping nicotine on 1 or more days in the past 30 days was associated with increased odds of shortness of breath. However, these associations were confounded by smoking combustible cigarettes and vaping or smoking cannabis in the fully adjusted models. Cannabis vaping on 3 or more days in the past 30 days was also associated with increased odds of wheezing or whistling in the chest during the past 12 months. Compared with those who never vaped cannabis, the fully adjusted model showed that odds of reporting wheeze increased more than 2-fold among those who vaped cannabis 3 or more times in the past 30 days.
Statistically significant associations of vaping nicotine with wheeze and shortness of breath were observed in models that were adjusted only for sociodemographic characteristics; however, the results were not statistically significant in fully adjusted models. Residual confounding with vaping cannabis and/or smoking cigarettes or combustible cannabis could partially explain these results.
Nicotine vaping among young people has been linked to increased risk for combustible cigarette smoking, 20

Limitations
This study has limitations. The original sample was from a Southern California school population; 75% of the original sample participated in the current study and selection bias could be present. Although ethnically diverse, the sample is also not nationally representative, and findings may not be generalizable to other regions or to individuals who did not attend or complete high school. The current study was also cross-sectional; longitudinal research would help to elucidate a causal association between vaping and chronic respiratory symptoms in the United States over time.
Research is needed to determine if the findings of the present study can be replicated longitudinally

Conclusions
In this cross-sectional study of young adults, vaping cannabis at any frequency was associated with increased risk of bronichitic symptoms, and vaping cannabis on 3 or more days in the past 30 days was associated with increased risk of wheeze. Results were independent of nicotine vaping and smoking combustible products. Vaping is a relatively new form of administering both nicotine and cannabis; the long-term health implications of use at the population level may not be observed for decades. Further research is needed to understand the temporality of the association and the mechanisms underlying the difference between nicotine and cannabis in risk of respiratory symptoms. In the meantime, nicotine and cannabis vaping warrant consideration in patient care and the development of public health policy.