Smoking, e-cigarettes and the effect on respiratory symptoms among a population sample of youth: retrospective study.

Introduction E-cigarettes have been steadily increasing in popularity, both as cessation methods for smoking and for recreational and social reasons. This increase in vaping may pose cardiovascular and respiratory risks. We aimed to assess respiratory symptoms in youth users of e-cigarettes and cigarettes. Methods A cross-sectional survey design was utilized to assess Canadian youth aged 16-25 years old. Participants were recruited from the Ontario Tobacco Research Unit Youth and Young Adult Research Registration Panel November 2020 to March 2021. A total of 3,082 subjects completed the baseline survey. Of these, 2660 individuals who did not have asthma were included in the analysis. The exposure of interest was vaping dose, pack equivalent years, equivalent to cigarette pack years incorporating number of puffs per day, number of days vaped per month, and number of years vaped. Respiratory symptoms were measured using the five-item Canadian Lung Health Test. Poisson regression analyses were performed while adjusting for demographic confounders, stratified by smoking status. A non-stratified model tested the interaction of status and vaping dose and the effect of vaping device used was assessed among ever vapers. Analyses controlled for demographic characteristics, use of cannabis and alcohol, and survey date. Results Each additional puff year increased the rate ratio of respiratory symptoms by a factor of 11.36 (95%CI: 4.61-28.00; p<0.001) for never smokers, but among current daily smokers higher pack equivalent years were not associated with more respiratory symptoms (0.83; 95% CI: 0.23., 3.11). Among current vapers, those using pod-style devices were more likely to have more respiratory symptoms (1.25; 95% CI: 1.08, 1.45) after adjusting for dose. Conclusions Vaping is associated with an increased risk of reporting respiratory symptoms among never smoking youth and non-daily ever cigarette smokers. Use of e-cigarettes among non-smokers should be discouraged.


Introduction
76 Cigarette smoking has long been known to be associated with poor respiratory health outcomes, 77 including lung cancer, chronic obstructive pulmonary disease (COPD), and severe asthma. 1 In 78 the past several decades, the prevalence of cigarette smoking has decreased drastically across 79 North America. Even so, it remains prevalent with an estimated 14.8% of Canadians smoking 80 cigarettes in 2019, which is slightly higher than rates of 14.1% in the United Kingdom and 81 14.0% in the United States. 2, 3,4 82 While the use of cigarettes has become less common, electronic cigarettes (e-cigarettes) have 83 quickly gained global popularity as both smoking cessation aids as well as recreational nicotine 84 delivery devices. 5 This rise in use has been especially prominent amongst youth, with several 85 studies observing large increases in the prevalence of youth e-cigarette use in both the United 86 States and Canada within the past decade, with 15% of youth in Canada aged 15 to 19 reporting 87 past 30-day use of e-cigarettes in 2019, compared to only 6% in 2017. 6,7,8 Despite being initially 88 introduced as a supposedly safer alternative to cigarettes, e-cigarettes have been found to be 89 associated with some health-related harms similar to cigarettes. 9,10 Further, the use of e-cigarettes 90 has been associated with additional harms unique to the electronic devices. 10 Literature 91 surrounding the health impacts of e-cigarette use is still evolving, but existing research has 92 identified both short-and long-term respiratory harms due to e-cigarette use. 11 However, existing 93 research primarily includes adult samples, limiting generalizability to youth populations, which 94 differ biologically, psychologically, and sociologically. Further research is thus necessary to 95 assess the effect of vaping frequency on risk of respiratory symptoms, especially among youth 96 who are at highest risk of vaping initiation. Additionally, the association between vaping device 97 type/e-cigarette liquid flavour and respiratory symptoms must be assessed as different devices . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03. 10.22272186 doi: medRxiv preprint 98 provide varying doses of vapor per puff, which may impact risk of respiratory symptoms among 99 users of certain device types, even with a lower vaping frequency.
