Please select the eligibility criteria that correspond to the clinical trial below.
Title: Vascular Effects of Regular Cigarettes Versus electronIc Cigarette Use
Brief Summary: The purpose of this study is to assess the effects of electronic cigarettes-nicotine and electronic cigarette-nicotine free on endothelial function as compared to traditional cigarettes. Due to ethical reasons, we cannot fully randomise all particpants to the three arms.

Participants who wish to quit smoking will be randomized to

1. Switch to electronic cigarettes containing nicotine plus flavor
2. Switch to electronic cigarettes containing flavor alone Those who do not wish to quit smoking will continue on the Tobacco Cigarette arm Treatment period will be 28 days


Options:
A: Inclusion Criteria:

* Age 18+
* Smoke an average of at least five cigarettes per day for at least 1 year
* Breath CO levels \> 8 ppm (if ≤ 8 ppm, then NicAlert Strip \> 2)

Exclusion Criteria:

* Intention to quit smoking in the next 30 days
* Currently seeking treatment for smoking cessation
* Currently using nicotine replacement therapies or other pharmacotherapies as cessation aid (intermittent use acceptable)
* A quit attempt in the past 30 days resulting in greater than 3 days of abstinence
* Using other tobacco products more than 9 days in the past 30 days
* Significant unstable medical conditions (Any significant change in a serious medical condition occurring during the past 3 months including, cardiovascular disease, COPD, and cancer, as determined by the licensed medical professional at each site)
* Significant unstable psychiatric conditions (Any significant change in psychiatric symptoms during the past 3 months as determined by the licensed medical professional at each site)
* Schizophrenia and schizoaffective disorder
* Psychiatric medication changes in the past 3 months
* Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP

  1. Marijuana will be tested for but will not be an exclusionary criterion.
  2. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded.
  3. Participants failing the toxicology screen will be allowed to re-screen once.
* Blood alcohol level \> 0.01

  a. Participants failing the blood alcohol screen will be allowed to re-screen once.
* Binge drinking alcohol (more than 9 days in the past 30 days, 4/5 in a 2 hour period(female/male))
* Pregnant or breastfeeding
* Smoking 'roll your own cigarettes' exclusively
* Currently taking anticonvulsant medication
* CO reading \>80 ppm
* Systolic BP greater than or equal to 160

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Diastolic BP greater than or equal to 100

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Systolic BP below 90

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Diastolic BP below 50

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Heart rate greater than or equal to 115bpm

  a. Participants failing for heart rate will be allowed to re-screen once.
* Heart rate lower than 45bpm

  a. Participants failing for heart rate will be allowed to re-screen once.
* Indicating any suicidal ideation in the past month or suicide attempts in the past 10 years
* Inability to independently read and comprehend the consent form and other written study materials and measures
* Having participated in a research study during the past three months in which the participant:

  1. Smoked a cigarette that was not his/her usual brand cigarette for more than one day
  2. Used any tobacco products beyond normal use for more than one day
  3. Used any nicotine replacement products or smoking cessation medications for more than one day
B: Inclusion Criteria:

* Smokers volunteers, minimum age 18 years

Exclusion Criteria:

* no history of acute or chronic organic, metabolic and inflammatory diseases;
* no fever and infections in the last 3 months;
* no history of cardiovascular pathological symptoms;
* no allergies;
* none of the participants took vitamin E, other antioxidant supplements or other drugs potentially affecting oxidative stress or FMD
* women were not menstruating when the experiment was performed.
C: Inclusion Criteria:

* Age 21-65
* Smoke \>9 cigarettes per day for at least 1 year
* Smoke regular filtered cigarettes or machine-rolled cigarettes with a filter
* CO measurement \>9 ppm at baseline
* No serious quit attempt in the prior 1 month. 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 1 month as an indication of treatment seeking.
* Not planning to quit in the next 6 months
* Interested in reducing cigarette consumption
* Willing to attend visits weekly and monthly over a 9-month period (not planning to move, not planning extended vacation, no planned surgeries)
* Read and write in English
* Able to understand and consent

Exclusion Criteria:

* Pregnant and/or nursing women
* Unstable or significant medical condition in the past 12 months (Recent heart attack or some other heart conditions, stroke, severe angina including high blood pressure if systolic \>159 or diastolic \>99 observed during screening).
* Immune system disorders, respiratory diseases (exacerbations of asthma or COPD, require oxygen, require oral prednisone), kidney (dialysis) or liver diseases (cirrhosis), or any medical disorder/medication that may affect participant safety or biomarker data.
* Use of any non-cigarette nicotine delivery product (pipe, cigar, dip, chew, snus, hookah, ECIGs, strips, sticks) in the past 7 days
* Uncontrolled mental illness or substance abuse or inpatient treatment for these in the past 6 months
* History of difficulty providing or unwilling to provide blood samples (fainting, poor veins, anxiety)
* No surgery requiring general anesthesia in the past 6 weeks
* Use of an ECIG for 5 or more days in the past 28 days or any use in the past 7 days
* Use of marijuana or any illicit drug/prescription drugs for non-medical use daily/almost daily, or weekly in the past 3 months per NIDA Quick Screen
* Use of hand-rolled, roll your own cigarettes
* Known allergy to propylene glycol or vegetable glycerin
* Other member of household is currently participating/participated in the study
D: Inclusion Criteria:

* Aged 18 years and over
* Currently smoking ≥15 full strength tobacco cigarettes per day for at least 2 years, or roll-up tobacco equivalent (cigar or pipe smokers not included).
* Willing to stop tobacco cigarettes for period of study if required
* Willing not to use electronic cigarettes if required
* Able to give informed consent

Exclusion Criteria:

* Pregnant or lactating.
* Women of childbearing potential who do not abstain from sex or use effective contraception.
* On current prescribed medication for cardiovascular disease.
* History of cardiovascular disease (excluding hypertension), diabetes, active malignance or chronic renal disease.
* Nut allergy
* Participation in another clinical trial (other than observational trials and registries) with an investigational product and/or intervention within 30 days before visit 1.

Answer: D