Reduction of Exposure, Inflammation, and Oxidative Stress Following at Least 2 Years of Switching to THS Use Compared to Cigarette Smoking

Inclusion Criteria: * Subject is able to understand the information provided in the main ICF and has signed the main ICF. * Subject is 30-60 years old. * Subject is healthy based on ECG, spirometry, vital signs, physical examination, medical history and Investigator's assessment. Cigarette smokers: * Has smoked ≥ 10 cigarettes/day on average (no brand restriction) over the past 2 years prior to screening. * Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 10 years. * Has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past 2 years prior to screening. * Smoking status will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (≥ 10 ppm (1)). THS users: * Has used ≥ 10 HeatSticks/day on average over the past 2 years prior to screening. * Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to switching to THS. * Has smoked \< 30 cigarettes/month and used other tobacco products or e-cigarettes \< daily over the past 2 years prior to screening. * Product use will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (\< 10 ppm). Former cigarette smokers: * Has not smoked cigarettes or used any tobacco or nicotine-containing products on a daily basis over the past 2 years prior to screening. * Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to stopping smoking. * Smoking status will be verified by urinary cotinine test (\< 100 ng/mL) and CO breath test (\< 10 ppm). Exclusion Criteria: * As per the judgment of the Investigator, the subject cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason). The Investigator should specifically evaluate the subject's eligibility considering COVID-19 risk factors and local situation. * The subject is legally incompetent or physically/mentally incapable of giving consent (e.g., emergency situation, under guardianship, in a social or sanitary establishment, prisoner or involuntarily incarcerated). * The subject has/had clinically relevant diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease) or conditions that in the opinion of the investigator would jeopardize the safety of the subject or affect the validity of the study results. * The subject has abnormal findings on physical examination, ECG, vital signs, spirometry or in the medical history, deemed clinically significant by investigators. * The subject has/had within 30 days prior to screening a body temperature \>37.5°C or an acute illness (e.g., upper-respiratory-tract infection, viral infection, etc.…) or the subject is confirmed or suspected active COVID-19 infection (based on the signs and symptoms observed at the time of assessment) at screening. * The subject has used any prescribed or over-the-counter systemic medication with an impact on WBC or 8-epi-PGF2α within 5 half-lives of the medication prior to enrollment in the study (please refer to Appendix B). * Subject has high blood pressure (hypertension), defined as \> 139 mmHg systolic and/or \> 89 mmHg diastolic or is currently treated with medication controlling high blood pressure. * The subject has (FEV1/FVC) \< 0.7 and FEV1 \< 80% predicted value at post-bronchodilator (BD) spirometry. * The subject has (FEV1/FVC) \< 0.75 (pre-BD) and reversibility in FEV1 (that is both \> 12% and \> 200 mL from pre- to post-BD values). * The subject has a history of allergic reactions to salbutamol. * The subject has a body mass index (BMI) \< 18.5 or ≥ 30 kg/m2. * The subject has positive alcohol and/or drug screening test results. * The subject has donated or received whole blood or blood products within 3 months prior to V1. * The subject has been previously screened for this study. * The subject is a current or former employee of the tobacco or e-cigarettes industry or of their first-degree relatives (parent, sibling, and child). * The subject is an employee of the investigational site or any other parties involved in the study or of their first-degree relatives (parent, sibling, and child). * The subject has participated in a clinical study within 3 months prior to V1. * For women only: the subject is pregnant (does have a positive pregnancy test) or breast-feeding.