100 In addition, many individuals engage in dual use of cigarettes and e-cigarettes. 12,13 Motivations 101 for dual use vary, with research suggesting that individuals who initiate the use of e-cigarettes 102 with the goal of smoking cessation are more likely to engage in dual use than to engage in e-103 cigarette use alone. 12 This may be the case because smokers who use e-cigarettes as smoking 104 cessation aids may not fully transition from smoking to vaping, despite often beginning with the 105 intention to quit smoking entirely. 12 106 Research surrounding the health impacts of the dual use of cigarettes and e-cigarettes remains 107 limited. Results from existing studies have been mixed, with some finding that dual use leads to 108 mitigated health-related harms due to the overall decrease in the use of cigarettes. 12,13 Other 109 research has found that the potential mitigation of health-related harms as a result of switching 110 from cigarettes to e-cigarettes are negated in those who continue to smoke cigarettes alongside 111 using e-cigarettes. This may be observed as no difference in health-related harms between dual 112 users and single product users or increased harms among dual users. Notably, most of these 113 studies focus on the health-related impacts of either smoking or vaping, but not both. [14][15][16][17][18] Finally, 114 much research remains inconclusive surrounding the harms associated with the dual use of 115 cigarettes and e-cigarettes, as well as with regards to how these impacts differ between 116 individuals who are solely users of either cigarettes or e-cigarettes. 12 117 The current analysis sought to use survey data to understand better the association between e-118 cigarette use and self-reported respiratory symptoms among youth, along with the association 119 between self-reported respiratory symptoms and e-cig dose (number of puffs per month), vaping 120 device, e-cigarette liquid flavour, and years vaped. In doing so, we seek to add to a growing body . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 121 of research regarding the extent of harms related to the use of e-cigarettes. Additionally, the 122 study aims to assess the interaction associated with the dual use of cigarettes and e-cigarettes on 123 respiratory symptoms. Based on current research on both vaping and smoking cigarettes, we 124 hypothesized that individuals who smoked cigarettes regularly and those who vaped regularly 125 would report more respiratory symptoms compared to non-smokers and non-vapers. We further 126 hypothesized that dual use of cigarettes and e-cigarettes would be associated with more 127 respiratory symptoms compared to vaping alone, but lower compared to cigarette smoking alone, 128 due to satiation of cravings that would decrease cigarettes smoked daily. However, this 129 assumption of decreased cigarette intake may be incorrect, as some studies reported lower levels 130 of smoking in dual users, while others reported no notable change in number of cigarettes 131 smoked, though fewer respiratory symptoms were still observed. 18 To further this understanding, 132 we also considered potential confounding factors in the relationship between smoking and 133 respiratory health, including age, sex, education level, and other substance use.  . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 144 and age (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Participation rate was 60%. Younger females, those with higher 145 education, and those who had never used e-cigarettes or cigarettes were more likely to 157 The outcome variable was the self-reported occurrence of adverse respiratory symptoms. Data on 158 five respiratory symptoms were collected, with survey respondents identifying any symptoms 159 they experienced in the past four months (yes/no). The five symptoms were coughing regularly, 160 coughing up phlegm regularly, feeling out of breath from even simple chores, wheezing when 161 exerting oneself (e.g., through exercise or going up the stairs), and getting many colds 162 (specifically those that take longer to recover). The five questions were combined to form an 163 overall respiratory symptoms variable, the Canadian Lung Health Test. This measure was 164 originally validated for use in screening for COPD but comprises a set of questions routinely 165 used by clinicians to evaluate patients for respiratory disorders. 19 The maximum number of . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 166 respiratory symptoms that could be selected by a respondent was five and the minimum number 167 of symptoms was zero.
168 Cigarette status was self reported and categorized into (never smoked a cigarette, smoked a 169 cigarette but not a current daily smoker, and daily smoker). Participants also reported number of 170 cigarettes smoked per day, and whether or not they were past month users of alcohol and 171 cannabis. Participants were asked what vaping device they had last used, and how long they had 172 been vaping at the time of survey completion. Data on demographic characteristics were also 173 collected (sex, age, education, parental status, marital status, province of residence, and race).
174 Participants also reported whether or not they had received a diagnosis of asthma. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 211 symptoms the majority of participants did not report experiencing the symptom, regardless of . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 212 smoking or vaping status, the majority of daily smokers, regardless of vaping status, did report 213 coughing regularly in the last four months (65.6% of daily smokers, non-vapers; 57.1% of daily 214 smokers, daily vapers), and the majority of daily smokers, non-vapers reported coughing up 215 phlegm regularly (52.2%). Additionally, daily smokers, daily vapers, and daily dual-users were 216 all more likely to report experiencing any of the five symptoms compared to non-daily or never-217 users of either cigarettes or e-cigarettes. Daily smokers were also more likely to report 254 With regards to dual use, however, we observed that those individuals who vaped daily and 255 smoked cigarettes daily did not demonstrate additional risk from vaping. That is, dual users 256 reported notably high levels of respiratory symptoms compared to non-users of both cigarettes 257 and e-cigarettes, though an increase in e-cigarette puffs resulted in a marginal decrease in rate of . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 258 respiratory symptoms. These results are congruent with existing studies that reported health 259 benefits of dual use compared to exclusive cigarette smoking. 12,13,15,17 However, due to the high 260 baseline of respiratory symptoms among cigarette smokers, it is difficult to ascertain the true 261 benefit of dual-use without longitudinally monitoring changes in smoking behaviours of 262 exclusive smokers that become dual users, to determine the mechanism behind this decrease in 263 symptoms. 295 This study documented a potential correlation between vaping and an increase in respiratory 296 symptoms. A secondary finding was an interaction between dual use of cigarettes and e-297 cigarettes and a decreased risk of respiratory symptoms compared to cigarette smoking alone, 298 which exhibited a higher baseline of symptoms. Further longitudinal research using physical 299 health assessments and biomarkers is necessary to explore this association further. 300 301 Acknowledgements 302 Dr. Eissenberg is a paid consultant in litigation against the tobacco industry and also the 303 electronic cigarette industry and is named on one patent for a device that measures the puffing 304 behavior of electronic cigarette users and on another patent for a smartphone app that determines 305 electronic cigarette device and liquid characteristics. Other authors have no disclosures to report. 306 The CSTP is supported by grant number U54DA036105 from the National Institute on Drug 307 Abuse of the National Institutes of Health and the Center for Tobacco Products of the U.S. Food . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint 308 and Drug Administration. The content of this message is solely the responsibility of the author 309 and does not necessarily represent the views of the NIH or the FDA The cohort study was funded 310 by CIHR. The funding sources had no role in the study design, collection, analysis, and 311 interpretation of data, writing the report and the decision to submit the report for publication.
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The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint Tables   Table 1. Demographics for all variables included in the multivariable linear regression model . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted March 13, 2022 Table 1). * p<0.05, ** p<0.01, *** p<0.001 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.10.22272186 doi: medRxiv preprint