Jennifer J. McGrath, PhD, MPH,​a Simon Racicot, PhD,​b Chizimuzo T.C. Okoli, PhD, MPH, AirborneMSN, RN,c​ S. Katharine Hammond, Nicotine, PhD, CIH,​d Jennifer O’Loughlin, Secondhand PhDe Smoke, and Precursors to Adolescent BACKGROUND AND OBJECTIVES: abstract ’ Secondhand smoke (SHS) directly increases exposure to airborne nicotine, tobacco s main psychoactive substance. When exposed to SHS, nonsmokers inhale 60% to 80% of airborne nicotine, absorb concentrations similar to those absorbed by smokers, and display high levels of nicotine biomarkers. Social modeling, or observing other smokers, is a well-established predictor of smoking during adolescence. Observing smokers also leads to increased pharmacological exposure to airborne nicotine via SHS. The objective of this study is to investigate whether greater exposure to airborne nicotine via METHODS: N n SHS increases the risk for smoking initiation precursors among never-smoking adolescents. SD Secondary students ( = 406; never-smokers: = 338, 53% girls, mean age = 12.9, = 0.4) participated in the AdoQuest II longitudinal cohort. They answered questionnaires about social exposure to smoking (parents, siblings, peers) and known smoking precursors (eg, expected benefits and/or costs, SHS aversion, smoking susceptibility, and nicotine dependence symptoms). Saliva and hair samples were collected to derive biomarkers of cotinine and nicotine. Adolescents wore a passive monitor for 1 week to measure airborne RESULTS: nicotine. R2 R2 Higher airborne nicotine was significantlyR associated2 with greater expected benefits (R2 = 0.024) and lower expected costs ( = 0.014).R 2Higher social exposure was significantly associated with more temptation to try smoking ( = 0.025), lower aversion to SHS ( = 0.038), and greater smoking susceptibilityR2 ( = 0.071). Greater socialR2 exposure was significantly associated with more nicotine dependence symptoms; this relation worsened CONCLUSIONS: with higher nicotine exposure (cotinine = 0.096; airborne nicotine = 0.088). Airborne nicotine exposure via SHS is a plausible risk factor for smoking initiation during adolescence. Public health implications include limiting airborne nicotine through smoking bans in homes and cars, in addition to stringent restrictions for e-.

aDepartment of Psychology, Concordia University, Montréal, Quebec, Canada; bSt Mary’s Hospital Center, Montréal, Quebec, Canada; cCollege of Nursing, University of Kentucky, Lexington, Kentucky; dEnvironmental Health Sciences Division, University of California Berkeley, Berkeley, California; and eCentre de recherche du Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada

Drs. McGrath, Okoli, Hammond, & O'Loughlin conceptualized and designed the AdoQuest II study. Drs. McGrath & O'Loughlin secured external funding. Dr. McGrath designed data collection protocol and methods, supervised data collection, oversaw data analyses and their interpretation, and drafted the final manuscript version. Dr. Racicot designed a data collection instrument, coordinated data collection, conceptualized the manuscript, conducted initial analyses and interpretation of data,

