Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects on Oxidative Stress and Platelet Activation of Traditional Cigarettes, E-cigarettes and IQOS Cigarettes: A Randomized in Vivo Study.
Brief Summary: Electronic cigarettes (E-cigarettes) and new heat-not-burn tobacco products such as IQOS®, an electronic device that heats a cigarette-like stick without combustion, are a modern and technological surrogate of traditional tobacco cigarettes (T-cigarettes), that are entering in the commercial market. While the negative effects of the traditional cigarette are well known, little data are reported in scientific literature on the risks on the health by these new smoking devices. Endothelial dysfunction evaluated by flow-mediated dilatation (FMD), oxidative stress and platelet activation have been recognized as a hallmark of preclinical systemic atherosclerosis and as a useful marker to stratify the risk of cardiovascular disease in patients at risk or with established clinically significant atherosclerosis. Since no data are reported about the effects of these new smoking device on oxidative stress, platelet activation and FMD, the investigators designed a human study assessing if these new smoking devices have effects on healthy smokers.


Options:
A: Inclusion Criteria:

* healthy smokers
* unwilling to quit
* age 18-60 years
* smoking ≥ 15 cig/day for at least 5 years
* exhaled CO level of ≥ 15 ppm
* FTND ≥ 5

Exclusion Criteria:

* alcohol and illicit drug use
* breastfeeding or pregnancy
* major depression or other psychiatric conditions
* previous experience with ENDD
* recent myocardial infarction
* angina pectoris
* high blood pressure (BP\>140mm Hg systolic and/or 90mmHg diastolic)
* diabetes mellitus
* severe allergies
* poorly controlled asthma or other airways diseases
B: Inclusion Criteria:

Participants will be required to satisfy all of the following criteria at the screening visit, unless otherwise stated:

• Participants will be: 1.1. over 23 years of age

• T2DM Patients will have: 2.1. body mass index (BMI) between 17.6 and 34.5 kg/m2, inclusive 2.2. body weight exceeding 50 kg (males) or 40 kg (females) 2.3 6.0\<HbA1C\<12 3.2. completion of proforma (CRF) 3.3. lab assessment as outlined in the CRF

* Participants will be willing to refrain from eating/drinking prior to screening and Check-in at each study visit.
* Participants will be regular smokers of at least 10 cigarettes/day (max 30 cigarette/day)
* Participants will have smoked for at least five consecutive years prior to screening.
* Participants must have a saliva cotinine level \> 10 ng/mL or an exhaled breath CO (eCO) level \> 7 ppm at screening.
* Participants in Arm A who continue to smoke will be willing to use their own brand/type cigarettes.
* Participants in Arms B will be willing to use the study products (THP product or e-cigarette) provided to them during the study.

Exclusion Criteria:

Participants will be excluded at the screening visit based on the following criteria:

* Female participants who are pregnant or breastfeeding. This will be confirmed at screening and at visit 1. Any female subject who becomes pregnant during this study will be withdrawn.
* Participants with a history of recent acute decompensation of their disease requiring treatment within 4 weeks prior to visit 1.
* Participants who have a significant history of alcoholism or drug/chemical abuse within 24 months prior to screening, as determined by the investigator.
* Participants who are still participating in another clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to first product use.
* Participants who have, or who have a history of, any clinically-significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, haematological or other major disorder that, in the opinion of the investigator or their appropriately qualified designee, would jeopardise the safety of the subject or impact on the validity of the study results.
* Participants who regularly use any nicotine (e.g. e-cigarettes, NRT) or tobacco product (e.g. HTPs, oral smokeless) other than their own cigarettes within 14 days of screening.

At screening and prior to enrolment, all patients will be offered a locally available free smoking cessation program as per local guidelines. Those who express the intention of booking for the cessation program together with those who, at screening, are planning to quit smoking in the next 6 months, will not be recruited in the study. Patients taking part in the study will be informed that they are free to quit smoking and withdraw from the study at any time. Any subject who decides to quit smoking will be directed to local stop smoking services.

Withdrawal Criteria:

Patients may be withdrawn from the study prematurely for the following reasons:

1. subject experiences a severe adverse event (SAE). The appropriate SAE electronic Case Report Form (eCRF) page must be completed.
2. If any deviations occur during the conduct of the study, which cannot be corrected. All protocol deviations will be fully documented and considered for their effect on study objectives. Deviations that could lead to subject discontinuation from the study include:

   * deviations which could affect subject's safety (e.g. illness requiring treatment\[s\]) which in the clinical judgement of the investigator might invalidate the study by interfering with the allocated test product or the willingness of the subject to comply with the study activities.
   * deviations involving the use of any nicotine/tobacco products other than the intended conventional cigarettes (in Arm A) or (in Arm B).
3. If the subject is uncooperative, including non-attendance. In these cases, efforts should have been made by the investigator to ascertain the reason and to ensure the subject's attendance as soon as possible.
4. Subject's personal request: the subject could decide, at any moment of the study, to stop his/her participation.
5. Female participant becoming pregnant.
C: Inclusion Criteria:

* \> 21 years of age
* Smoked cigarettes on \> 25 of past 30 days
* Smoked \> 5 cigarettes per day on days smoked
* Smoked cigarettes \> 6 months
* Carbon monoxide \> 5 PPM at baseline
* Hispanic/Latino or African American/Black
* Fluent in English or Spanish
* Willing to switch from smoking cigarettes to ECs for 6 weeks
* Regular access to telephone
* Transportation to attend appointments (KC Only)

Exclusion Criteria:

* Primary use of other tobacco products or equal use of cigarettes and other tobacco products
* Electronic cigarette use on \> 4 of the past 30 days
* Currently in a smoking cessation program or another clinical trial
* Use of nicotine replacement therapy or medication which aids smoking cessation in the past 30 days
* Hospitalization for a psychiatric issue in the past 30 days
* Heart-related event in the past 30 days. Examples include heart attack, stroke, severe angina (i.e. chest pain), ischemic heart disease, and vascular disease
* Uncontrolled blood pressure at baseline
* Planning to move out of San Diego or Kansas City in the next 6 weeks
* Another person in the household enrolled in the study
* Women: pregnant, breastfeeding, or planning to become pregnant in the next six months
* Unstable mental status or health status
D: 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.

Answer: D