Young Adult EC Use and Respiratory Outcomes
Conditions: E Cig Use
Sponsor: Ohio State University Comprehensive Cancer Center

 
NCT04395274 
 
05/03/2024 
 
 
 
“Young Adult EC Use and Respiratory Outcomes (K01)” 
 
 
 
 
 
 
 

 
  
2 
 
Table of Contents 
I. 
Objectives 
2 
II. 
Background and Rationale 3 
III. 
Procedures 
5 
A. 
Research Design 5 
B. 
Sample 5 
C. 
Measurement / Instrumentation: 6 
D. 
Detailed Study Procedures 7 
E. 
Internal Validity 
12 
 
F. 
Data Analysis  
13 
IV. Bibliography  
14 
V. 
Appendix A 
 
19 
 
 
 
 
 
 
 
 
 
 
 
 
 
I. 
Objectives  
Nearly 1 in 5 U.S. high school students reported current use of any tobacco product in 2017. Tobacco use is 
often started and established during adolescence,15,16 with 90% of smokers starting before the age of 18.15,16 
Electronic cigarettes (ECs) remain the most commonly used tobacco product among young adults,15-20 with new 
“pod mod” style devices, like JUUL, further driving up prevalence.21-24 Studies in adults indicate that EC use is 
associated with decreased airway reactivity and inflammation, but no research has examined the effects of EC 
use on respiratory health in youth. Objective indicators of respiratory health (airway reactivity and inflammation) 
and pulmonary functioning are known predictors of lung disease (e.g., asthma25,26, COPD25,27-29). As such, 
prospective longitudinal research examining the impact of EC use on these indicators is vital to 
understanding the potential health consequences of EC use among young people. 
  
While national longitudinal studies, like the Population Assessment of Health and Tobacco (PATH), aim to 
capture tobacco initiation, perceptions, and patterns of use, it has several limitations. First, PATH does not 

 
  
3 
 
include objective measures of pulmonary functioning and respiratory health (e.g., airway reactivity and 
inflammation)—even though these factors are identified as an understudied and priority area of investigation 
by the American Thoracic Society (ATS)30 and FDA31. Second, PATH requires young adults to retrospectively 
report on tobacco use behaviors and does not link these behaviors to respiratory outcomes. The present 
study will leverage multimethod approaches including biological and naturalistic measures (EMA) to innovatively 
capture pulmonary functioning and respiratory health prospectively among sample of young adult exclusive-EC 
users (n = 100) and never-users (n = 50) ages 18 – 25 years old. By collecting more granular detail of daily EC 
use patterns (e.g., frequency, quantity) and corresponding daily measures of pulmonary health, we will be able 
to more clearly determine the role of daily within-person fluctuations in frequency/quantity of EC use and its links 
to pulmonary functioning. Moreover, as cross-sectional surveys show that 54% of young tobacco users dual use 
ECs with OTP, we will also collect EMAs on experimentation with and co-use of other tobacco products 
(OTPs).32,33 This data will provide an additional opportunity to examine the respiratory and pulmonary impact of 
dual and polytobacco use on respiratory health and pulmonary functioning among young adults.  
 
The proposed study will address the current knowledge gap using a prospective, 1-year, longitudinal 
design combined with five intensive 2-week “measurement bursts” of EMA and multiple measurements 
of respiratory functioning. To examine the association between frequency of use (e.g., number of vaping 
sessions per day, frequency of days used), self-reported nicotine dependence, respiratory health, and biological 
markers of respiratory inflammation, complementary 2-week EMA and home-based spirometry (2/day, morning 
and night) assessments prior to laboratory visits will provide a more accurate estimation of young adults tobacco 
use as it occurs in, or near “real time” in the natural environment and the subsequent impact this has on acute 
reductions in pulmonary functioning. If never-users become users, we will incorporate relevant data into the user 
group at the visit during which they first report tobacco or EC use.    
 
Aim 1: To compare longitudinal changes (over the 1-year monitoring period) in pulmonary functioning 
and respiratory health between exclusive-EC users and healthy controls in repeated sessions. H1a: 
Exclusive-EC users will have significantly lower levels of respiratory and pulmonary functioning (e.g., increase 
in inflammation markers (e.g., IL-6, IL-8); decreased forced expiratory volume (FEV1), forced vital capacity 
(FVC), FEV1/FVC ratio). H1b: Among exclusive EC users, greater frequency of use (number of vaping sessions 
per day, number of days used) and increased nicotine dependence (significant increases in dependence scores 
over 1 year) will be associated with decreased respiratory and pulmonary functioning. 
Aim 2: To identify a dose-response relationship between quantity / frequency of EC use (daily EMA 
monitoring) and acute changes in pulmonary functioning (same-day, home-based spirometry). H2a: EC-
exclusive users who report multiple vape sessions per day and spend more time vaping will show acute 
decreases in pulmonary functioning. H2b: Among all participants, use of ECs in combination with combustible 
OTP will be associated with decreased pulmonary functioning.  
Exploratory Aim 3: To identify the impact of EC+OTP use on respiratory and pulmonary health. H3a: Dual 
users of EC+OTP will have decreased respiratory and pulmonary functioning compared to EC-exclusive and 
Never-tobacco users. We will examine how user status impacts acute (EMA/spirometry) and longitudinal 
changes in respiratory health (baseline to 12-month visit).   
 
Understanding the respiratory health effects of e-cigarette use among young adults has implications for the 
development of tobacco use prevention campaigns and for the regulation of ECs by the FDA.  
 
II. 
Background and Rationale  
Public health efforts have been effective in reducing young adults use of cigarettes, and rates of cigarette use 
are the lowest ever recorded;34 however, young adults use of ECs have rapidly increased and this may be 
changing how young adults engage with OTPs.21-23,32,35,36 In 2017, an estimated 3 million youth (20%) reported 
current use of any tobacco product, and of those, 1.4 million reported current use of ≥2 tobacco products,32 with 
a higher prevalence of use among males than females. Among youth and young adults, ECs continue to be 
the most commonly used tobacco product (11% of current users), followed by cigarettes (8%), cigars (8%), 
smokeless tobacco (6%), and hookahs (5%).32,37 Moreover, the latest findings from the 2018 National Youth 
Tobacco Survey show a 75% increase in EC use among high school students between 2017 and 2018.36 A 
handful of prospective survey studies suggest that EC use is associated with greater risk for subsequent cigarette 

 
  
4 
 
smoking and OTP use.33,38 As such, public health officials and regulators are concerned that increased use of 
EC may lead to increased nicotine dependence and escalation of harmful tobacco product use.   
 
Adolescence and young adulthood is a critical time in which tobacco product experimentation occurs, and recent 
studies highlight that EC experimentation has been shown to predict the initiation of combustible cigarette 
smoking and OTP use during this developmental period.33,39-42 Data suggest EC use is less stable among young 
people), with significantly more transitions between various tobacco products.43-45 This is concerning as multiple 
tobacco product use increases nicotine exposure46-48 and may also increase nicotine dependence.46-48 Nicotine 
is a highly addictive stimulant and dependence can be acquired even at low levels and prior to the initiation of 
daily use.49-51 Thus, such fluctuations in young adults may be critical to the development of long term 
dependence. The biological consequences of nicotine dependence may be particularly harmful for young adults 
given the rapid changes in brain development during this time period.16  
 
While the harmful pulmonary effects of combustible tobacco use are well documented, including COPD25,27-29 
and the development and exacerbation of asthma,9,10,2527,52,53 very little is known about the respiratory effects of 
EC use. EC aerosol contains several chemical constituents such as diacetyl or benzaldehyde, known to affect 
the respiratory system.54-59 To date, only a handful of studies have examined the respiratory effects of ECs in 
humans,60-65 and none have focused on acute or longitudinal effects in young adults. These studies suggest that 
EC use has a significant impact on pulmonary and respiratory functioning.60-66 Specifically, among adults, use of 
an EC for just 5 minutes increases airflow resistance,64 decreases oxidative stress,64,67 and increases particle 
deposition within the lungs – even more than cigarettes.67 After 15 minutes of EC use, one study identified 
decreased cough sensitivity, but found full recovery within 24 hours of non-use.68 Further, adult EC puff 
topography studies indicate that the average EC user inhales a significant volume of e-liquid aerosols,69 which 
exposes the entire respiratory epithelium to substantial concentrations of fine particulate matter.69 This is 
concerning as particulate matter can travel deeply into the respiratory tract into the lungs and cause health 
effects (e.g., decreased lung function, worsen medical conditions such as asthma and heart disease) upon 
inhalation.69,70 Adult studies examining EC puff topography indicate that EC users’ puff duration lasts significantly 
longer than a typical cigarette smokers’ puff71,72 (2.7-3.5 seconds73,74 vs. 2.3 seconds72) and EC users have 
similar flow rates (about 37 ml/s).74,75 This may potentially expose users to more chemical constituents (e.g., 
diacetyl or benzaldehyde54-59) and decrease pulmonary functioning and overall respiratory health.58,76 These 
studies indicate that the respiratory physiologic effects of EC use, even after short-term use, are similar to some 
of the effects seen with tobacco smoking;54-59,64,71,72,77 however, the long-term health effects of EC use are 
unknown, potentially adverse, and worthy of further investigation. Further, the current young adults literature is 
limited to respiratory effects derived from self-report10,60,61 and cross-sectional7,10,60 data. These data indicate a 
correlation between young adults EC use and chronic bronchitic symptoms60 and increased cough or phlegm.61 
Currently, no studies have objectively measured changes in respiratory health in adolescents as they relate to 
EC use, specifically, the impact of EC puff topography and frequency of use on respiratory and pulmonary 
functioning.  
 