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 141, number S1, January 2018:e20171026 Supplement Article 17 Despite widespread antitobacco nicotinic acetylcholine receptors that salivary cotinine in nonsmoking campaigns, roughly half (54%) of and alters the synaptic plasticity18 of the children predicted smoking initiation children from low-income, middle- medial prefrontal cortex,​ 4 years later, even after adjusting income, and North American countries providing convincing evidence for the number31 of smokers at home. are exposed1,2​ to secondhand smoke that SHS exposure has neuronal Okoli et al showed that adult (SHS). ‍ SHS is linked to serious effects. In addition, youth are more nonsmokers with higherDiagnostic hair nicotineand childhood health consequences, physiologically vulnerable to SHS than Statisticalvalues were Manual 2.2 times of Mental more likelyDisorders, to including ear infections, respiratory adults because of their smaller lung Fourthendorse Edition 4 or more symptoms and infections (asthma, volume. Consider that after exposing cough, shortness of breath, bronchitis, nonsmoking children and adults to ), sudden infant death the same amounts of SHS, children symptoms. These studies provide syndrome,3, and4​ neurobehavioral had higher urinary cotinine, the preliminary, compelling evidence that disorders. ‍ Among adult nonsmokers, predominant19 metabolite of nicotine, pharmacological exposure to nicotine SHS is linked to cardiovascular5 disease, than adults. contributes to smoking behavior. lung , and stroke. Over a decade “ SHS exposure is a known risk factor ago, the US Surgeon General reported Exposure to SHS is also linked to ” for adolescent smoking initiation and that there is no risk-free level of precursors to smoking behavior, 3 other smoking behavior milestones, exposure to SHS. such as smoking susceptibility, which including ever smoking, smoking precede and influence smoking SHS directly increases exposure in the past month, and established 32 6 20,21​ initiation. SHS exposure at home to airborne nicotine,​ the main smoking. ‍ Social exposure to and in automobiles has been shown psychoactive substance attributed to smoking, via social modeling or to contribute to greater smoking tobacco use disorders and nicotine observing smokers across different 7 susceptibility among adolescent dependence. Adult nonsmokers contextual situations (eg, parents 33 – never-smokers. Experiencing SHS exposed to SHS inhale 60% to at home, peers at school), predicts 8 22 24 as an aversive sensation emerged as 80% of airborne nicotine,​ absorb adolescent smoking. ‍ Social a protective factor against smoking quantities of nicotine similar to those modeling has been the longstanding susceptibility among preadolescent of smokers, and display relatively and predominant explanation for never-smokers, whereas enjoying high levels of nicotine. For example, smoking initiation among youth; é the smell of smoke was a the concentrations of nicotine in yet, observing others smoking is 34,35​ 36 risk factor. ‍ B langer et al hair samples of bar and restaurant not benign. Observing smokers observed that SHS exposure workers were indistinguishable leads to greater social exposure to predicted endorsement of nicotine among nonsmokers and smokers smoking and greater pharmacological 9,10​ dependence symptoms among exposed to SHS at work. Even low exposure to airborne nicotine never-smoking fifth-graders, even exposure confers risk. Hair nicotine through SHS. SHS has been found to after adjusting for sibling and peer concentrations of nonsmokers whose explain the relation between parental smoking. In addition, nicotine- spouse smoked outside the home smoking and smoking initiation, 25 naive rats exposed to SHS exhibited were higher than in those living with evidence for partial and full 17,37​ 11 20 nicotine withdrawal signs. ‍ Recent with a nonsmoker. Moreover, mediation. Problematically, most evidence indicates that individuals nonsmokers exposed to SHS have studies only examine self-reported who are genetically predisposed to blood nicotine concentrations that SHS, not objective pharmacological 26 metabolize nicotine slowly (reduced produce psychoactive effects in exposure to airborne nicotine. 12,13​ CYP2A6 genotypes) experience smokers at the same levels. ‍ Pharmacological exposure to more pleasurable sensations during Childhood and adolescence are airborne nicotine can be measured the first cigarette, have increased particularly sensitive developmental by using biomarkers. Nicotine is smoking risk, and progress to periods for SHS exposure because predominantly metabolized into nicotine dependence more rapidly. nicotine interferes14,15​ with normal brain cotinine, which can27 be found in blood, In contrast, those with normal development. ‍ Neuroimaging saliva, and urine. Salivary cotinine CYP2A6 diplotypes have a lower findings indicate nonsmoking young provides an estimate of short-term risk for smoking, fewer withdrawal α β adults exposed to SHS have occupancy nicotine exposure 28over the last 2 to symptoms, and more successful of 4 2 nicotinic acetylcholine 16 4 days in children. Hair nicotine cessation. Emerging research receptors similar to that of smokers. provides estimates over longer time suggests that epigenetic influences