Waterpipe tobacco smoke toxicant exposure and effects Alan Shihadeh American University of Beirut 1st International Conference on WTS October 20-23, 2013 Abu Dhabi
Waterpipe toxicants & health effects Molecule Particle Cell Animal Human individual Population health • Does the smoke contain toxicants? • particle size • chemistry • biological activity inhaled sidestream(SS) SS + EMS Does the user absorb toxicants? biomarkers in: blood, breath, urine Does waterpipe smoking emit toxicants? exhaled mainstream (EMS) exhaled absorbed • What happens to the user? • acute physiological effects • BP, HR, inflammatory responses, lung function… • What happened to the smoker? • long term mortality & morbidity http://firefighterparamedicstories.blogspot.com/2011_10_01_archive.html
Narghile waterpipe Photo credit: internet, source unknown
Narghile waterpipe Differences with cigarette tobacco burn not self-sustaining charcoal needed Tobacco temperature < 500 C (Cig < 900 C) “molasses” flavorings order of magnitude higher flow rates/puff volumes long flow path with bubbler/humidifier (produces cool “smooth” smoke)
Tobacco smoke constituents N2, O2, CO2 CO Gas phase ~ 90% wt (invisible) water vapor C2-C6 hydrocarbons, aldehydes, nitriles … Smoke aerosol condensed water Particle phase 10-1000 nm (visible) nicotine 4000+ compounds PAH, nitrosamines, metals,… contains most important carcinogens “tar” Illustration from: N. deNevers Pollution Control
The “Hoffmann List“ of probable causative agents in cigarette smoke-related disorders Hoffmann et al, 2001; Hecht 1997
The “Hoffmann List“ of probable causative agents in cigarette smoke-related disorders *Hoffmann et al, 2001; Hecht 1997
Particle size & lung dosimetry “Ultrafine particles” Hinds, Aerosol Technology (1999)
Human hair Tobacco smoke particle (100-200 nm)
Do waterpipes emit toxicants? What is in the smoke? 1) Find out how people smoke waterpipes 2) Program a robot to smoke the same way 3) Analyze the smoke for toxicants
Find out how people smoke Shihadeh, Antonius, Azar, BRIMC,2005 • Average puff topography • Volume • Duration • Frequency • Number Puff topography record
Results Field study of 52 café smokers in Beirut mean age 21 years, 14 f/38 m A. Shihadeh et al, Biochemistry, Pharmacology, and Behavior, 79(1),75-82, 2004
“Beirut method” – a standard waterpipe smoking machine protocol for generating WTS • puff regimen • volume • duration • frequency • number • Ma’ssel quantity • charcoal type and application regimen • head preparation the “Beirut method” 171 puffs, 530 ml, 2.6 s duration, 17 s IPI 10 g ma’asseltobacco mixture load 1 easy-light charcoal disk + 0.5 added at 105th puff 18-hole aluminum perforation pattern
Program smoking robot & sample/analyze smoke Shihadeh & Azar, JAM, 2006
Waterpipe smoke particles are biologically active • In vitro effects of WTS on HEACs • Oxidative stress • Inflammation • Cell cycle arrest • Impaired vasodialation • Impaired angiogenesis • Plausible cellular mechanism for vascular diseases Rammah et al, 2013 Toxicology Letters Volume 219, Issue 2 2013 133 - 142
Impaired angiogenesis Capillary tube formation of untreated and treated HAEC cells (mg/ml) WSC. Rammah et al, 2013 Toxicology Letters Volume 219, Issue 2 2013 133 - 142
Waterpipe smoke particles are biologically active Effects on lung epithelial (A549) and endothelial cells and signaling mechanisms Plausible cellular mechanism for COPD Hoechst staining of cells 72 hours post-treatment with WSC. Pictures were taken using a 40x oil immersion lens. Rammah et al, 2012 Toxicology Letters
Does the user inhale toxicants? YES. Based on the Beirut Method: • During a single WP use session the user inhales a large dose of toxicants known to cause tobacco-related diseases • WTS particle size distribution is similar to cigarette smoke • WTS damages and interferes with repair mechanisms of lung and vascular cells in culture Q. Does the Beirut Method provide a reasonable facsimile of real smoke?