This study uses complementary methods of data collection (self-report, biological samples, and EMA) to address 
several gaps and limitations in the extant literature. First, data from this study will complement current national 
longitudinal studies, like the Population Assessment of Health and Tobacco (PATH), National Youth Tobacco 
Survey (NYTS), National Survey on Drug Use and Health (NSDUH). While data from PATH, NYTS, and NSDUH 
capture youth tobacco initiation, perceptions, and patterns of use, they do not include objective measures of 
pulmonary functioning and respiratory health (e.g., airway reactivity and inflammation); important indicators for 
the development of asthma and COPD. The present study addresses this knowledge gap by providing a 
comprehensive assessment regarding the acute and longitudinal respiratory effects of young adults EC 
use. In the present proposal, each assessment (baseline, 3-, 6-, 9-, and 12-months) will employ a battery of well-
validated, objective respiratory evaluations to examine how EC use is acutely related to respiratory inflammation 
and pulmonary functioning. Second, PATH, NYTS, and NSDUH require young adults to retrospectively report 
on tobacco use behaviors and do not link these behaviors to respiratory outcomes; outcomes that are correlated 
with tobacco-related health effects in older adulthood. The present study will incorporate ecological 
momentary assessment (EMA) which will provide a more accurate estimation of the impact of EC use, 
measured in, or near “real time” and in the natural environment on pulmonary functioning. In addition 

 
  
5 
 
to spirometry, this study will also incorporate secondary assessments of airway inflammation measured 
via nasal epithelial lining fluid (NELF) samples. If pulmonary functioning and respiratory health is found to be 
worse over time among young adults who use ECs compared to young adults who do not, this provides further 
evidence that ECs negatively impact public health and should be regulated more stringently by FDA. Additionally, 
the use of in-home and laboratory measures will provide more granular detail about how different EC use 
patterns (e.g., frequency, quantity) influence pulmonary health. While the PATH, NYTS, and NSDUH provide 
informative data regarding tobacco experimentation and initiation, perceptions of harm, and patterns of use, the 
retrospective nature requires young adults to report on behaviors over the previous year. We will also utilize 
EMA to obtain information about the experimentation with OTPs and elucidate the contextual factors associated 
with these behaviors. Finally, cross-sectional surveys estimate that among youth and young adult tobacco users, 
42% use ECs exclusively 32, while 54% dual use ECs with OTPs.32,33 This is particularly concerning as 
combustible tobacco use frequently leads to poor respiratory health, including smoking-related illness like 
COPD25,27-29,78 and asthma.25,27,53 The present study will identify not only when experimentation and co-
use of OTPs occurs, but the impact of EC+OTP use on subsequent respiratory and pulmonary health. 
These data will provide a series of acute and longitudinal objective indicators of respiratory health and associated 
EC use, which is urgently needed to advocate for more effective regulations on ECs to reduce young adults use.  
 
In summary,  adolescence and young adulthood is a critical time for tobacco product experimentation, the 
escalation of tobacco use, and dependence. ECs are currently the most used tobacco product among youth 
and young adults, yet very little is known about what impact they may have on respiratory health. The proposed 
study will address this knowledge gap using a prospective, 1-year, longitudinal design combined with five 
intensive 2-week “measurement bursts“ of EMA, spirometry, and nasal epithelial lining fluid (NELF) samples to 
assess respiratory health and inflammation. The longitudinal design will provide (a) an assessment of changes 
in patterns of EC and other tobacco use over time, and (b) the influence of daily EC quantity/frequency, type of 
EC liquid used, and dual use with OTPs impact on respiratory health among young adults.   
 
Preliminary Studies. Dr. Tackett completed a NIH F32 (F32HL138734) study, which incorporates secondary 
data analyses from the PATH study, qualitative interviews assessing why and how youth with asthma obtain and 
use ECs. Initial examination of study objectives indicate that youth with asthma are more likely to use ECs and 
OTPs than their healthy peers, which is consistent with the current literature.9,10 While this study will provide 
preliminary evidence, from a relatively small sample (N = 60) regarding the acute health effects of, and reasoning 
behind youth EC use, it may only be generalizable to youth with asthma (8% of the US population of youth) and 
not to the larger population of youth who experiment with or use ECs  (15-20% of the US population of youth). 
Further, youth with asthma already have impaired respiratory and pulmonary functioning, and thus our use of 
cross-sectional indicators of pulmonary health may be attributable to normative changes or nonadherence to 
asthma medications/poor disease management. By building on these initial findings to (1) provide a more 
complete assessment of EC use, (2) a more comprehensive, advanced, and longitudinal assessment of 
respiratory/pulmonary functioning, and (3) utilizing a “healthy” control group (i.e., referred to as “never users”), 
we can elucidate if changes in respiratory health are associated with EC use, rather than a confound of asthma 
status. 
 
III. 
Procedures 
 
A. Research Design.  
 
Overview: Figure 1 (below) depicts the participant study flow. Using a 1-year, prospective longitudinal design, 
150 young adults (100 exclusive-EC users; 50 never-users) will complete 5 study visits (baseline, 3-, 6-, 9-, and 
12-months), which will include collection of nasal epithelial lining fluid (NELF) samples to examine objective 
respiratory outcomes and exposure/use of nicotine (i.e., cotinine). To assess acute changes in pulmonary 
functioning related to tobacco product use, participants will complete twice daily EMA and home-based 
spirometry for the 2-weeks prior to each follow-up study session visit. Exclusive-EC users’ will provide self-
reported data on frequency, quantity, and number of days ECs were used to examine the association between 
frequency and quantity of EC use and self-reported nicotine dependence and respiratory health. 

 
  
6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
B. Sample 
 
Participant Screening and Enrollment:  
Given that EC use is more common during high school and young adulthood,32-34,38,40,42,57,60,79,80 we will recruit a 
total of 100 exclusive-EC users and 50 never-users, ages 18-25. Participants will be recruited from the general 
community via targeted internet advertisements (i.e., Facebook, Instagram, and Twitter). Consistent with current 
protocols, interested participants will be screened over the telephone or in-person. Participants who meet the 
following eligibility criteria will be asked to take part in the study.  
 
Inclusion criteria: 1) own a smartphone and willing to add study EMA and iSpirometry application to it; 2) a current 
exclusive-EC user (endorse ≥weekly use over the past 3 months) and not currently using other tobacco products; 
3) between the ages of 18-25 years old at the time of enrollment; 4) willing to provide informed consent, 5) willing 
to complete five, 2-week periods of twice daily EMA and home-based spirometry, 5) read and speak English; 
and 6) never-users must indicate never trying any tobacco product to be eligible for enrollment.11,82  
 
Exclusion criteria: 1) self-reported diagnosis of lung disease including cystic fibrosis or chronic obstructive 
pulmonary disease; we will not exclude youth who have asthma, but will incorporate this as a covariate during 
analyses; 2) unstable or significant psychiatric conditions (past and stable conditions will be allowed); 3) history 
of cardiac event or distress within the past 3 months; 4) are currently pregnant, planning to become pregnant, 
or breastfeeding (will be verified with urine pregnancy test); and 5) are blind, severely visually impaired, deaf, 
hard of hearing, or have a severe motor disability. If the participant is eligible then they will be invited to meet 
with the trained study RA to review study procedures and obtain informed consent. These procedures have been 
successfully implemented in previous protocols with our study team. Upon completion of this study, we will 
provide participants with access to free tobacco dependence resources via the Tobacco Quit line (e.g., 1-800-
QUIT-NOW). If participants ask for smoking cessation resources or indicate they would like to quit, we will 
immediately provide these resources to participants (see protection of human subjects for more detailed 
information). 
 
Recruitment Feasibility and Retention. We will recruit our sample from a combination of resources, including 
online advertisements, and the databases of past participants. After a brief phone interview, eligible participants 
will join a video conferencing session (e.g., zoom, teams) where research staff will briefly explain the study, 
ensure inclusions/exclusion criteria, review and sign the informed consent, and enroll the participant.  
 