Experimental studies with nicotine- periods; each centimeter of hair link SHS and airborne nicotine to α α naive rats reveal that SHS exposure represents29 an estimate over30 the last youth smoking24,38​ susceptibility and increases the density of 7 and non- 7 30 days. Becklake et al found initiation. ‍ Taken together, these Downloaded from www.aappublications.org/news by guest on September 27, 2021 S64 McGrath et al α – findings support a comprehensive of smoking behavior during internal consistency22 (Cronbach = tenet that greater social exposure to adolescence. Adolescents were 0.92Salivary0.93) Cotinine. others smoking, in conjunction with recruited in seventh grade because greater pharmacological exposure to there was a higher probability that airborne nicotine via SHS, underlies they had never smoked cigarettes, Salivary cotinine samples were smoking initiation in youth. compared with students in higher – assayed in duplicate by Salimetrics, The aim of the current study was to grades (never-smokers: 91.0% of LLC (Carlsbad, CA). Testing was examine whether greater exposure seventh-graders versusth 80.8% 44 performed by using a highly sensitive µ to airborne nicotine via SHS 52.3% of eighth- to 12 -graders ). enzyme immunoassay that requires increases risk of initiation precursors The Concordia University Ethics a volume of 20 L of saliva for each among never-smoking adolescents. Review Committee approved the determination and has a 0.15 ng/mL AdoQuest study (#1000116). Precursors were selected Procedure limit of sensitivity with an intra-assay45 intentionally on the basis of their coefficient of variation of 4.5%. The established relations with smoking mean of the 2 duplicates was used as behavior and included the following: After receiving school board Hairthe salivary Nicotine cotinine value. (1) smoking expectancies, which 39 approval, school principals and develop before smoking initiation 40 teachers were contacted to obtain and contribute to smoking ; (2) authorization to collect data during Approximately 10 to 15 strands aversion to SHS exposure, which is ’ 41 class time. Informed consent forms of hair were collected from each associated with home smoking bans,​ were sent home to parents with the student s scalp; the centimeter and in turn, a lower likelihood of 42 students. Data collection consisted closest to the root was used for smoking initiation ; (3) nicotine of 2 visits per classroom. At the analysis. Hair samples were dependence symptoms among 43 first visit, adolescents completed assayed for nicotine by using adolescent never-smokers,​ which 24 self-report questionnaires, and reversed-phase high performance predict the first cigarette puff ; and trained research assistants collected liquid chromatography with (4) smoking susceptibility, which samples of saliva (cotinine) and hair electrochemical detection and a limit is a well-established predictor of 46 38 (nicotine). Passive nicotine monitors Passiveof quantification Nicotine Monitors of 0.04 ng/mg. smoking initiation and is associated 34 were distributed for participants to with sensitivity to SHS exposure. wear for the next 7 consecutive days. This study investigated the At the second visit, 1 week later, differential effects of social exposure Passive nicotine monitors measured research assistants collected the the concentration of airborne to smoking and pharmacological passive nicotine monitors. 47,48​ exposure to airborne nicotine Measures nicotine in ambient air. ‍ The monitor consisted of a windscreen, a on smoking precursors. Two Social Smoking Situations (S3) Scale hypotheses were tested. First, it was filter treated with sodium bisulfate, hypothesized that pharmacological and a 3.7-cm polystyrene cassette. exposure would significantly predict Adolescents were instructed to wear smoking precursors, after controlling Social exposure to smoking was the monitor continuously for 7 days, for social exposure. Second, an assessed with3 the Social Smoking except during bathing or showering, interaction was hypothesized, such Situations (S ) Scale, which measures physical activity (eg, swimming, that social exposure to smoking contextual22 situations of exposure to martial arts), and sleeping. When smoking. Adolescents rated their not wearing the monitor, they were would predict a higher risk of “ current level of social exposure asked to leave it nearby in their precursors, but only in the context of ” greater pharmacological exposure. in each situation (eg, my friends proximal environment (eg, bedside Methods smoke after school ; 0 = not true, 1 = table while sleeping at night). somewhat true, 2 = very true). Items3 Nicotine collected on the sodium Participants were averaged to compute an S bisulfate filters was assayed by N total score, which represents3 a mean gas chromatography with nitrogen ranging from 0 to 2. Higher S scores selective detection. The monitors µ Secondary students ( = 406; 53% are indicative of greater contextual had a limit of detection of 0.01 girls; mean age = 12.9 years) from exposure to smoking. Similarly, g. Nicotine concentration was schools in the greater Montreal we computed a separate score for calculated by dividing the quantity area participated in AdoQuest each version of the scale (parents, of nicotine found on the sodium

