RISK FROM E-VAPOUR PRODUCTS FOR USERS AND BYSTANDERS Dr Konstantinos Farsalinos Researcher Onassis Cardiac Surgery Center, Greece University of Patras, Greece
COI Past 36 months 1 study funded by non-profit Tennessee Smoke-Free Association (consistency in nicotine delivery to the aerosol of e-cigarettes) 2 studies funded by non-profit AEMSA (nicotine PK studies) Past 48 months 2 unpublished studies on cardiovascular effects of e-cigarettes, hospital reimbursed for the cost of echocardiograms by 2 e-cigarette companies
EXPOSURE OF USERS Propylene glycol Glycerol Nicotine Contaminants - Thermal degradation products
PG Synthetic compound Approved by the FDA for use in food, tobacco, and pharmaceutical products as an inert ingredient Generally Recognized As Safe (GRAS) for direct addition to foods (1982)
PROPYLENE GLYCOL INHALATION
PROPYLENE GLYCOL INHALATION Bacteriostatic/bactericidal effects of PG vapors Protective effect against influenza and common cold
PROPYLENE GLYCOL INHALATION Continuous exposure to an atmosphere saturated with the vapor for 12-18 months showed no deleterious effect on any organ, including the lungs, compared to control animals
PROPYLENE GLYCOL INHALATION No toxic effect was shown in any organ system or blood component Elevation in the number of goblet cells and elevated mucin production in the nasal turbinates (dehydrating effects)
PROPYLENE GLYCOL INHALATION FEV 1 : 103% 102% Small but significant decrease in FEV 1 /FVC Driven by an increase in FVC No lung disease causes an increase in FVC No clinical significance
VG Natural compound, essential for living organisms Approved by the FDA for use in food, tobacco, and pharmaceutical products Generally Recognized As Safe (GRAS) for direct addition to foods (1959) Metabolism through citric acid cycle
VG
CV EFFECTS OF NICOTINE Positive chronotropic and inotropic effects Raises BP, HR, could be arrhythmogenic (ectopic beats) This is a temporary effect Smoking is NOT a risk factor for developing hypertension
SMOKING AND CVD Rigotti & Clair, Eur Heart J 2013
NICOTINE AND CVD Am J Cardiol 2012
NICOTINE AND CVD Woolf et al., Am J Cardiol 2012
NICOTINE AND CVD
NICOTINE AND CVD NRT, the most widely used pharmacotherapy for smoking cessation was associated with an increase in CVD events that was driven by lower risk events, typically tachycardia, a well-known and largely benign effect of NRT Mills et al., Circulation 2013
NICOTINE AND CVD - SNUS
NICOTINE AND CVD - SNUS Smoking 3.53 (2.48-5.03) 8.57 (2.48-30.3) Huhtasaari et al., JACC 1999
NICOTINE AND CVD - SNUS
NICOTINE AND CVD - SNUS Hansson et al., Eur J Epidemiol 2012
NICOTINE AND CVD - SNUS Hansson et al., Eur J Epidemiol 2012
NICOTINE AND CVD - SNUS
NICOTINE AND STROKE - SNUS 130,000 participants All were never-smokers
NICOTINE AND STROKE - SNUS Hanson et al., j Intern Med 2014
NICOTINE AND CVD - SNUS Lee, Harm Red J 2013
NICOTINE AND FATAL MI Acute myocardial infarction + Acute sympathetic activation = Arrhythmias Exercise causes acute sympathetic activation Contraindicated in acute MI
FLAVORINGS Natural Nature-identical (synthetically produced) Artificial GRAS status for ingestion (FEMA/FDA, EFSA) Not evaluated for safety when inhaled Does not necessarily mean they are harmful (or harmless)
DIACETYL ACETYL PROPIONYL Diketones, safe for ingestion but reasons for concern regarding inhalation Bronchiolitis obliterans, non-specific lung dysfunction (reduced FEV 1 )
THERMAL DEGRADATION Oxidation of PG and VG to form aldehydes (mainly formaldehyde, acetaldehyde) Gillman et al., Regul Toxicol Pharmacol 2015
THERMAL DEGRADATION Oxidation of PG and VG to form aldehydes (mainly formaldehyde, acetaldehyde) Farsalinos et al., Addiction 2015
THERMAL DEGRADATION Dry puffs will increase aldehyde formation Flavors? Khlystov et al., Environm Res Technol 2016
ug/g liquid THERMAL DEGRADATION 12000 Coffee flavor in both cases (different brands) 10000 9856 8000 7000 6000 4000 2000 0 380 Khlystov (EVOD, 10.7 W, no dry puff) Farsalinos (CE4, 7 W, no dry puff) Farsalinos (CE4, 8 W, dry puff) Farsalinos (CE4, 11.4 W, dry puff) 2339
THERMAL DEGRADATION 1200 1000 1000 800 600 400 200 0 Khlystov-cigalike-tobacco flavor 70 Geiss-3rd gen-15w-tobacco
ACROLEIN?
ACROLEIN? Hect SS, et al. Nicotine Tob Res 2015 McRobbie et al. Cancer Prev Res 2015
PASSIVE EXPOSURE TO NICOTINE Czogala et al., Nicotine Tob Res 2013
PASSIVE EXPOSURE TO NICOTINE
PASSIVE EXPOSURE TO NICOTINE
PASSIVE EXPOSURE TO NICOTINE 160 140 No biological effect 146 120 100 80 60 LOAEL (increase in heart rate 260 ug nicotine IV 25 ug nicotine/d 40 20 0 0.24 Passive vaping (Balbe, 2016) Smoking (Balbe, 2009)
PM SIZE AND MASS Particulate matter (PM) associated with cardiovascular and respiratory disease Not all is the same PM of environmental pollution/smoking PM from boiling water (the smallest-size particles) (Ogulei et al., Indoor Air 2006;16:204-215) PM from e-cigarettes microdroplets of PG, VG, nicotine What matters is composition If composition is harmful, low PM size and high PM mass will cause harm
FORMALDEHYDE Schripp et al., Indoor Air 2013
METAL EMISSIONS
WHAT IS THE VAPER EXHALING? Long, IJERPH 2014
CONCLUSIONS E-cigarette users Probably not harmless Level of risk by far lower compared to smoking Perfect harm reduction approach, but not for general use by non-smokers Passive exposure Main exposure to PG,VG and extremely low nicotine No reason for concern No harm ever seen from passive use Abuse of precautionary principle to apply universal restrictions-bans Will expose vapers to harmful effects of passive smoking will provide misleading message to smokers that e-cigarettes are of similar risk to smoking