Retention: Participants will receive the following compensation for taking part in this study: $25 for completing 
both the Baseline and Day 1 Visits, if the participant is eligible for the study ($25 total) $25 each for completing 
Figure 1. Participant Study Visit Flow Chart 

 
  
7 
 
the 3 Month, 6 Month, 9 Month, and 12 Month Visits (a maximum of $100) $5 for collect of NEFL sample at Day 
1, 3 Month, 6 Month, 9 Month, and 12 Month Visits (a maximum of $25 total) $1 for completing each daily survey 
and $1 for completing each spirometry blow(a maximum of $280) $50 bonus for completing 75% or more (at 
least 105 total) of the daily surveys and attend at least 3 of the 5 remote study visits Participants who are eligible 
for the study can receive a maximum of $480 for participating. Participants who are determined ineligible during 
the consent process or at baseline for the study will receive $10 compensation for their time. We will also facilitate 
retention by: 1) obtaining multiple sources of contact; 2) offering evening/weekend appointments, and 3) provide 
reminder calls/texts/emails. The study app that will be added to each participant’s phone will also send reminders 
of upcoming appointments and to complete EMAs.  
 
C. Measurement / Instrumentation:  
 
Questionnaire data will be collected via the MyCap app or over the phone by a research assistant using REDCap. 
See Table 2 for timing of measures. Pregnancy exclusion will be confirmed with a urine test. Exclusive-EC users 
and never-users will both complete objective measurements of respiratory health and self-report measurements 
of nicotine dependence.51 Spirometry will be conducted in a standing position and according to the 
recommendations of ATS clinical Guidelines.84 Forced expiratory volume (FEV1), forced vital capacity (FVC), 
and FEV1/FVC will be measured. Nasal epithelial lining fluid (NELF) samples will provide objective data on 
respiratory health (e.g., markers of inflammation, host defense, and lung injury) and will provide estimates of 
nicotine exposure/use viacotinine (i.e., the predominate metabolite of nicotine) will also be examined to provide 
objective indicators of recency of EC and/or OTP use. Participants will also complete a battery of self-reported 
questionnaires at each study session asking about demographic characteristics, nicotine dependence, 
frequency/quantity of EC use, perceptions of harm, and secondhand exposure to other tobacco products. Drug 
Effects Questionnaire (DEQ).45 A modified version of the DEQ will be used to rate EC appeal on visual analog 
scales (range, 0 “not at all” – 100 “extremely”). Items assess liking/wanting (the average of “I feel good EC 
effects,” “I feel the EC strength,” and “I like the EC effect”). EC Wisconsin Inventory of Smoking Dependence 
Motives (e-WISDM).78,79 The EC Wisconsin Inventory of Smoking Dependence Motives (e-WISDM) is a 37-item 
questionnaire that includes 11 subscales and two overarching subscales: Primary Dependence Motives (PDM) 
and Secondary Dependence Motives (SDM). Minnesota Nicotine Withdrawal Scale (MNWS).79 Nicotine 
withdrawal will be assessed using the empirically validated 15-item version of the Minnesota Nicotine Withdrawal 
Scale. 
This 
measure 
assesses 
smoking 
craving, 
anger/irritability, 
anxiety, 
depressed 
mood, 
restlessness/difficulty concentrating, increased appetite, sleep problems, and somatic symptoms (nausea, 
constipation, sore throat, dizziness, coughing) rated on a scale of 0 (none/not at all) – 4 (severe/extremely).  
 
Real-Time Assessment Procedures. Ecological Momentary Assessment (EMA): All participants will complete 
twice-daily EMA monitoring “bursts” for the 2-weeks prior to each scheduled laboratory visit (see Table 2 for 
specific EMA measures). Participants will receive prompts delivered to their phone in the morning and evening, 
corresponding to their sleep/wake cycle (assessed at baseline). Consistent with our team’s previous studies, 
EMA surveys will assess current mood, nicotine craving, nicotine withdrawal symptoms, stress, recency of 
vaping/OTP use, current setting, frequency and quantity of EC and/or OTP use (since the previous assessment), 
flavors, nicotine concentration, EC device used, and satisfaction and pleasure from about their most recent EC 
use. The participants phone will audibly and visually cue EMA prompts lasting for 30 seconds. If the participant 
has not responded after 5 prompts (5 minutes apart), the assessment will be recorded as missed. Based on the 
experience Dr. Tackett’s prior experience, EMA assessments take <5 minutes to complete. All EMA 
assessments will be date and time stamped for future analyses. Immediately after each EMA survey, participants 
will also complete handheld spirometry assessments (Figure 2, above). Participants will be prompted to complete 
spirometry assessments each day following completion of the EMA. Step-by-step directions to complete the 
spirometry test will be provided. The test is simple, easy to use, and provides a complete pulmonary function 
test in < 2 minutes. The EMA and iSpirometry applications will include a video to show participants how to 
complete the test, if additional support is needed. Results of these tests include peak flow and FEV1/FVC (Figure 
2). All spirometry data are date and time stamped and saved within the application to a secure server. For the 
use of this study, participants will not receive feedback on spirometry test results.    

 
  
8 
 
 
  
TABLE 2. ASSESSMENT OVERVIEW AND OUTCOME MEASURES.   
  
  
Five Virtual “Laboratory” 
Sessions
 
 
EMA Measures 
BACKGROUND 
MEASURES
Baseline
3-
month
6-
month
9-
month
12-
month
Baseline
Month 
2
Month 
5
Month 
8
Month 
11
Sociodemographic 
Measures  
 
 
 
 
 
 
• 
EC exclusive and OTP use  
- 
EC/OTP product used  
- 
Flavor used  
- 
Nicotine Concentration  
• 
Drug effects/liking  
• 
Handheld Spirometry  
• 
Affect/mood/stress  
• 
Minnesota Nicotine Withdrawal 
Scale  
• 
Hooked on Nicotine Checklist  
• 
Recency of product use  
• 
Social setting/location  
• 
Product experimentation (OTP 
and EC use)  
RESPIRATORY AND PULMONARY HEALTH 
MEASURES  
 
 
Spirometry  





NELF Biosample 
Collection 
(measures 
respiratory 
markers 
and 
cotinine) 
 
 
 
 
 
 
Urine 
pregnancy 
tests 
 
 
 
 
 
 
NICOTINE DEPENDENCE/ABUSE LIABILITY 
 
 
Drug 
Effects/Liking 
Questionnaire  
 
 
 
 
 
 
 
Minnesota 
Nicotine 
Withdrawal Scale 
(MNWS) 
 
 
 
 
 
 
Product Use and 
Dependence 
(Hooked on 
Nicotine Checklist; 
HONC)  
 
 
 
 
 
 
BIOMARKERS OF NICOTINE 
Cotinine  





 
D.  Detailed Study Procedures 
Baseline Session: 
This is a completely remote, virtual study protocol and all sessions will be conducted via video conferencing 
software (e.g., zoom).  
Prior to the start of the baseline session, the participant will be sent a personalized link to a video conferencing 
system (e.g., zoom). At the start of the baseline session, the participant must confirm that they are in a location 
where they can conduct the session, away from other people. The orientation session will occur.  First, the 
study staff will confirm that the participant has a computer, laptop, tablet, or similar device with internet access 
that allows them to use video conferencing and complete REDCap surveys. The device must have a working 
camera, microphone, and audio.  Second, the participant will answer questions to determine study eligibility 
and to confirm that the participant does not have COVID-19 via self-report. Third, study staff will review the 
informed consent and the informed consent must be signed by the participant prior to the administration of the 
baseline survey or the start of any study procedures. Fourth, the participant will read over the electronic 
informed consent form (ICF) and be given the opportunity to ask any questions that they may have. Prior to 

 
  