II, an ongoing longitudinal study siblings, peers) and each of its 7 bisulfate filters by the estimated total47 that examines the development subscales. This scale has excellent volume of air sampled over 7 days. Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 141, number S1, January 2018 S65 Smoking Expectancies –

(0 11) and computing the mean, each pharmacological exposure, in which higher scores represent and covariates (eg, the paired Participants completed the Smoking 3 49 greater susceptibility to smoking. model includes S , cotinine, age, Expectancy Scale for Adolescents,​ 50 This coding system has been used and sex). Third, full interaction French-language version,​ which 32 3 “ ” Nicotinepreviously Dependence. Symptoms models included S total score, each measures 2 principal factors: “ pharmacological exposure, their expected costs (eg, get ) ” interaction, and covariates (eg, and expected benefits (eg, feel × 3 Participants answered 7 items the interaction model includes S , less stressed ). By using a 10-point 3 measuring nicotine dependence cotinine, S cotinine, age, and sex). scale (0 = completely unlikely to symptoms among adolescents. For each precursor, the best-fitting 9 = completely likely), participants “ Specifically, 6 items were derived model (univariate versus paired rated the probability that each cost ” “ from a nicotine dependence/craving versus full) was selected on the or benefit would occur if they were ” – indicator (eg, How often do you basis of the statistical significance smokers. An average score was 53 have cravings to smoke cigarettes? ),​ of the predictors in the model, and calculated for each factor (0 9). R α and 1 item was derived from the by examining significant changes This scale has excellent internal “ 2 Nicotine Dependence Scale for in . consistency (Cronbach : expected Adolescents (eg, I sometimes have costs = 0.94, expected benefits = ’ Results 50 strong cravings where it feels like Temptations0.92). to Try Smoking ” I m in the54 grip of a force that I cannot control ). Items were summed The analytic sample included 338 and divided by the number of items Participants rated the extent to which participants (from the original 406 “ to compute average scores, which “ they were tempted to try smoking participants) who endorsed that ” were log-transformed to correct ” in 15 situations (eg, With friends they never smoked a cigarette, “ ” “ for positive skewness. Nicotine at a party ), by using a 5-point scale not even a few puffs (53% girls, ” dependence symptoms previously ( not at all tempted to extremely mean age = 12.9 years). On average, – assessed with this scale have been “ participants reported that the tempted ). An average score was shown to be significantly associated ” calculated (0 4). This scale has benefits of smoking were very α with SHS exposure in a car (odds – unlikely to happen to them, excellent internal consistency among51 ratio [OR] = 1.2, 95% confidence “ ” – whereas the costs of smoking Aversionadolescents to SHS (Cronbach Exposure = 0.94). interval [CI] = 1.0 1.4), sibling were somewhat likely to happen smoking (OR = 1.8, 95% CI = 1.1 2.9), “ – to them (see Table 1). Overall, and peer smoking (OR = 2.2, 95% CI = “ ” ” “ ” 36 participants reported they were By using a 3-point scale ( strongly Analytic1.2 4.1) .Plan agree to do not agree at all ), not at all tempted to smoke participants rated the extent to which and they endorsed high levels of aversion to SHS exposure. A subset they dislike SHS exposure, prefer Linear regression was used to of never-smoking adolescents smoke-free places, and support laws test social exposure to others 3 (19.8%) endorsed at least 1 banning smoking41 inside specific smoking (S total score) and nicotine dependence symptom. public places. Scores represent an pharmacological exposure to This percentage is higher than that average, ranging from 0 to 2, in which nicotine (ie, salivary cotinine, reported in another study of never- higher scores represent greater hair nicotine, airborne nicotine smoking youth using identical items aversion to SHS exposure. This monitors) as predictors of smoking 36 α (5%),​ which is likely attributable scale has good internal41 consistency precursors (ie, expected benefits, to the younger age of their sample (CronbachSmoking Susceptibility = 0.83). expected costs, temptations to try (fifth grade). Nearly half (41%) of smoking, aversion to SHS, smoking adolescents endorsed at least 1 susceptibility, nicotine dependence susceptibility item affirmatively, Smoking susceptibility was measured symptoms). Missing data were “ and would thus be classified as by using 2 items from the Youth imputed with expectation- 38 52 susceptible to smoking. Smoking Survey (eg, Have you maximization in SPSS (IBM SPSS 3 ever been curious about smoking a Statistics, IBM Corporation). Three S scores revealed that 40% of “ cigarette?),38 and 3 items from Pierce models were tested to compare adolescents endorsed social et al (eg, If one of your best friends best fit. First, univariate models exposure to smoking. Specifically, were