Effects of E-cigarettes (ECIGs) on Pulmonary Inflammation and Behavior in HIV Infected Smokers

Title: Effects of e-cigarettes (ECIGs) on pulmonary inflammation and behavior in HIV infected
smokers

Purpose of the Study: Even though smoking is the leading cause of preventable disease and
deaths in the U.S., millions of Americans continue to smoke cigarettes, including 16% of
persons in the general population and 40-70% of all HIV-infected patients. In contrast to the
relatively known adverse effects of combustible cigarettes, the rapid emergence of
e-cigarettes have raised numerous questions regarding their health effects which may be
amplified in vulnerable populations and those already immunocompromised such as HIV-infected
patients. The goal of the proposed research is to gain an understanding of the cellular and
inflammatory mechanisms that occur in the lung of HIV-infected smokers who transition from
conventional tobacco cigarettes to e-cigarettes and to characterize their behavioral and
neurocognitive effects. These efforts will provide first in kind data on the effects of ECIGs
in this study population and provide valuable data to develop needed regulatory policies.

Background & Significance: While rates of cigarette smoking are gradually decreasing in the
US, the burden of tobacco abuse among people living with HIV remains undisputedly high with
prevalence estimates two to three times higher than the general population (42.4% vs. 16%).
Although ECIGs likely contain significantly fewer numbers of toxicants compared to
combustible cigarettes, it is not yet clear whether ECIG are less harmful than their
traditional tobacco counterparts and what, if any, effects they have on behavior and
neurocognitive functioning. The biological effects of ECIG on lung health have not yet been
sufficiently characterized due the relatively nascent nature of the field. While combustible
tobacco use induces oxidant stress in the airways of healthy smokers, little work to date has
established the effect of ECIG use on oxidant stress in human airways. Transitioning the
smoker from combustible tobacco to ECIG may decrease lung oxidative stress, improve lung
function and decrease withdrawal symptoms and deficits in neurocognition commonly seen with
tobacco withdrawal.

Design & Procedures: 15 HIV-infected adults will be recruited from the Duke Infectious
Diseases Clinic. In addition, 5 HIV-negative adults will be recruited from the community
through flyers. For this pilot study, 15 willing subjects will receive ECIGs and 5 control
subjects will continue to smoke their chosen usual brand of combustible cigarettes (UB). Each
group will receive either ECIG or UB for a total of 4 weeks and undergo pulmonary and
behavioral assessments during this period. In order to examine pulmonary and behavioral
effects of ECIG in the absence of combustible cigarette use, a mobile contingency management
(mCM) procedure will be used to provide monetary reinforcement for biochemically verified
discontinuation of the use of combustible cigarettes. Participants in the UB group will also
undergo mCM procedures, but contingencies will differ. After 4 weeks, the ECIG group will be
allowed to transition back to their chosen combustible cigarette product for an additional 2
weeks with additional pulmonary and behavioral assessments. All subjects will undergo three
respiratory assessments in the Duke Clinical Research Unit (DCRU). The first respiratory
assessment will occur at study arm assignment (V1) to establish baseline measures of lung
function, oxidative stress, and systemic inflammation. Pulmonary assessments will be repeated
again 4 weeks after transition to ECIG or continued UB use (V4). A final respiratory
assessment (V5) will occur 2 weeks after stopping ECIG or after 6 weeks of continued UB use
to measure changes relative to baseline lung function, oxidative stress, and inflammation.
Neuro-cognitive and behavioral visits will take place in Duke South or at the Center for
Addiction Science and Technology (CfAST) and occur at Visit 2 (mCM transition), and
respiratory visits (V4 & V5) as well as 2 weeks after ECIG transition/ continued UB use (V3)

Inclusion Criteria:

1. Self-reported smoking of ≥10 cigarettes/day for >2yrs

2. Smoke regular filtered cigarettes or machine-rolled cigarettes with a filter

3. Have expired CO concentrations of ≥10ppm or morning urinary cotinine >100ng/ml (as
measured with NicAlert)

- If present in the afternoon with CO concentration >10ppm then no cotinine test

- If less than <10 then urinary continine

4. No serious quit attempt in the prior 3 months. This includes use of any FDA approved
smoking cessation medication (varenicline, bupropion [used specifically as a quitting
aid], patch, gum, lozenge, inhaler, and nasal spray) in the past 3 months as an
indication of treatment seeking

5. No plans to quit in the next 3 months (set quit date, designated method, etc.)

6. Participants must be interested in substituting their normal combustible tobacco
products with ECIG for 4 weeks

7. Willing and able to give informed consent and adhere to visit/protocol schedules

8. Reported method of birth control for at least 3 months prior to enrollment for women
of child bearing potential

9. Read and write in English

HIV-positive patients must meet the following additional inclusion criteria:

10. Currently receive HIV care at the Duke Infectious Diseases Clinic

11. Receiving stable ART treatment (i.e., no ART class changes or changes in dose in
response to poor virological control) for >9 months with viral loads <200 copies/mL

Exclusion Criteria:

1. Alcohol intoxication measured by positive BAL (any detectable level)

2. Acute psychiatric symptoms (e.g. mania, hallucinations) preventing completion of the
study procedures

3. Current use of nicotine replacement or other pharmacotherapy for smoking cessation

4. Positive pregnancy test for women (pregnant women will be referred for smoking
cessation) and/or nursing women

5. Use of other tobacco products (e.g. chew tobacco, snuff) on >10 of the past 30 days
will exclude patients to ensure they are primarily cigarette smokers

6. Use of hand-rolled, roll your own cigarettes

7. Use of marijuana or cigars >2 times/week will be excluded from the study. Subjects
using marijuana ≤2 times/week will be required to refrain for the duration of the
protocol.

8. Positive urine drug screen other than marijuana or currently prescribed medications.

9. Known allergy to propylene glycol or vegetable glycerin (potential constituents of
ECIG)

10. Use of an ECIG for 5 or more within 30 days or any use in the past 7 days

11. Patients with a formal clinical or spirometry diagnosis of co-existing inflammatory
airway conditions of COPD and/or asthma or underlying illnesses that may result in
altered lung function (bronchiectasis, prior surgical lung resection, extensive
cavitary infectious disease, etc.)

12. An ED visit or inpatient admission for a primary respiratory diagnosis or treatment
with antibiotics within 60 days of enrollment

13. History of any systemic or inhaled corticosteroids within 3 months

14. Regular substance abuse or inpatient treatment for these in the past 6 months

15. Poorly controlled concomitant conditions that pose additional procedure risk as
determined by the investigator