9 
 
signing the ICF, the participant will complete the consent quiz to assess their understanding of the study and 
their responsibilities. The study team member will then review any incorrect questions with the participant. After 
completing the consent quiz, the participant and study team member will electronically sign the informed 
consent form available in REDCap, if the participant agrees to participate in the study. A copy of the signed 
consent form will be emailed to the participant for their record.  
For the baseline session, and visits for Day 1, 3-, 6-, 9-, 12-month sessions, participants will receive reminders 
through text, phone reminders, and/or Twilio/Apptoto. Upon completion of the consent, the study team member 
will then confirm the participant's address to receive all equipment and materials needed to conduct the study 
at home The participant will provide their availability to receive the study materials. If the participant is 
unavailable to receive the study package, another representative may receive the package instead. 
Participants will be asked to provide their social media contact information on a contact form. This information 
will only be used to contact participants if they change their address and/or phone number. We will not use this 
information to follow participants or collect information about them. Participants will receive a personalized link 
to the baseline study questionnaire, depending on if the person is a parent, adolescent, or young adult to 
complete while awaiting the receipt of the study materials.  
Provision of Study Materials: 
Between the baseline session and the first day of study participation, study products and other materials will be 
prepared and transported to the participant. Study materials will be prepared at our facility by staff. They will 
prepare a package with the requisite equipment and specimen collection materials to be picked up by the 
shipping/courier service. To ensure receipt of the package, the study team will track the location of the 
package and inform the participant of any updates. Materials will include: disposable protective gloves, alcohol 
wipes, pregnancy  test (including a urine cup for collection to complete the test), a spirometer and nasal swab 
(NELF) kits. In addition, a package insert will be included inside the package to detail the materials/supplies 
that are included. With the arrival of the study materials, the study team will contact the participant to schedule 
the first of five (5) EMA 2-week assessment monitoring bursts. 
Study Session - Day 1 
Once the participant has completed the consent and baseline questionnaires, and received the study 
materials, they will attend the Day 1 study session. This session will last up to 30 minutes. At the start of the 
session, the participant will be instructed to put on the enclosed gloves and wipe down the spirometer and one 
nasal swab (NELF) collection kit. The study team member will instruct the participant on how to complete the 
twice-daily ecological momentary assessments (EMA) questionnaires during each 2-week EMA study period 
through the secure smartphone application, RealLife Exp, by LifeData LLC. Participants will be provided 
instructions on how to download the application on their smartphone, how to download the relevant study 
survey package, and how to enter their study ID. This application will push survey notifications to participants’ 
phones in the morning and evening each day corresponding to their sleep/wake cycle (assessed at baseline). 
If participants does not complete the EMA survey immediately, RealLife Exp will send a reminder notification 
every 30 minutes to encourage survey completion. Prompts not completed within 90 minutes (5 reminders 
total) will disappear and be marked as missed. EMA surveys will assess current mood, nicotine craving, 
nicotine withdrawal symptoms, stress, recency of vaping/OTP use, current setting, frequency and quantity of 
EC and/or OTP use (since the previous assessment), flavors, nicotine concentration, and EC device used. 
EMA assessments will take less than 5 minutes to complete. All EMA assessments will be date and time 
stamped for future analyses.  
The study team member will then show the participant how to use the spirometer using an instruction video. 
Participants will be prompted to complete twice daily spirometry assessments following completion of the 
daytime and nighttime EMA surveys. Step-by-step directions to complete the spirometry test will be provided. 
The test provides a complete pulmonary function test in less than 2 minutes using the Spirobank application. 

 
  
10 
 
Results of spirometry tests include peak flow and FEV1/FVC. All spirometry data are date and time stamped 
and saved within the application to a secure server. The study team member will instruct the participant on how 
to collect the nasal swab specimens and review videos that demonstrate the appropriate collection techniques. 
At each virtual session (3-, 6-,9-,12-month visits), participants will also complete nasal swab collection. Step-
by-step directions to complete the collection and return it to the lab will be provided with the study team 
member facilitating picking up the specimen. Participants will be instructed to place specimens and the freezer 
pack in their freezer (for no more than one week) until the pick-up. Prior to the end of the session, the staff will 
request that the participant either take a picture of their e-cigarette device and e-liquid or show the study team 
member their e-cigarette device and e-liquid. The information will allow the study team to code for e-cigarette 
device specifications (i.e., voltage, disposable e-cigarette device, etc) to better understand participant 
preferences.  
Never/non-users will also complete up to a 30 minute individual interview with a study team member who will 
ask about reasons for non-use. To protect the anonymity of the participants, staff will instruct the participant 
turn off their camera and complete the interview with only their participant ID on the zoom screen. We never 
conduct the video or record the session with their camera on to protect their anonymity. Upon the verbatim 
transcription of the session, we will completely delete the zoom video recording. In addition, we only begin 
recording when the participant has turned off their camera and end the recording before their camera to turned 
on again. All videos will be deleted at the end of the study and only the verbatim transcripts will be used for 
qualitative data analyses. After the interview, study staff will complete a debrief form to assess interview 
saturation. This is helpful to determine when/if all topics related to non-use have been discussed. The audio of 
the interview will be recorded and transcribed (both will be saved on a secure server and coded with the 
participant's study identifier). 
EMA Study Session - 2 week following Day 1, then 2-weeks prior to each virtual visit (3-, 6-, 9-, 12-
month sessions) 
The participant will continue inputting EMA surveys and utilizing the spirometer for a 2-week period. All 
participants will complete twice-daily Ecological Momentary Assessment (EMA) monitoring “bursts” for the 2-
weeks prior to each scheduled zoom visit through RealLife Exp, a secure smartphone application by LifeData 
LLC. The LifeData platform (www.lifedatacorp.com) will be used to develop the application and securely collect 
data. The participants will be instructed to download the LifeData application on their smartphone and to 
download the relevant study survey package to start participation. Prompts that are not completed within 90 
min of the notification alert will disappear and will be marked as missed. Consistent with our team’s previous 
studies, EMA surveys will assess current mood, nicotine craving, nicotine withdrawal symptoms, stress, 
recency of vaping/OTP use, current setting, frequency and quantity of EC and/or OTP use (since the previous 
assessment), flavors, nicotine concentration, EC device used, and satisfaction and pleasure from about their 
most recent EC use. Based on Dr. Tackett’s prior experience, EMA assessments take <5 minutes to complete. 
All EMA assessments will be date- and time-stamped for future analyses. Participants will be prompted to 
complete twice daily spirometry assessments following completion of the daytime and nighttime EMA surveys. 
Step-by-step directions to complete the spirometry test will be provided. The test is simple, easy to use, and 
provides a complete pulmonary function test in < 2 minutes. All spirometry data are date and time stamped and 
saved within the application to a secure server. At the end of the 12 Month visit, their participation in the study 
is complete. 
3-, 6-, 9-, 12-Month Sessions 
Prior to each session, EC-users will complete questionnaires similar to the baseline assessment (e.g., EC use, 
OTP use, demographics, respiratory health, etc.). Participants are asked to complete these questionnaires 
before the start of the session. At the session, the study staff will check in on how the study is going, use of the 
spirometer/EMA applications and answer any questions the participants may have. Each session will last about 

 
  
11 
 
1 hour. Prior to each session, never/non users will complete questionnaires similar to the baseline assessment 
(e.g., any EC use, OTP use, demographics, respiratory health, etc). Participants are asked to complete these 
questionnaires before the start of the session. At the session, the study stuff will check in on how the study is 
going, use of the spirometer/EMA applications and answer any questions the participants may have. 
Never/non-users will also complete up to a 30-minute individual interview with a study team member who will 
ask about reasons for non-use. Study staff will complete the debrief form to assess interview saturation. This is 
helpful to determine when/if all topics related to non-use have been discussed. Each session will last up to 1 
hour. The study team member will instruct the participant on how to collect the nasal swab specimens and 
review videos that demonstrate the appropriate collection techniques. At each virtual session (3-, 6-,9-,12-
month visits), participants will also complete nasal swab collection. Step-by-step directions to complete the 
both collections and return them to the lab will be provided with the study team member facilitating picking up 
the specimen. Participants will be instructed to place specimens and the freezer pack in their freezer (for no 
more than one week) until the pick-up. 
Final Visit 12-month session 
Participants will complete their final session by answering questionnaires similar to the baseline assessment 
(e.g., any EC use, OTP use, demographics, respiratory health, etc.), final nasal sample, and a questionnaire 
asking about their self-reported rating of how the study went and any thoughts about their responses. When 
participants return their final nasal sample, they will also be asked to return their spirometry device.Protection 
Against Risk:  
The research protocol calls for current exclusive- EC and never-users (never tobacco users). Those who 
participate in this study will be asked questions about EC use and other tobacco product (OTP) use. Currently 
ECs are the most commonly used tobacco product among adolescents and young adults. We will never provide 
any tobacco products to participants, encourage participants to begin using ECs or OTPs, and will provide 
smoking cessation to those interested or ask about referrals at each visit. Questionnaires, respiratory 
assessments, and NELF collection procedures are all non-invasive and involve minimal risk to study participants. 
Potential risks are as follows: a) risk of using ECs, b) dual use of cigarettes and ECs, c) loss of confidentiality or 
privacy, and d) potential for undermining smoking cessation.  
  
F.2.B. Adequacy of Protection against Risks  
Recruitment and Informed Consent: At first contact, all participants will be screened according to the studies 
inclusion/exclusion criteria. Those who are eligible will be given a brief verbal overview of the study and invited 
to participate. Informed consent (including a description of the nature, purpose, risks, and benefits of the study) 
will take place through oral explanation of the study. The voluntary nature of the study and the participant’s right 
to withdraw at any time will be stressed during the consent process; a copy of the informed consent will be 
provided to the participant in written form at the time of consent for them to keep. Informed consent will be 
collected by IRB-approved study personnel. Recruitment script and materials, consent forms and all study 
procedures will be approved by the OSU Institutional Review Board. All participants will provide consent before 
any study data is collected.  
  