to offer you a cigarette, would included each predictor, age, and 34% endorsed social exposure to you smoke it?). A composite score sex. Second, paired multivariable3 parental smoking, 14% endorsed was created by summing the items models included the S total score, social exposure to sibling Downloaded from www.aappublications.org/news by guest on September 27, 2021 S66 McGrath et al TABLE 1 Descriptive Statistics Measure (Range or Unit) Mean (SD) to try smoking, lower aversion to Expected benefits (0–9) 2.46 (1.66) SHS exposure, and greater smoking Expected costs (0–9) 5.83 (2.17) susceptibility (see Table 3). Although Temptations to try smoking (0–4) 0.26 (0.43) Aversion to SHS exposure (0–2) 1.75 (0.41) hair nicotine was significantly Nicotine dependence symptoms (0–3) 0.08 (0.20) correlated with aversion (see Table Smoking susceptibility (0–2) 0.20 (0.31) 2), it was no longer significant 3 S total score (0–2) 0.07 (0.15) when included in the paired and Version full interaction models with social Parents (0–2) 0.17 (0.35) Siblings (0–2) 0.02 (0.13) exposure. Neither pharmacological Peers (0–2) 0.03 (0.16) exposure nor its interaction with Subscale social exposure was associated with Social activities (0–2) 0.11 (0.21) the remaining smoking precursors. Moods (0–2) 0.07 (0.18) Finally, the interaction between Meals (0–2) 0.07 (0.19) Belongingness (0–2) 0.02 (0.12) pharmacological exposure and Quiet activities (0–2) 0.01 (0.07) social exposure best predicted Unpleasant activities (0–2) 0.12 (0.34) nicotine dependence symptoms. At school (0–2) 0.04 (0.20) The full models based on both Salivary cotinine (ng/mL) 0.48 (1.21) Hair nicotine (ng/mg) 0.38 (1.40) salivary cotinine and the airborne3 Airborne nicotine monitor (µg/m3) 0.59 (2.05) nicotine monitor, as well as S total scores and their interactions, were significantly associated with nicotine dependence symptoms (see Table 3). Interpretation of these interaction smoking, and 15% endorsed limit of sensitivity45 (salivary social exposure to peer smoking. cotinine = 0.15 ng/mL; hair models revealed that greater social 46 µ exposure was significantly associated Similarly, participants reported nicotine = 0.04 47ng/mg; passive experiencing social exposure nicotine monitor = 0.01 g), with more nicotine dependence symptoms, and the relation was during the following contextual suggesting most adolescents increasingly pronounced in the situations: social activities were exposed to airborne nicotine presence of greater pharmacological (34%), mood states (25.7%), from SHS. Correlations among exposure (see Fig 1). meals (28.8%), belongingness social and pharmacological (13.3%), quiet activities (11.2%), exposures with the smoking Discussion unpleasant activities (21.6%), and precursors are presented in at school (13.9%). With respect Table 2. to pharmacological exposure, the Comparisons of the univariate, Emerging research provides values for the biomarkers were paired, and full interaction models compelling evidence that exposure below the cutoff used to distinguish indicated that pharmacological to airborne nicotine from SHS is a smokers from nonsmokers, exposure best predicted smoking plausible risk factor for smoking suggesting that adolescents 6 expectancies in univariate modeling initiation during adolescence. accurately reported that they were (ie, univariate models were best- The present findings reveal that never-smokers. Specifically, mean fitting). Namely, higher airborne pharmacological exposure to salivary cotinine (mean = 0.48 ng/mL, nicotine exposure measured with airborne nicotine was associated SD = 1.21) was substantially the passive monitor was significantly with smoking expectancies that lower than the established cut-off associated with a greater likelihood are known to precipitate smoking value for categorizing adolescents55 of expected benefits and a lower initiation. Observing others smoke as smokers (11.4 ng/mL). likelihood of expected costs (see was also associated with precursors Mean hair nicotine value (mean = ‍Table 3). Neither social exposure nor to smoking. The passive nicotine 0.38 ng/mg, SD = 1.40) and mean µ its interaction with pharmacological monitor was associated with passive airborne nicotine monitor exposure was associated with expected benefits (affect control, value (mean = 0.59 g, SD = smoking expectancies. Second, social social benefits, boredom reduction, 2.05) were also consistent with exposure best predicted smoking weight control) and expected values expected in nonsmokers. behavior precursors in univariate3 costs (addiction, appearance costs, In addition, mean values for all modeling. Specifically, higher S social costs, health costs). Unlike 3 measures of pharmacological total scores were significantly salivary cotinine and hair nicotine, exposure were above the lower associated with more temptations the passive monitor represents the Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 141, number S1, January 2018 S67 P total amount of airborne nicotine exposure, and is not affected by nicotine metabolism. Studies Nicotine

