Acute Vascular Effects of E-cigarette Use
Condition: Healthy
Study type: Interventional

Summary: 
      Tobacco use harms nearly every organ in the body and has been linked to ischemic heart
      disease, chronic obstructive pulmonary disease, stroke, respiratory illness, lung cancer and
      other cancers. The World Health Organization estimates that 6 million people worldwide lose
      their lives due to tobacco use yearly, making cigarette smoking one of the leading single
      causes of preventable death and morbidity.

      As this knowledge becomes more common and wide-spread the sales of cigarettes has seen a
      decrease in recent years. On account of this, the electronic cigarette (e-cigarette) has been
      introduced to the market as an alternative to traditional cigarette smoking. Electronic
      cigarettes, also known as e-cigarettes or e-cigs, are delivery devices which heat a base
      liquid, to which nicotine and flavorings can be added, into vapor which is then inhaled
      ("vaping"). E-cigarettes have been aggressively marketed as a cheaper, healthier, cleaner
      alternative to smoking in both advertising and media outlets, primarily targeting
      adolescents.

      Despite growing e-cigarette use, scientific data on health effects are insufficient in some
      respects and completely lacking in others. However, the investigators have recently shown
      that cigarette smoking, as well as e-cigarette inhalation, both cause an acute increase of
      endothelial progenitor cells (EPCs) in the blood of healthy volunteers, suggesting vascular
      injury, inflammation and a negative impact on hemostasis.

      Therefore, using well validated methods, including forearm plethysmography, biomarkers in
      blood, arterial stiffness measurements and microcirculation assessment (GlycoCheck), the
      investigators aim to further investigate the effects of e-cigarette inhalation on the
      vascular system. These measurements will be performed before and after healthy subjects
      inhale vapor from a e-cigarette on two separate occasions, with and without nicotine in a
      double-blinded, randomized protocol.
    

Detailed description: 
      According to the World Health Organization cigarette smoking is today one of the leading
      single causes of preventable death and morbidity. It is estimated that 7 million people
      worldwide lose their lives due to tobacco use yearly. On average, cigarette smokers are
      estimated to die 10 years earlier than non-smokers. Ischemic heart disease, chronic
      obstructive pulmonary disease, stroke, respiratory illness, lung cancer and other cancers
      have all been linked to tobacco use. Cigarette smoking has known detrimental effects on the
      blood vessels and both active as well as passive use causes endothelial dysfunction, one of
      the earliest signs of atherosclerosis. The investigators have recently shown that cigarette
      smoking, as well as e-cigarette inhalation, both cause an acute increase of endothelial
      progenitor cells (EPCs) in the blood of healthy volunteers, suggesting vascular injury,
      inflammation and negative impact on hemostasis.

      In recent years the electronic cigarette has been introduced to the market as an alternative
      to traditional cigarette smoking. Electronic cigarettes, also known as e-cigarettes or
      e-cigs, are nicotine delivery devices, which heat a base liquid, to which nicotine and
      flavorings can be added, into vapor which is then inhaled ("vaping"). Many of the first
      generation e-cigs emulate conventional cigarettes in appearance, though in second and third
      generation devices many shapes and sizes exist, varying from one time devices roughly the
      size of a conventional cigarette to much larger atomizers, designed to be refilled.
      E-cigarettes have been aggressively marketed as a cheaper, healthier, cleaner alternative to
      smoking in both advertising and media outlets, primarily targeting women and adolescents.

      With declining cigarette sales in the western world, tobacco companies show a great interest
      in this expanding and highly profitable market, buying already established e-cigarette
      companies. In February 2014, the European Commission revised the tobacco products directive
      allowing the trade of e-cigarettes in the European Union. Despite growing e-cigarette use,
      scientific data on health effects are insufficient in some respects and completely lacking in
      others. With limited knowledge of e-cigarette vaping health effects in humans it has been
      challenging for governments and health officials to give advice and regulate the use of this
      novel product. Therefore, using the 'gold standard' method for assessing vascular function,
      forearm plethysmography, the investigators aim to investigate the effects of e-cigarette
      inhalation on the cardiovascular system.

      Healthy volunteers will attend on three occasions. The initial visit will be a health
      assessment in order for inclusion into the study, when ECG, spirometry and blood sampling
      (max 30 ml of blood) will be performed.

      All subjects will inhale vapor from a nicotine-containing e-cigarette for 30 minutes in a
      specially prepared room with adequate ventilation. In a randomized cross-over fashion,
      subjects will also 'smoke' e-cigarette without nicotine on separate occasions. These two
      occasions will be separated by at least one week.

      Subjects will rest for 20 minutes prior to vaping. Arterial stiffness, blood pressure,
      microcirculation assessment (GlycoCheck) and pulse will be measured before and for 60 minutes
      following vaping. Blood samples will be drawn before, as well as at several time points
      throughout the study protocol.

      Forearm blood flow will be measured using venous occlusion plethysmography in both forearms
      before and during the intra-arterial infusion of acetylcholine (5, 10 & 20 µg/min; an
      endothelial-dependent, NO- dependent vasodilator), glyceryl trinitrate (4, 8 & 16 nmol/min;
      an endothelial-independent, NO-dependent vasodilator), and bradykinin (100, 300 & 1000
      pmol/min; an endothelial-dependent vasodilator that stimulates release of tissue plasminogen
      activator (t-PA)).
    

Intervention name(s): E-cigarette vapor containing nicotine; E-cigarette vapor, nicotine free
Intervention type(s): Other; Other
Intervention description(s): A fourth generation e-cigarette device will be used with pre-determined temperature, voltage and wattage settings, and pre-mixed e-solution containing nicotine.; A fourth generation e-cigarette device will be used with pre-determined temperature, voltage and wattage settings, and pre-mixed nicotine free e-solution.
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Nicotine; Electronic cigarette; E-cigarrette; Forearm Plethysmography