F.2.C. Protections Against Risk:  
 
Risk of using ECs: The risk of side effects and adverse events are very low. These products are sold online, 
and at EC specialty stores and convenience stores nationwide, without a prescription. Nevertheless, all 
participants will be screened for general medical precautions (e.g., pregnancy, cardiovascular disease) and 
monitored for adverse events during the study period. Study personnel will assess for adverse events via self-
report at all follow-up visits. Any serious adverse events will be reported to the study’s DSMB and then to the 
OUHSC IRB and to the NIH. We will withdraw participants who have a serious adverse event, or become 
pregnant or begin to breastfeed. The most likely adverse (potential for nicotine overdose) event is anticipated to 
be rare (<5% in our team’s previous studies) and mild (nausea, headache, disrupted sleep), and will be handled 
quickly (i.e., advice to participant to reduce or stop EC use). Lab studies of toxin exposure suggest that ECs 
incur no greater risk to health than do conventional cigarettes. Indeed, ECs generally show lower levels of 

 
  
12 
 
harmful and potentially harmful constituents. To date, five EC studies discuss adverse events (3 survey and 2 
randomized clinical trials), reporting mild and tolerable side effects that generally resolved completely over time 
with continued use (90% of cases); the most predominant of which were mouth/throat irritation, cough, and 
headache. In both randomized clinical trials, no serious adverse events were reported and the EC group and the 
nicotine patch group had comparable levels of adverse events. The most common were mouth irritation, throat 
irritation, dry cough and headache. Further, participants will be using their own EC device and we will never 
provide tobacco products to young adults at any time.   
  
Risk of dual use of cigarettes and ECs: The concern of EC users engaging in dual use is that they will 
substantially increase their uptake of nicotine, leading to nicotine overdose. The symptoms of nicotine overdose 
include nausea, vomiting, dizziness, headache, and rapid heart rate. In our previous trials with ECs, none of the 
participants reported any indication of nicotine overdose in their dual use of ECs and OTP. The literature 
indicates33,38,40,79,80 that, at most, 20% of the participants enrolled in the proposed study will become a dual user 
over the 1-year period (estimated n = 30). We will provide free smoking cessation referrals for young adults and 
provide informational resources regarding the risks of dual using ECs with combustible OTPs (see Potential for 
Undermining Cessation below).  
 
Loss of Confidentiality and Privacy: Confidentiality will be maintained by numerically coding all data, 
disguising identifying information, and keeping data locked in file drawers or in a secure, password protected 
database. All biospecimen samples are kept in a locked freezer and also will be deidentified. Names of 
participants will be kept in separate from participant data. Only study research assistants and the PI will have 
the information that connects participant’s name and ID number. All electronic data will be numerically coded 
and stored in a password protected database, on a password protected computer in a secure research space.  
  
EMA Confidentiality Procedures. The following features are designed to address smartphone/EMA data 
security issues: 1) the data stored on the smartphone device is in a SQLite database in a sandbox environment 
where read/write operations are only available through the programming application. No file or output is readable 
to end users, 2) a password (only known to researchers) is required to authenticate the current user before data 
can be downloaded from the smartphone device to the server, 3) the web browser application linking the principal 
investigator’s computer to the database is on HTTPS protocol (SSL certificate with encryption) which will 
guarantee the data transfer from web browser to the backend database is well protected. Data will be 
downloaded frequently and saved on OSU approved servers (e.g., T-drive at the Center for Tobacco Research) 
which meets OSU security requirements. . Participant information will be accessible only to research staff, who 
are pledged to confidentiality and complete training in the ethical conduct of research (i.e., both HIPAA and CITI 
trainings). Identifying information will never be reported in any publication.  
  
Potential for Undermining Cessation: The study sample is comprised of current exclusive-EC and never-
users. We will never ask users who are in the process of quitting to stop. At the end of the study, all participants 
will be debriefed and educated about ECs and OTP. This education will include the information that:  
a) there is no safe cigarette, b) the best thing a smoker can do to improve health is to quit, c) some ECs are 
manufactured by the tobacco industry, d) ECs, though able to be regulated by the FDA as a tobacco product, 
are largely unregulated by the FDA until they are able to develop appropriate guidelines, and e) it is unclear 
whether ECs reduce the risks associated with smoking. The PI and Primary Mentor will be available for any 
questions that participants may have about ECs, smoking, or smoking cessation. It is important to note that the 
use of ECs incurs will be no greater harm, as the participants in the “user” group have already decided on his/her 
own to use the product. While some young adults in the present study will be under the legal age of tobacco 
use, ECs are available online and over-the-counter at various convenience stores, EC specialty stores and 
places where tobacco products are sold. Further, we will never provide any product to young adults. Among 
those screened and ineligible/uninterested, referral resources for smoking cessation will be provided for those 
who inquire. Among study participants, information on cessation resources will be provided at the final visit and 
participants will be told that if at any time during the study they are interested in smoking cessation services, a 
list of free smoking cessation resources will be provided, including the Quit line.  
  
Adverse Events:  

 
  
13 
 
 
All observed or volunteered adverse events regardless of tobacco use status (exclusive EC-user or never-user) 
will be recorded on the adverse event page(s) of the Adverse Event Form. Exacerbation of pre-existing illness 
is defined as a manifestation (sign or symptom) of the illness that indicates a significant increase in the severity 
of the illness as compared to the severity noted at the start of the study. It may include worsening or increase in 
severity of signs or symptoms of the illness, increase in frequency of signs and symptoms of an intermittent 
illness, or the appearance of a new manifestation/complication. Exacerbation of a pre-existing illness should be 
considered when a patient/subject requires new or additional concomitant medication or non-medication therapy 
for the treatment of that illness during the study. Lack of or insufficient clinical response, benefit, efficacy, 
therapeutic effect, or pharmacologic action should not be recorded as an adverse event.  
 
For all adverse events, Drs. Tackett and Wagener will pursue and obtain information adequate both to determine 
the outcome of the adverse event and to assess whether it meets the criteria for classification as a serious 
adverse event requiring immediate notification to OSU IRB/ NIH. For all adverse events, sufficient information 
should be obtained by Drs. Tackett and Leventhal to determine the causality of the adverse event (i.e., other 
illness). Drs. Tackett and Wagener is required to assess causality and indicate that assessment on the Case 
Report Form. Follow-up of the adverse event, after the date of therapy discontinuation, is required if the adverse 
event or its sequelae persist. Follow-up is required until the event or its sequelae resolve or stabilize at a level 
acceptable to the investigator or his/her designated representative.  
 
All serious adverse events will be reported immediately to Dr. Brown then to IRB and the NIH. Important medical 
events that may not result in death, be life-threatening, or require hospitalization may be considered serious 
adverse events when, based upon appropriate medical judgment, they may jeopardize the patient/subject and 
may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Any serious 
adverse event or death must be reported immediately independent of the circumstances or suspected cause if 
it occurs or comes to the attention of the principal investigator at any time during the study through the last follow-
up visit required by the protocol. Any serious adverse event occurring at any other time after completion of the 
study must be promptly reported. For all serious adverse events, the investigator is obligated to pursue and 
provide information as requested by the DSMB in addition to that on the Adverse Event Form. In general, this 
will include a description of the adverse event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality. Information on other possible causes of the event, 
including concomitant medications and illnesses, must be provided. The investigator’s assessment of causality 
must also be provided. Drs. Tackett and Wagener will ensure that information reported immediately by telephone 
or other means and information entered in the Adverse Event Form are accurate and consistent. 
  
We will monitor for risk of using ECs by screening participants for general medical precautions. The most likely 
adverse event (potential for nicotine overdose) is anticipated to be rare and mild based on Dr. Wagener’s 
previous studies, and will be handled quickly (i.e., advice to participant to reduce or eliminate nicotine use). Lab 
studies of toxin exposure suggest that EC incur no greater risk to health than do combustible cigarettes. Dr. 
Tackett and study personnel will be available for any questions that participants may have about ECs, smoking, 
or smoking cessation. Any adverse events, breaks of confidentiality, or any other data or safety issues that arise 
will be discussed immediately between study personnel and Drs. Tackett and Wagener.  
 
 
E. Internal Validity 
 
Quality assurance: Procedures in place to ensure the validity and integrity of the data. It will be made clear 
to participants that all information obtained during assessments is confidential and that no information will 
be shared with the participants’ clinicians unless the participant requests this in writing. All investigators 
and staff associated with this project have been trained, and new hires will be trained on human research 
ethics in accordance with the requirements of the local institutions during initial project approval. 
 
Drs. Tackett and Wagener will train and closely monitor the Research Assistants on the procedures to be 

 
  
14 
 
used in this study. Such monitoring will consist of frequent in-person discussion of study visits at the 
beginning of the study and less frequent monitoring as the study progresses. 
 
Participants will be trained during the Day 1 Session on how to operate the study app, and participants 
will have a chance to ask any questions during the subsequent calls. The app will remind participants 
about when to complete assessments. 
 
Data will be collected in a consistent manner across all years of the study. Standard operating procedures 
will be developed. 
 
Data collection/entry/transmission/analysis: Many subjective measures will be administered using our study 
app, MyCap. MyCap syncs with RedCap, and thus, all data are entered directly into a RedCap database 
via the study app. These will be identified by Subject Identifier. Forms will include programming features to 
ensure valid data (i.e., input masks, validation criteria, skip logic) and will be stored at the Ohio State 
University. 
 