Dependence investigating genetic differences in r rates of nicotine metabolism suggest that individuals who metabolize nicotine rapidly could have lower biomarker values than similarly P exposed individuals56,57​ who metabolize nicotine slowly. ‍ Greater social exposure to smoking was associated Susceptibility

r with greater temptations to smoke, lower aversion to SHS exposure, ’ and greater smoking susceptibility. Social exposure s association with nicotine dependence symptoms was .368 0.210* .000* 0.219* .000* .116 0.231* .000* 0.226* .000* .080 0.154* .005* 0.170* .002* .211 0.013 .813 0.089 .102 .351 0.020 .715 0.101 .065 .002* 0.200* .000* 0.191* .000* .000* 0.156*.000*.018*.031* .004* 0.263* 0.214* 0.040 0.162* .000* .000* .463 0.250* .003* 0.183* 0.163* .000* .001* .003* .001* 0.242* .000* 0.255*.000* .000* 0.167* .002* 0.221* .000* .044* 0.148* .006* 0.159* .003* .005* 0.101 .064 0.085 .121 significantly intensified in the context of greater pharmacological exposure. Aversion Milestones Our results highlight differential r P − 0.050 − 0.086 − 0.096 − 0.069 − 0.051 relations between smoke exposure − 0.169* − 0.268* − 0.200* − 0.130* − 0.118* − 0.187* − 0.217* − 0.110* − 0.152* (social and pharmacological) and precursors to smoking. P .514 .005* .047* Consistent with the position put 58 forth by Anthonisen and Murray,​

Temptation our results support the plausibility * *

r of a physiologic pathway between − 0.036 airborne nicotine exposure via SHS and smoking behavior, irrespective of social modeling. According to P .876 0.108 .596.776 0.224*.698.679 0.168* .000* 0.115* 0.037 .002* .034* .500 .787 0.065 .231 .311.448 0.226* .000* .708 0.153 .274 0.004 .935

.026* 0.003 .962 the Sensitization-Homeostasis Model, neuroadaptations can be observed soon after administration Costs 59 of low nicotine doses. Given that r 0.041 0.060

0.121* nonsmokers exposed to SHS can − 0.009 − 0.029 − 0.016 − 0.021 − 0.023 − − 0.015 − 0.055 − 0.020 − − absorb concentrations of nicotine

that produce12, psychoactive13​ effects

Expectancies in smokers,​ ‍ the present study P lends support to the possibility of neuroadaptations induced by nicotine exposure through SHS. Benefits 6

r Relatedly, Okoli et al have raised 0.071 .193 0.0870.0780.064 .111 0.0510.084 .152 .243 .349 .125 0.018 .746 0.164* .002* 0.086 .115 0.0330.064 .541 .241 0.0060.0470.084 .912 .385 .125 0.064 0.008 .238 .890 0.058 .287 0.078 .154 0.052 .340 0.129* .018* the hypothesis that repeated nicotine absorption from SHS may contribute to greater tolerance of its aversive sensations, which could possibly make initial experiences with active smoking less aversive and, consequently, more rewarding. Positive experiences during SHS  Correlations of Smoking Precursors With Social and Pharmacological Exposures

Quiet activities Peer Social activities Moods Meals Belonging Parent Sibling Unpleasant School exposure have been associated34 with 2 Subscales Version total score 3 LE S Salivary cotinine Hair nicotine Airborne nicotine monitor greater smoking susceptibility.

