Tobacco Studies, Cannabis, E-Cigarettes & Vaping
The harmful effects of tobacco smoke exposure are well documented. Yet research is still necessary to understand the underlying pathophysiological mechanisms and there is a pressing need for new therapeutic agents to treat patients. Scientific evidence is also needed to understand the risks associated with vapour exposure from electronic cigarettes (e-cigarettes) in order to guide the decision-making process for the use of these nicotine delivery devices. The rapid adoption of e-cigarettes, especially amongst the youth, has spurred a rush to fill the knowledge gap pertaining to the safety profile for the users and the environment. Additionally, with increasing legalization of recreational cannabis, there is an increase interest in research into both the pulmonary effects of inhaled cannabis, as well as improving our understanding of the endocannabinoid system.
VERSATILE, PROGRAMMABLE, REPRODUCIBLE
Smoke composition is influenced by a number of technical factors. The constituents of smoke or their concentrations will differ whether the smoke is drawn from side-stream, main-stream or environmental tobacco smoke. It will also vary with the smoke preparation (e.g. cigarette brand, water filtered smoke or hookah, cigars, or e-cigarette liquids) or the puff profile used. Since studies assessing the impact of smoke are typically conducted over a prolonged time period, it is therefore important to consistently and reproducibly introduce the same smoke composition for each experimental session. The inExpose is a versatile, programmable, and compact exposure system that can be configured with smoke generation devices (e.g. cigarette smoking robot, single cigarette chamber, e-cigarettes), or nebulizers to generate a wide range of exposures consistently within and between studies, as well as across laboratories. Using the inExpose system, researchers create accurate and reproducible models of smoke exposure for tobacco, cannabis, and e-cigarette studies using automated generation of vapour, customizable puffing volumes and frequencies.
- A computerized exposure system for animal models to optimize nicotine delivery into the brain through inhalation of electronic cigarette vapors or cigarette smoke. Alasmari, F., et al. Saudi Pharmaceutical Journal, 26(5), 622–628. 2018.
- The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice. Larcombe, A. N., et al. American Journal of Physiology – Lung Cellular and Molecular Physiology, 313(1), L67–L79. 2017.
- The Effect of Electronic-Cigarette Vaping on Cardiac Function and Angiogenesis in Mice. Shi, H., et al. Scientific Reports, 9(1), 4085. 2019.
- Dynamic changes in lung responses after single and repeated exposures to cigarette smoke in mice. Engle, M. L., et al. PLOS ONE, 14(2), e0212866. 2019.
- Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. Hwang JH,. et al. J Mol Med 94(6):667-679. 2016.
- Exposure to electronic cigarette vapors affects pulmonary and systemic expression of circadian molecular clock genes. Lechasseur A., et al. Physiol Rep. 5(19):e13440. 2017.
- Chronic Inhalation of E-Cigarette Vapor Containing Nicotine Disrupts Airway Barrier Function and Induces Systemic Inflammation and Multi-Organ Fibrosis in Mice. Crotty Alexander LE., et al. Am J Physiol Integr Comp Physiol. ajpregu.00270. 2018.
- The expression profile of Claudin family members in the developing mouse lung and expression alterations resulting from exposure to secondhand smoke (SHS). Lewis, J. B., et al. Experimental Lung Research, 44(1), 13–24. 2018.
- Waterpipe Smoke Exposure Triggers Lung Injury and Functional Decline in Mice: Protective Effect of Gum Arabic. Nemmar, A., et al. Oxidative Medicine and Cellular Longevity, 8526083. 2019.
- Proline-Glycine-Proline Peptides Are Critical in the Development of Smoke-Induced Emphysema. Abdul Roda, M., et al. American Journal of Respiratory Cell and Molecular Biology. 2019.
- Inflammatory and oxidative responses induced by exposure to commonly used e-cigarette flavoring chemicals and flavored e-liquids without nicotine. Muthumalage, T., et al. Frontiers in Physiology, 8(JAN). 2018.
- Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice. Yadav, P., et al. Gastroenterology, 153(2), 550–565. 2017.
- Dynamic changes in lung responses after single and repeated exposures to cigarette smoke in mice. Engle, M. L., et al. PLoS ONE, 14(2). 2019.