F. Data Analyses 
 
Power Analyses. For Aims 1 and 2: The use of repeated measures and longitudinal methodology allow for 
greater detection of moderate effect sizes associated with decreased in markers of respiratory health, increases 
in nicotine addiction, changes in EC and/or OTP use patterns, and frequency/quantity of EC use. For each 
repeated measures analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA) we are 95% 
powered to find moderate effect sizes. For Aim 3: Power was calculated using MPlus Monte Carlo estimation 
informed by published and preliminary studies. To test power for MLM, we first examined power with Optimal 
Design using repeated measures. We then repeated our power analyses in MPlus Monte Carlo estimation, 
building on published MLM simulations and using 1000 replications to confirm stability of each model, to better 
capture the complexity of the separate models, including cross-level interactions.  For the EMA analyses, the 
power of the statistical test depends on the total effective sample size (ESS) and the statistical model used. The 
total ESS is the number of statistically independent observations available for this study. The number of 
statistically independent observations is the total number of observations (number of participants x number of 
data collections) adjusted for within-individual correlations. As the within-individual, or intra-class, correlation 
(ICC) increases, the ESS decreases. The following formula illustrates this relationship, whereby the effective 
sample size is equal to nm/(1+(m-1)ρ), where n = number of participants; m = number of repeated measures for 
each participant; and ρ = ICC.94 In sum, even assuming effects as small as .10 (well below expected effect), we 
will be well powered (> .85) to identify effects across analyses.  
 
Data Analytic Overview. Analyses will be conducted using SAS, R and MPlus. For Aims 1 and 2, distribution 
plots will be carried out on all data to assess for normality, and any non-Gaussian data were evaluated with 
either Wilcoxon signed rank test or, where appropriate, data will be logarithmically transformed before analysis. 
Comparisons of continuous data will be made by an overall analysis of variance, followed by Bonferroni 
corrected, multiple-range testing, to obviate multiple pairwise comparisons, with the overall α error set at .05 
(2tailed). For Aim 3, as appropriate, alternate estimators to address expected and observed characteristics (e.g., 
Poisson distribution, zero-inflation) will be used.  MPlus permits frequentist and Bayesian estimation for models 
with missing data. Bayesian procedures allow multiple imputation of multiple datasets subsequently used with 
parameter estimates averaged across imputed datasets. Multiple imputation will virtually always outperform older 
methods of managing missing data (e.g., listwise deletion) with regard to both accuracy and power, making it 
the preferred approach.72, 73 Measurement models will be formally tested. If analyses do not support the presence 
of the expected unitary constructs, subsequent analyses will examine aims as defined by observed variables. 
Model invariance tests will also be used to assess appropriate statistical treatment of gender; if measurement 
invariance is not observed, analyses will be stratified by gender. Aim 1: Hypotheses 1a and 1b: We will use two-
way repeated measures ANOVA and MANOVA with Tukey adjustment to examine differences between the 
measures of respiratory health (pulmonary functioning, NELF samples) and EMA data (five two-week monitoring 
periods). For H1a, two-way repeated measures ANOVA will compare mean differences between pulmonary and 

 
  
15 
 
respiratory markers and user status (EC-exclusive vs. never-users). For H1b, we will use MANOVA models to 
examine changes in frequency/quantity of EC use and nicotine dependence (significant increases in HONC 
scores) across each session with respiratory and pulmonary functioning. Aim 2 Hypotheses 2a and 2b: We will 
use two-way repeated measures analysis of variance and multivariate analysis of variance with Tukey-
adjustment to examine differences between the number of vape sessions per day and time spent vaping with 
pulmonary functioning across each EMA monitoring period. For H2a, two-way repeated measures ANOVA will 
compare mean differences between pulmonary and frequency/quantity of EC use. For H2b, we use MANOVA 
models to examine changes in pulmonary functioning and the experimentation of OTP in conjunction with EC-
use across the 1-year monitoring period. Exploratory Aim 3: Hypotheses H3a: We will use multilevel models 
(MLM) to examine the daily-level associations between the frequency/quantity of EC use experimentation and 
pulmonary functioning. These models will allow us to examine the within-person associations between EC use 
and pulmonary functioning, using Curran and Baurer’s95 procedures for disaggregating within-person and 
between-person effects using two level analysis in multilevel modeling. These models will also allow for the 
examination of cross-level interactions among between and within-person factors. Specifically, we will be able 
to examine the role of daily within-person fluctuations in frequency/quantity of EC use in its links to pulmonary 
functioning. Further, we will be able to assess the potential differences by user status as well as baseline 
respiratory health. Significant interactions will be probed using Preacher, Curran, & Bauer’s96 computational 
tools. The applicant has integrated training in these techniques into her goals (Goal #4). 
 
IV. Bibliography 
1. 
Pai AL, Tackett A, Ittenbach RF, Goebel J. Psychosocial Assessment Tool 2.0 _General: 
validity of a psychosocial risk screener in a pediatric kidney transplant sample. Pediatric 
transplantation. 2012;16(1):92-98.  
2. 
Pai AL, Rausch J, Tackett A, Marsolo K, Drotar D, Goebel J. System for integrated adherence 
monitoring: Real‐time non‐adherence risk assessment in pediatric kidney transplantation. Pediatric 
transplantation. 2012;16(4):329-334.  
3. 
Pai AL, Tackett A, Hente EA, Ernst MM, Denson LA, Hommel KA. Assessing psychosocial 
risk in pediatric inflammatory bowel disease: validation of the Psychosocial Assessment Tool 2.0 
_General. Journal of pediatric gastroenterology and nutrition. 2014;58(1).  
4. 
Tackett AP, Peugh JL, Wu YP, Pai AL. Parent Medication Barriers Scale (PMBS): A 
preliminary investigation of factor structures with hematopoietic stem cell transplant recipients. 
Children's Health Care. 2016;45(2):177-191.  
5. 
Tackett AP L, W.V., Meier, E, Suorsa, K.I, Wagener, T.L, & Mullins, L.L. Tobacco usestatus 
as a function of health care utilization attitudes/beliefs. The Association for Behavioral and Cognitive 
Therapies; 2013; Nashville, TN.  
6. 
Tackett AP, Leavens EL, Wiedenmann A, et al. Preliminary exploration of secondhand smoke 
exposure in youth with Sickle Cell Disease: biochemical verification, pulmonary functioning, and 
health care utilization. Psychology, health & medicine. 2018:1-8.  
7. 
Turner E, Fedele DA, Thompson L, Salloum RG. Patterns of electronic cigarette use in youth 
with asthma: Results from a nationally representative sample. Annals of Allergy, Asthma & 
Immunology. 2018;120(2):220-222.  
8. 
Reid KM, Forrest JR, Porter L. Tobacco Product Use Among Youths With and Without 
Lifetime Asthma—Florida, 2016. Morbidity and Mortality Weekly Report. 2018;67(21):599.  
9. 
Choi K, Bernat D. E-cigarette use among Florida youth with and without asthma. American 
journal of preventive medicine. 2016;51(4):446-453.  
10. 
Schweitzer RJ, Wills TA, Tam E, Pagano I, Choi K. E-cigarette use and asthma in a 
multiethnic sample of adolescents. Preventive medicine. 2017;105:226-231.  
11. 
Tackett, A.P., Keller-Hamilton, B., Hébert, E.T., Smith, C.E., Metcalf, J., Queimado, L., 
Stevens,  
E.M., Wallace, S., McQuaid, E.L. & Wagener, T.L. (in press). Associations of Respiratory Symptoms 
among Youth E-Cigarette Users: Results from the PATH Study.  JAMA Network Open.   