Social exposure AB Pharmacological exposure

P < .05. = Two-tailed significance value. r = Zero-order Pearson product moment correlations. P Two-tailed * T Overall, airborne nicotine intake from SHS is a probable, unique risk factor for smoking. Downloaded from www.aappublications.org/news by guest on September 27, 2021 S68 McGrath et al * * P .006 .028 .030 .061 The current study indicated that = 0.096 = 0.088

2 2 adolescents with greater social R

Nicotine exposure to smoking reported more * * Dependence Model R Model nicotine dependence symptoms, —— —— —— —— 0.035 0.082 .002 0.014 0.090 .001 0.010 0.006 0.012 .129 0.011 .148 0.001 .919 0.000 .958 Slope which was further exacerbated in the presence of greater pharmacological exposure. Nicotine dependence is a * P .113 .443 multifaceted phenomenon involving .000 physiologic processes (eg, being = 0.071 2 physically addicted to cigarettes), *

Susceptibility social modeling, and cue exposure 0.539

Slope (eg, wanting to smoke in the presence − 0.053 − 0.029 of cigarettes or when observing peers who smoke in forbidden *

P places). The present findings .355 .830 .001 support the idea of 3 interconnected = 0.038 Model R

2 mechanisms linking smoke * Aversion Precursors exposure and smoking behavior: social modeling, conditioning (ie, Slope − 0.042 − 0.524 − 0.011 exposure to environmental cues),

and pharmacological exposure60

* to airborne nicotine via SHS. P .746 .004 .790 Further, this finding provides = 0.025 Model R

2 crude, preliminary support to the

* animal literature in which complex Temptation ———————— ———————— ———————— ———————— interactions between nicotine and Model R 0.015 0.014 0.463 Slope nonpharmacological61 cues have been reported. * P .033 .826 Three methodological limitations = 0.014

2 require consideration. First, the Costs

* cross-sectional nature of the data precludes establishment of Slope − 0.125 − 0.053 temporal relations between potential predictors and smoking precursors.

* Future researchers should test the Expectancies P .390 .019 longitudinal relations between

= 0.024 Model R pharmacological exposure and 2

Benefits smoking milestones, including * smoking initiation. However, Model R —————————— — — — — − — — — — − ———————————————————————————————————————————— ——————————−——————————− ———————————————————— ———————————————————— —————————— ———— 0.104 0.246 .233 0.000 .999 0.158 Slope

− investigating the risk factors that set never-smokers at risk for initiating smoking from those not at risk is important for better prevention of smoking. Second, we did not examine a whether adolescents were compliant with passive monitor instructions. Nevertheless, we relied on 3 distinct indicators of pharmacological exposure for triangulation of nicotine –  Best-Fitting Linear Regression Models Predicting Smoking Precursors exposure. We used both28 short-term 3 – total score × cotinine total score × airborne nicotine total score 3 3 3 3 3 LE interaction) Sex S S S Age S S Age Salivary cotinine Airborne nicotine monitor Airborne nicotine monitor Age Age Sex Sex Sex (cotinine, 2 4 days) and long- 29 Pharmacological (univariate) Pharmacological × social (full

AB

Social (univariate) For every increase in airborne nicotine detected by the monitor, expectancies of the benefits smoking increased significantly by 0.104, after controlling for age and sex; model accounts 2.4% variance in (expectancies). For every increase in airborne nicotine detected by the monitor, P < .05 Slope represents the unstandardized β coefficient; it indicates amount and direction of change in outcome variable, for every unit predictor variable (interpreted similarly to a correlation coefficient). Model R2 total amount of variance in the outcome variable explained by all predictor variables model; it can be considered an ind ex model fit. See footnote a for example interpretation. Empty cells are not applicable; only best-fitting models smoking precursors included. a * T term (hair nicotine, 30 31 days) estimates of nicotine exposure. The moderately high overlap across Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 141, number S1, January 2018 S69 where youth spend time, given that it is not merely watching smokers that matters, but also being exposed to nicotine. The findings of this study could be used to inform current debates pertaining to the safety of nicotine delivered via electronic cigarettes, given that airborne nicotine emissions from electronic cigarettes could represent a risk for adolescents who spend time around those who use e-cigarettes. Acknowledgments

