Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs

PRIMARY OBJECTIVES:

I. To assess inflammatory changes over 6 weeks for lung and urine biomarkers in smokers in a
clinical trial where smokers are randomized to continued use (n=32), complete switching to
the nicotine standardized research electronic cigarettes (e-cig) (SREC) (n=32), complete
switching to nicotine replacement therapy (NRT) (n=32), dual use (cigarettes [cigs] +
nicotine SREC) (n=32), or nicotine-free SREC (n=32).

OUTLINE: Participants are randomized to 1 of 5 groups.

GROUP I: Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants
continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy
on day 71.

GROUP II: Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week
after bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch
completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a
second bronchoscopy on day 71.

GROUP III: Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week
after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and
switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will
be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day
71.

GROUP IV: Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week
after bronchoscopy, participants learn to use the nicotine-containing SREC for 2 weeks and
use both their usual brand of cigarettes and the nicotine-containing SREC starting day 15 for
8 weeks with the intention of smoking reduction to 5 cigarettes or less per day. Participants
undergo a second bronchoscopy on day 71.

GROUP V: Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 2 days
before the day 15 quit date, participants stop smoking using NRT comprising either patch,
gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.

After completion of study, participants are followed up at 3 months.

Inclusion Criteria:

- Smokers who smoke >= 10 filtered cigarettes/day for >= 1 year

- No unstable or significant medical conditions as determined by medical history to
ensure safety of the subject, to minimize the effects of poor health on biomarker
measures and to maximize compliance to study procedures

- Able to read adequately to complete the survey and related study documents or give
consent

- Subject has provided written informed consent to participate in the study

Exclusion Criteria:

- Regular consumption of roll your own cigarettes

- Immune system disorders requiring medication

- Prior diagnosis of chronic pulmonary disease (e.g., asthma with regular use of
medications, chronic obstructive pulmonary disease [COPD], chronic bronchitis, and
restrictive lung disease)

- Acute bronchitis or pneumonia within 1 year

- Reported history of diagnosed kidney or liver disease

- Any medical disorder that will increase the risk from bronchoscopy, affect biomarker
data, or increase risk of an adverse effect from e-cig use

- General anesthesia within 1 year

- Regular use of inhalant medications in the last 2 months

- Use of antibiotics in prior 30 days

- Use of steroids, including corticosteroids, in prior 30 days

- Allergies to study medications, such as, lidocaine, Versed, fentanyl or Cetacaine

- Allergies to propylene glycol/glycerin or flavors

- History of hypersensitivity to varenicline

- Bronchoscopy or any other lung procedure for any reason within the previous 6 months

- Current or recent (within three months) alcohol or drug abuse problems

- Regularly smoked marijuana within the prior 3 months

- Use of an e-cigarette or other combustible tobacco products in the prior 3 months

- Currently using nicotine replacement or other tobacco cessation products (to minimize
confounding effects of another product) or intention to quit in next three months

- Adverse reaction to previous e-cig use

- Body mass index (BMI) > 40 (risk of unstable airway)

- Pregnant or breastfeeding - if the subject is female, a urine pregnancy test at no
cost to the subject will be done on the day of bronchoscopy

- Unable to read for comprehension or completion of study documents