 
  
16 
 
12. 
Roberts CM, Tackett, A.P. Leavens, E.L.S., Edwards, C., Stevens, E.M., Hébert, E.L., Villanti, 
PhD, A.C., Pearson, J.L., & Wagener, T.L. . JUUL Perceived Drug Effects and Preferences between 
Emerging Adults, Young Adults, and Older Adults. under review.  
13. 
Tackett A, Edwards, C, Roberts, CM, Stevens, E, Leavens, ELS, and Wagener, TL. 
Examining Other Tobacco and Marijuana Use Among Experimenters and Current Users of JUUL. 
under review.  
14. 
Searby L, Ballenger J, Tripses J. Climbing the ladder, holding the ladder: The mentoring 
experiences of higher education female leaders. Advancing Women in Leadership. 2015;35:98-107.  
15. 
United States Department of Health and Human Services. The health consequences of 
smoking—50 years of progress: a report of the Surgeon General. Atlanta, GA: US Department of 
Health and Human Services, Centers for Disease Control and Prevention, National Center for 
Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2014;17.  
16. 
United Stated Department of Health and Human Services. A Report of the Surgeon General; 
US  
Department of Health and Human Services, Centers for Disease Control and Prevention. National 
Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health: 
Atlanta, GA, USA. 2016.  
17. 
Carpenter CM, Wayne GF, Pauly JL, Koh HK, Connolly GN. New cigarette brands with flavors 
that appeal to youth: tobacco marketing strategies. Health Affairs. 2005;24(6):1601-1610.  
18. 
Gostin LO, Glasner AY. E-cigarettes, vaping, and youth. Jama. 2014;312(6):595-596.  
19. 
Lempert LK, Glantz S. Packaging colour research by tobacco companies: the pack as a 
product characteristic. Tobacco control. 2017;26(3):307-315.  
20. 
Zhu S-H, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and 
counting: implications for product regulation. Tobacco control. 2014;23(suppl 3):iii3-iii9.  
21. 
Gibson-Young LM. JUULING: What kids don’t know will hurt them. Pediatrics. 2018;35(6).  
22. 
Goniewicz ML, Boykan R, Messina CR, Eliscu A, Tolentino J. High exposure to nicotine 
among adolescents who use Juul and other vape pod systems (‘pods’). Tobacco control. 
2018:tobaccocontrol2018-054565.  
23. 
Huang J, Duan Z, Kwok J, et al. Vaping versus JUULing: how the extraordinary growth and 
marketing of JUUL transformed the US retail e-cigarette market. Tobacco control. 
2018:tobaccocontrol-2018054382.  
24. 
Willett JG, Bennett M, Hair EC, et al. Recognition, use and perceptions of JUUL among youth 
and young adults. Tobacco control. 2018:tobaccocontrol-2018-054273.  
25. 
Kiljander T, Helin T, Venho K, Jaakkola A, Lehtimäki L. Prevalence of asthma–COPD overlap 
syndrome among primary care asthmatics with a smoking history: a cross-sectional study. NPJ 
primary care respiratory medicine. 2015;25:15047.  
26. 
Usmani OS, Singh D, Spinola M, Bizzi A, Barnes PJ. The prevalence of small airways 
disease in adult asthma: a systematic literature review. Respiratory medicine. 2016;116:19-27.  
27. 
Torres A, Blasi F, Dartois N, Akova M. Which individuals are at increased risk of 
pneumococcal disease and why? Impact of COPD, asthma, smoking, diabetes, and/or chronic heart 
disease on communityacquired pneumonia and invasive pneumococcal disease. Thorax. 
2015:thoraxjnl-2015-206780.  
28. 
Liu Y, Pleasants RA, Croft JB, et al. Smoking duration, respiratory symptoms, and COPD in 
adults aged≥ 45 years with a smoking history. International journal of chronic obstructive pulmonary 
disease. 2015;10:1409.  
29. 
Dhariwal J, Tennant RC, Hansell DM, et al. Smoking cessation in COPD causes a transient 
improvement in spirometry and decreases micronodules on high-resolution CT imaging. Chest. 
2014;145(5):1006-1015.  
30. 
Leone FT, Carlsen K-H, Chooljian D, et al. Recommendations for the Appropriate Structure,  

 
  
17 
 
Communication, and Investigation of Tobacco Harm Reduction Claims. An Official American 
Thoracic Society Policy Statement. American journal of respiratory and critical care medicine. 
2018;198(8):e90e105.  
31. 
Abram A, Zeller M. FDA’s New Plan to Combat Tobacco’s Staggering Public Health Toll. 
Annals of the American Thoracic Society. 2018(ja).  
32. 
Tsai J, Walton K, Coleman BN, et al. Reasons for electronic cigarette use among middle and 
high school students—National Youth Tobacco Survey, United States, 2016. Morbidity and Mortality 
Weekly Report. 2018;67(6):196.  
33. 
Leventhal AM, Strong DR, Kirkpatrick MG, et al. Association of electronic cigarette use with 
initiation of combustible tobacco product smoking in early adolescence. Jama. 2015;314(7):700-707.  
34. 
Wang TW, Gentzke A, Sharapova S, Cullen KA, Ambrose BK, Jamal A. Tobacco Product Use 
Among Middle and High School Students—United States, 2011–2017. Morbidity and Mortality 
Weekly Report. 2018;67(22):629.  
35. 
Truth Inititaive. Tobacco Rates in Oklahoma. 2018; https://truthinitiative.org/tobacco-use-
oklahoma.  
36. 
McGinley L. FDA chief calls youth e-cigarettes and 'epidemic'. The Washington Post. 
September 12, 2018, 2018.  
37. 
Rohde JA, Noar SM, Horvitz C, Lazard AJ, Ross JC, Sutfin EL. The Role of Knowledge and 
Risk Beliefs in Adolescent E-Cigarette Use: A Pilot Study. International journal of environmental 
research and public health. 2018;15(4).  
38. 
Soneji S, Barrington-Trimis JL, Wills TA, et al. Association between initial use of e-cigarettes 
and subsequent cigarette smoking among adolescents and young adults: a systematic review and 
metaanalysis. JAMA pediatrics. 2017;171(8):788-797.  
39. 
Miech R, Patrick ME, O'malley PM, Johnston LD. E-cigarette use as a predictor of cigarette 
smoking: results from a 1-year follow-up of a national sample of 12th grade students. Tobacco 
control. 2017:tobaccocontrol-2016-053291.  
40. 
Barrington-Trimis JL, Urman R, Berhane K, et al. E-cigarettes and future cigarette use. 
Pediatrics. 2016;138(1):e20160379.  
41. 
Primack BA, Soneji S, Stoolmiller M, Fine MJ, Sargent JD. Progression to traditional cigarette 
smoking after electronic cigarette use among US adolescents and young adults. JAMA pediatrics. 
2015;169(11):1018-1023.  
42. 
Wills TA, Knight R, Sargent JD, Gibbons FX, Pagano I, Williams RJ. Longitudinal study of e-
cigarette use and onset of cigarette smoking among high school students in Hawaii. Tobacco control. 
2017;26(1):34-39.  
43. 
Chassin L, Presson CC, Pitts SC, Sherman SJ. The natural history of cigarette smoking from 
adolescence to adulthood in a midwestern community sample: multiple trajectories and their 
psychosocial correlates. Health Psychology. 2000;19(3):223.  
44. 
Hair E, Bennett M, Williams V, et al. Progression to established patterns of cigarette smoking 
among young adults. Drug and alcohol dependence. 2017;177:77-83.  
45. 
Chen K, Kandel DB. The natural history of drug use from adolescence to the mid-thirties in a 
general population sample. American journal of public health. 1995;85(1):41-47.  
46. 
Soneji S, Sargent J, Tanski S. Multiple tobacco product use among US adolescents and 
young adults. Tobacco control. 2016;25(2):174-180.  
47. 
Bombard JM, Rock VJ, Pederson LL, Asman KJ. Monitoring polytobacco use among 
adolescents: do cigarette smokers use other forms of tobacco? Nicotine & Tobacco Research. 
2008;10(11):1581-1589.  
48. 
Cavazos‐Rehg PA, Krauss MJ, Spitznagel EL, Grucza RA, Bierut LJ. Youth tobacco use type 
and associations with substance use disorders. Addiction. 2014;109(8):1371-1380.  
49. 
Benowitz NL. Nicotine addiction. New England Journal of Medicine. 2010;362(24):2295-2303.  

 
  
