E-cigarettes, nicotine, the lung and the brain: multi-level cascading pathophysiology

Abstract

Tobacco smoking is highly addictive and causes respiratory disease, cardiovascular disease and multiple types of cancer. Electronic-cigarettes (e-cigarettes) are non-combustible tobacco alternatives that aerosolize nicotine and flavouring agents in a propylene glycol-vegetable glycerine vehicle. They were originally envisaged as a tobacco cessation aid, but whether or not they help people to quit tobacco use is controversial. In this review, we have compared and contrasted what is known regarding the effects of nicotine on the lungs vs. the effects of nicotine in the brain in the context of addiction. Critically, both combustible tobacco products and e-cigarettes contain nicotine, a highly addictive, plant-derived alkaloid that binds to nicotinic acetylcholine receptors (nAChRs). Nicotine's reinforcing properties are primarily mediated by activation of the brain's mesolimbic reward circuitry and release of the neurotransmitter dopamine that contribute to the development of addiction. Moreover, nicotine addiction drives repeated intake that results in chronic pulmonary exposure to either tobacco smoke or e-cigarettes despite negative respiratory symptoms. Beyond the brain, nAChRs are also highly expressed in peripheral neurons, epithelia and immune cells, where their activation may cause harmful effects. Thus, nicotine, a key ingredient of both conventional and electronic cigarettes, produces neurological effects that drive addiction and may damage the lungs in the process, producing a complex, multilevel pathological state. We conclude that vaping needs to be studied by multi-disciplinary teams that include pulmonary and neurophysiologists as well as behaviourists and addiction specialists to fully understand their impact on human physiology.

Keywords: addiction; airway epithelia; macrophage; pathophysiology; protease.

Figure 1.. Nicotine intake alters lung homeostasis and acts in the brain to promote addiction.

1, Nicotine is inhaled into the lungs where it equals or exceeds 50 μM in the airway surface liquid. 2, Nicotine can activate nAChR in the lung: 2a, Nicotine may inhibit the CFTR Cl⁻ channel, potentially leading to dehydration. 2b, Nicotine stimulates protease release from immune cells, which may lead to (3) lung damage (e.g. bronchiectasis and emphysema). 4, Nicotine is absorbed systemically where it then crosses the blood brain barrier. 5, Nicotine acts on the reward centers in the brain (ventral tegmental area, VTA; nucleus accumbens, NAc) to release dopamine. 6, nAChR densensitization and subsequent upregulation promotes (7) neuroplastic changes associated with craving leading to repeated nicotine uptake and more exposure into the lungs (1).