- Effects of Chronic Inhalation of Electronic Cigarette Vapor Containing Nicotine on Neurotransmitters in the Frontal Cortex and Striatum of C57BL/6 Mice. Alasmari, F., et al. Frontiers in Pharmacology, 10. 2019.
QUANTITATIVE, INTEGRATIVE AND TRANSLATIONAL OUTCOMES
The impact of smoke exposure on the respiratory system can best be captured by evaluating the changes in lung function. These measurements are quantitative and can capture the effect of several disease determinants (e.g. extent and pattern of tissue destruction). The flexiVent system combines a wide selection of lung function measurements within a single device, while offering the sensitivity to capture small but significant changes. Overall and detailed respiratory mechanics, specific lung volumes, pressure-volume or flow-volume loops are examples of measurements that can be used to characterize the respiratory system in tobacco or e-cigarette-related studies, with some outcomes (e.g. FEV, lung volumes) also having a translational value.
- α1-Antitrypsin determines the pattern of emphysema and function in tobacco smoke–exposed mice: parallels with human disease. – Takubo, Yasutaka, et al. Am J Respir Crit Care Med 166.12 (2002): 1596-1603.
- Characterization of biochemical, functional and structural changes in mice respiratory organs chronically exposed to cigarette smoke. – Tsuji, Hiroyuki, et al. Inhalation toxicology 27.7 (2015): 342-353.
- Evaluation of the pulmonary effects of short-term nose-only cigarette smoke exposure in mice. – Nemmar, Abderrahim, et al. Experimental Biology and Medicine 237.12 (2012): 1449-1456.
- Airway surface dehydration aggravates cigarette smoke-induced hallmarks of COPD in mice. – PloS one 10.6 (2015): e0129897.
- Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. – Garcia-Arcos, Itsaso, et al. Thorax (2016).
CHRONIC STUDIES, VENTILATORY PARAMETERS
Smoke-related preclinical studies are often chronic studies involving repeated exposures over several months. During such studies, the harmful effects of smoke exposure on ventilation can be followed in a longitudinal manner using one of the plethysmography techniques (whole body, head-out, double-chamber). Parameters such as breathing frequency, tidal volume, or minute ventilation can be obtained non-invasively with these techniques, both under room air or altered atmospheric (e.g. hypoxia, hypercapnia) conditions. With the appropriate system configuration, the recording and computation of coughing events can also be achieved.
- Effects of cigarette smoke and chronic hypoxia on ventilation in guinea pigs. Clinical significance. – Olea, Elena et al. Adv Exp Med Biol. 2012;758:325-32. doi: 10.1007/978-94-007-4584-1_44.
- Cigarette smoke-induced pulmonary inflammation is TLR4/MyD88 and IL-1R1/MyD88 signaling dependent. – Doz, Emilie, et al. The Journal of Immunology 180.2 (2008): 1169-1178.
- Extracellular matrix defects in aneurysmal fibulin-4 mice predispose to lung emphysema. – PloS one 9.9 (2014): e106054.
- A ferret model of COPD-related chronic bronchitis. – JCI Insight 1.15 (2016): e87536.
CLASSIC, RELEVANT, TRANSLATIONAL
Smoking was established as a common determinant for smoke-related pulmonary and cardiovascular diseases. Exposures to smoke or its constituents can therefore affect airway and/or vascular smooth muscle contractility or relaxation. These effects can be directly addressed using tissue baths, a classic yet relevant and translational approach to study concentration-responses in isolated whole tissue preparations. The technique can be performed on contractile tissues from various sources or species under different conditions to simulate in vivo or clinical conditions (e.g. various oxygen concentrations).
- Structure and Function of Small Airways in Smokers: Relationship between Air Trapping at CT and Airway Inflammation 1. – Berger, Patrick, et al. Radiology 228.1 (2003): 85-94.
- Impairment of Pulmonary Vasoreactivity in Response to Endothelin-1 In Patients With Chronic Obstructive Pulmonary Disease (COPD). – J Vasc Med Surg 3.4 (2015): 213 doi:10.4172/2329-6925.1000213.
- Chronic nicotine treatment enhances vascular smooth muscle relaxation in rats. – Xu, Tian-ying, et al. Acta Pharmacologica Sinica 36.4 (2015): 429-439.
- Measurement of smooth muscle function in the isolated tissue bath applications to pharmacology research. – Jespersen, Brian, et al. J Vis Exp 95 (2015): 52334.
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