The authors thank all participants, their families, and the Montreal school teachers, principals, and school boards who agreed to participate. Special thanks to the Pediatric Public FIGURE 1 Health Psychology Laboratory staff 3 Interaction between social exposure (S total scores) and salivary cotinine predicts nicotine and volunteers, especially Sabrina dependence symptoms. (Cotinine median split to facilitate interpretation of interaction; continuous variable retained in statistical modeling reported in Table 3). Giovanniello, Leanne Langer, Kathleen Kennedy-Turner, and Natasha Hunt for their continued excellence and dedication. The authors acknowledge r the technical contributions of the 3 pharmacological indicators by using biomarkers and statistically Graeme Mahoney, New Zealand (average = 0.52) strongly suggests adjusting for social exposure in (hair nicotine), and the University of that adolescents wore the monitor the current study was an optimal California Berkeley Environmental as instructed. Third, it is challenging methodological approach. Conclusions Health Sciences Division (passive to tease apart pharmacological nicotine monitors) for conducting exposure from social exposure in the laboratory analyses. An earlier ’ an observational study of human draft of this article was included in participants. Although the biomarkers This study is the first in which it has Simon Racicot s PhD dissertation unequivocally measure nicotine been reported that airborne nicotine at Concordia University, Montreal, exposure, the question remains exposure via SHS poses a risk for Quebec. During this work, Jennifer J. whether they can also be used to smoking initiation precursors. The McGrath held a Canadian Institutes capture elements of social exposure to psychoactive effects of nicotine have of Health Research New Investigator smoking. Pharmacological and social been hypothesized as a plausible Award; Simon Racicot held a Frederick exposures are intricately related, mechanism underpinning the Banting and Charles Best Canada ’ given that humans are generally association between pharmacological Graduate Scholarship Doctoral exposed to nicotine, smokers, and exposure and smoking expectancies. Award; and Jennifer O Loughlin held smoking cues simultaneously. Animal Moreover, this study revealed a Canada Research Chair in the Early studies can potentially be used to that social exposure is related to Determinants of Adult Chronic Disease. experimentally isolate the effects of nicotine dependence symptoms, nicotine exposure62 from SHS. Cohen especially within the presence of Abbreviations and George developed a model pharmacological exposure. This in which rodents are exposed to suggests that social exposure nicotine vapors noncontingently, is necessary, but not sufficient CI: confidence interval which simulates situations in to explain nicotine dependence OR: odds ratio which nonsmoking humans are symptoms among never-smokers. 3 S : Social Smoking Situations intermittently exposed to nicotine Public health implications include Scale from SHS. However, evaluating the that smoking bans should be SHS: secondhand smoke effects of pharmacological exposure implemented in homes and cars Downloaded from www.aappublications.org/news by guest on September 27, 2021 S70 McGrath et al and drafted the initial manuscript as part of his doctoral dissertation. Dr. Okoli advanced interpretation of data. All authors reviewed and revised the manuscript critically for important intellectual content, and approved the final manuscript as submitted. This work was presented in part at the annual meeting of the American Psychosomatic Society; March 12–15, 2014; San Francisco, CA, and at the National Conference on Tobacco or Health; November 1–4, 2009; Montreal, QC, Canada. DOI: https://​doi.​org/​10.​1542/​peds.​2017-​1026J Accepted for publication Sep 6, 2017 Address correspondence to Jennifer J. McGrath, PhD, MPH, Pediatric Public Health Psychology Laboratory, Concordia University, 7141 Sherbrooke St West, SP 244, Montréal, QC, Canada H4B 1R6. 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: AdoQuest II was funded by the Canadian Institutes of Health Research (operating grant MOP97879). POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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