18 
 
50. 
DiFranza JR, Savageau JA, Fletcher K, et al. Susceptibility to nicotine dependence: the 
Development and Assessment of Nicotine Dependence in Youth 2 study. Pediatrics. 
2007;120(4):e974-e983.  
51. 
Wheeler KC, Fletcher KE, Wellman RJ, Difranza JR. Screening adolescents for nicotine 
dependence:  
the Hooked On Nicotine Checklist. Journal of Adolescent Health. 2004;35(3):225-230.  
52. 
Peirsman EJ, Carvelli TJ, Hage PY, et al. Exhaled nitric oxide in childhood allergic asthma 
management: a randomised controlled trial. Pediatric pulmonology. 2014;49(7):624-631.  
53. 
Moradzadeh R, Mansournia MA, Baghfalaki T, Nadrian H, Gustafson P, McCandless LC. The 
impact of maternal smoking during pregnancy on childhood asthma: adjusted for exposure 
misclassification; results from the National Health and Nutrition Examination Survey, 2011–2012. 
Annals of epidemiology. 2018.  
54. 
Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette 
aerosols. 2015.  
55. 
Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as 
tobacco cigarette substitutes: a systematic review. Therapeutic advances in drug safety. 
2014;5(2):67-86.  
56. 
Callahan-Lyon P. Electronic cigarettes: human health effects. Tobacco control. 2014;23(suppl 
2):ii36ii40.  
57. 
Bishop E, Haswell L, Adamson J, Costigan S, Thorne D, Gaca M. An approach to testing 
undiluted e- 
cigarette aerosol in vitro using 3D reconstituted human airway epithelium. Toxicology in Vitro. 2018.  
58. 
Gerloff J, Sundar IK, Freter R, et al. Inflammatory response and barrier dysfunction by 
different ecigarette flavoring chemicals identified by gas chromatography–mass spectrometry in e-
liquids and evapors on human lung epithelial cells and fibroblasts. Applied in vitro toxicology. 
2017;3(1):28-40.  
59. 
Allen JG, Flanigan SS, LeBlanc M, et al. Flavoring chemicals in e-cigarettes: diacetyl, 2, 
3pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavored 
ecigarettes. Environmental health perspectives. 2015;124(6):733-739.  
60. 
McConnell R, Barrington-Trimis JL, Wang K, et al. Electronic cigarette use and respiratory 
symptoms in adolescents. American journal of respiratory and critical care medicine. 
2017;195(8):1043-1049.  
61. 
Wang MP, Ho SY, Leung LT, Lam TH. Electronic cigarette use and respiratory symptoms in 
Chinese adolescents in Hong Kong. JAMA pediatrics. 2016;170(1):89-91.  
62. 
Ratajczak A, Feleszko W, Smith DM, Goniewicz M. How close are we to definitively 
identifying the respiratory health effects of e-cigarettes? Expert review of respiratory medicine. 
2018(just-accepted). 63.  
Urman R, Barrington-Trimis J, Liu F, et al. Prospective Follow-Up of 
Respiratory Symptoms Among Young Adults with a History of Electronic Cigarette Use. In: C16. 
Cigarette, E-cigarette, and Marijuana Smoking: Human and Mouse Studies. American Thoracic 
Society; 2018:A4451-A4451.  
64. 
Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. 
Shortterm pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, 
impedance, and exhaled nitric oxide. Chest. 2012;141(6):1400-1406.  
65. 
Chun LF, Moazed F, Calfee CS, Matthay MA, Gotts JE. Pulmonary toxicity of e-cigarettes. 
American Journal of Physiology-Lung Cellular and Molecular Physiology. 2017;313(2):L193-L206.  
66. 
Kleinjan M, Engels RC, DiFranza JR. Parental smoke exposure and the development of 
nicotine craving in adolescent novice smokers: the roles of DRD2, DRD4, and OPRM1 genotypes. 
BMC pulmonary medicine. 2015;15(1):115.  
67. 
Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco 
cigarettes on exhaled nitric oxide. Toxicology and applied pharmacology. 2014;278(1):9-15.  

 
  
19 
 
68. 
Dicpinigaitis PV, Chang AL, Dicpinigaitis AJ, Negassa A. Effect of e-cigarette use on cough 
reflex sensitivity. Chest. 2016;149(1):161-165.  
69. 
Manigrasso M, Buonanno G, Fuoco FC, Stabile L, Avino P. Aerosol deposition doses in the 
human respiratory tree of electronic cigarette smokers. Environmental Pollution. 2015;196:257-267.  
70. 
Fernández E, Ballbè M, Sureda X, Fu M, Saltó E, Martínez-Sánchez JM. Particulate matter 
from electronic cigarettes and conventional cigarettes: a systematic review and observational study. 
Current environmental health reports. 2015;2(4):423-429.  
71. 
Farsalinos KE, Spyrou A, Tsimopoulou K, Stefopoulos C, Romagna G, Voudris V. Nicotine 
absorption from electronic cigarette use: comparison between first and new-generation devices. 
Scientific reports. 2014;4:4133.  
72. 
Farsalinos KE, Spyrou A, Stefopoulos C, et al. Nicotine absorption from electronic cigarette 
use:  
comparison between experienced consumers (vapers) and naïve users (smokers). Scientific reports. 
2015;5:11269.  
73. 
Behar R, Davis B, Wang Y, Bahl V, Lin S, Talbot P. Identification of toxicants in cinnamon-
flavored electronic cigarette refill fluids. Toxicology in vitro. 2014;28(2):198-208.  
74. 
Robinson R, Hensel E, Morabito P, Roundtree K. Electronic cigarette topography in the 
natural environment. PloS one. 2015;10(6):e0129296.  
75. 
Hammond D, Fong GT, Cummings KM, Hyland A. Smoking topography, brand switching, and 
nicotine delivery: results from an in vivo study. Cancer Epidemiology and Prevention Biomarkers. 
2005;14(6):1370-1375.  
76. 
Lerner CA, Sundar IK, Yao H, et al. Vapors produced by electronic cigarettes and e-juices 
with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and 
in mouse lung. PloS one. 2015;10(2):e0116732.  
77. 
Gass JC, Germeroth LJ, Wray JM, Tiffany ST. The reliability and stability of puff topography 
variables in non-daily smokers assessed in the laboratory. Nicotine & Tobacco Research. 
2015;18(4):484-490.  
78. 
Salepci B, Caglayan B, Fidan A, et al. The effect of pulmonary function testing on the success 
of smoking cessation. Respiratory care. 2016:respcare. 04490.  
79. 
Barrington-Trimis JL, Urman R, Leventhal AM, et al. E-cigarettes, cigarettes, and the 
prevalence of adolescent tobacco use. Pediatrics. 2016:e20153983.  
80. 
Gilreath TD, Leventhal A, Barrington-Trimis JL, et al. Patterns of alternative tobacco product 
use:  
emergence of hookah and e-cigarettes as preferred products amongst youth. Journal of Adolescent 
Health. 2016;58(2):181-185.  
81. 
Pew Research Center. Teens, Social Media & Technology 2018. 2018; 
http://www.pewinternet.org/2018/05/31/teens-social-media-technology-2018/   
82. 
Watkins SL, Glantz SA, Chaffee BW. Association of noncigarette tobacco product use with 
future cigarette smoking among youth in the population assessment of tobacco and health (PATH) 
study, 2013-2015. JAMA pediatrics. 2018;172(2):181-187.  
83. 
Cox LS, Tiffany ST, Christen AG. Evaluation of the brief questionnaire of smoking urges 
(QSU-brief) in laboratory and clinical settings. Nicotine & Tobacco Research. 2001;3(1):7-16.  
84. 
Wanger JS, Culver BH. Quality standards in pulmonary function testing: past, present, future. 
In: American Thoracic Society; 2016.  
85. 
Spindle TR, Breland AB, Karaoghlanian NV, Shihadeh AL, Eissenberg T. Preliminary results 
of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based 
topography measurement device on plasma nicotine and subjective effects. Nicotine & Tobacco 
Research. 2014;17(2):142-149.  
86. 
Perkins KA, Karelitz JL, Giedgowd GE, Conklin CA. The reliability of puff topography and 
subjective responses during ad lib smoking of a single cigarette. Nicotine & Tobacco Research. 
2011;14(4):490494.  

 
  
20 
 
87. 
Tackett AP, Lechner WV, Meier E, et al. Biochemically verified smoking cessation and vaping 
beliefs among vape store customers. Addiction. 2015;110(5):868-874.  
88. 
Tackett AP, Cushing CC, Suorsa KI, et al. Illness uncertainty, global psychological distress, 
and posttraumatic stress in pediatric cancer: a preliminary examination using a path analysis 
approach.  
Journal of pediatric psychology. 2015;41(3):309-318.  
89. 
Meier EM, Tackett AP, Miller MB, Grant DM, Wagener TL. Which nicotine products are 
gateways to regular use?: First-tried tobacco and current use in college students. American journal of 
preventive medicine. 2015;48(1):S86-S93.  
90. 
Gerend MA, Newcomb ME, Mustanski B. Prevalence and correlates of smoking and e-
cigarette use among young men who have sex with men and transgender women. Drug and alcohol 
dependence. 2017;179:395-399.  
91. 
Buchting FO, Emory KT, Kim Y, Fagan P, Vera LE, Emery S. Transgender use of cigarettes, 
cigars, and e-cigarettes in a national study. American journal of preventive medicine. 2017;53(1):e1-
e7.  
92. 
Johnson SE, Holder-Hayes E, Tessman GK, King BA, Alexander T, Zhao X. Tobacco Product 
Use Among Sexual Minority Adults: Findings From the 2012−2013 National Adult Tobacco Survey. 
American Journal of Preventive Medicine. 2016;50(4):e91-e100.  
93. 
Ganz O, Johnson AL,  
94. 
 AM, et al. Tobacco harm perceptions and use among sexual and gender minorities: findings 
from a national sample of young adults in the United States. Addictive Behaviors. 2018;81:104-108.  
95. 
Diggle P, Liang K-Y, Zeger SL. Longitudinal data analysis. New York: Oxford University 
Press. 1994;5:13.  
96. 
Curran PJ, Bauer DJ. The disaggregation of within-person and between-person effects in 
longitudinal models of change. Annual review of psychology. 2011;62:583-619.  
97. 
Preacher KJ, Curran PJ, Bauer DJ. Computational tools for probing interactions in multiple 
linear regression, multilevel modeling, and latent curve analysis. Journal of educational and 
behavioral statistics. 2006;31(4):437-448.  
 
 
 
V. Appendix A. Nasal epithelial lining fluid (NELF)  Sample Procedure Schematic  
 

 
  
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