Please select the eligibility criteria that correspond to the clinical trial below.
Title: Benefits of Tobacco Free Cigarette Among Heavy Smokers Undergoing a Lung Cancer Screening Program: a Randomized Controlled Study
Brief Summary: Background. Smoking is considered a global public health problem. For this reason, the smoking dependence was called by experts as a global epidemic.

Over the past three years, this electronic devices (Tobacco Free Cigarettes, or TFC) has been an important expansion in many countries. Nevertheless, there is poor evidence that TFC are beneficial for smoking cessation. In particular, even though it has been proved that the nicotine replacement devices helps many individuals to give up smoking and to tolerate the withdrawal symptoms, it is still unclear their long-term effect. Hence, it must be tested its contribution in tobacco reduction. This protocol in particularly innovative, since it aims to test the efficacy of electronic devices in a screening program (the lung cancer prevention program COSMOS II at the IEO), where tobacco reduction is strictly needed in order to lower individual's risk.

Methods and Design. This experimental protocol has been designed with the main aim to investigate the role of Tobacco Free Cigarettes (TFC), also called e-cigarettes, in helping smokers to improve their lung health and to quit or reduce tobacco consuming. In particular, the investigators aim at investigating clinical (physical symptoms, with particular focus on breathing quality and difficulties), the behavioral (number of tobacco cigarettes smoked), and psychological (wellbeing, mood and quality of life) effects of shifting to TFC.

The investigators will also analyze, as a secondary aim, the psychological and lifestyle component of smokers involved in order to fine correlation data that might be used to compute a predictor index able to suggest the probability of success, with respect to the reduction of tobacco consuming, of the use of a TFC and to maintain the abstinence. The study will be organized as a nested randomized controlled study with two arms: one experimental group and one control group. The study will be nested in the screening program for lung cancer, where subjects will be recruited.

All subjects will be entered in a psycho-cognitive low-intensity counseling program (6 months), but in the experimental group a TFC (with or without nicotine) will be used as replacement device for three months, while in the control group only low-intensity counseling will be provided. Furthermore, a low-cost non-invasive electronic device (the FitBit activity tracker) will be used in order to monitor behavioral (lifestyle), sleep quality and physical activities.


Options:
A: 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.
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:

* Residing in the newly merged Leeds South \& East, Leeds West or Leeds North CCG
* Registered as a current or ex-smoker in a General Practice participating in YLST
* Have attended for a 'Lung Health Check' and agreed to see the SCP as part of YLST
* Smoked within the last month or have exhaled CO reading of 6ppm or above.
* Have capacity to provide informed consent.
D: Inclusion Criteria:

1. Subjects involved in the early lung cancer detection program (Cosmos II) of the European Institute of Oncology.
2. Subjects should have smoked at least 10 cigarettes a day for the past 10 years
3. Subjects that would like to reduce tobacco smoking but are not willing to be followed by a smoking center
4. To have an high motivational scoring (more than 10 points to the motivation questionnaire);
5. Signed informed consent

Exclusion Criteria:

1. symptomatic severe cardiovascular disease
2. symptomatic severe respiratory disease
3. regular psychotropic medication use
4. current or past history of alcohol abuse
5. use of smokeless tobacco or nicotine replacement therapy
6. pregnancy or breastfeeding.
7. Subjects involved in other antismoking program in the current year.

Answer: D