Charcoal(!) More charcoal than ma’ssel is consumed during a typical use session Users continually “tune” it charcoal electrical heater temperature vs time Monzer, B., Sepetdjian, E., Saliba, N. and Shihadeh, A. Charcoal combustion as a source of CO and carcinogenic PAH in mainstream narghile waterpipe smok, Food and Chemical Toxicology, 2008
REALTIME sampling in the natural environment Katurji et al, InhTox, 2010
c) nicotine:tar a) nicotine d) CO b) “tar” How does Beirut Method smoke compare to smoke made by people? Beirut Method Nicotine “Tar” Volume (l) Volume (l) Nicotine:Tar CO “tar” (mg) Volume (l) Katurji et al, InhTox, 2010
Do waterpipe users absorb toxicants? What is in the smoker? Measure toxicant levels in blood, breath, or urine. Studies: placebo control, cigarette comparison, observational. Contains “tar”, CO, Nicotine,PAHs, aldehydes….
CO and nicotine in blood 14 5 Plasma nicotine (N=31) Carboxyhemoglobin (N=31) 12 4 10 3 8 ng/ml Percent 6 2 4 1 2 0 0 0 5 15 30 45 0 5 15 30 45 Time relative to smoking onset Time relative to smoking onset Clinical setting, one 45 min WP session Eissenberg & Shihadeh, American Journal of Preventive Medicine, 37, 518-523, 2009.
CO and nicotine in blood: compared to cigarettes 14 5 Carboxyhemoglobin (N=31) Plasma nicotine (N=31) * * 12 4 Waterpipe * 10 * Cigarette 3 8 ng/ml Percent * 6 2 4 1 2 0 0 0 5 15 30 45 0 5 15 30 45 Time relative to smoking onset Time relative to smoking onset Eissenberg & Shihadeh, American Journal of Preventive Medicine, 37, 518-523, 2009.
CO and nicotine exposure over 24 hours Plasma nicotine (n=13) Exhaled breath CO (n=13) • Hospital setting, cross-over design, N=13 dual users • All day ad libitimcigarette smoking (11 cpd mean) versus 3 WTS use sessions • Measurements on day 4 of 4-day protocol. Jacob et al, 2013. Cancer Epidemiol Biomarkers Prev 2013;22:765-772.
Carcinogen exposure over 24 hours Urinary NNAL (TSNA biomarker) Urinary 1-HOP (PAH biomarker) • Hospital setting, cross-over design, N=13 dual users • All day ad libitimcigarette smoking (11 cpd mean) versus 3 WTS use sessions • Measurements on day 4 of 4-day protocol. Jacob et al, 2013. Cancer Epidemiol Biomarkers Prev 2013;22:765-772.
Carcinogens in populations of smokers Urine samples collected from population in Aleppo. Mean cigarette use 27 cigs per day, mean WTS 2 per day. Al Ali R, et al. 2013 Tob Control doi:10.1136/
Do waterpipe users absorb toxicants? • YES! • Clinical, hospital, natural environment findings consistent with one another • Generally consistent with what we know about toxicants in smoke: • CO WP >> cig • PAH WP > cig • TSNA WP < cig • Nicotine WP ~ cig
Delivered nicotine is physiologically active sympathetic activation reduced complexity Cobb et al., Inhalation Toxicology 2012
WP smoke suppresses “Urge to smoke” after 24 hour abstinence Rastam et al., 2011
WP smoke compromises cardiac autonomic regulation in human participants (with or without nicotine!) baseline end 15 min baseline end 15 min sympathetic activation reduced complexity Cobb et al., Inhalation Toxicology 2012
WP smoke inhalation induces inflammation and oxidative stress in mice Inflammatory markers Oxidative stress Khabour et al 2012 InhTox
WP smoke inhalation associated with: • Genotoxicity (sister chromatid exchanges): WTS > CS > nonsmokers (Khabour et al, 2011) • Reduction in exercise capacity : VO2 1.86 vs. 1.7 l/min, pre- post (Hawari et al., 2013) • Reduction in lung function (Hakim et al., 2011; Mohammad et al., 2008; Koseoglu et al., 2006; Kiter et al., 2000; Aydin et al. 2004; Al Mutairi et al., 2006, Al Fayez et al., 1988): “WPS negatively affects lung function and may be as harmful as cigarette smoking. WPS, therefore, is likely to be a cause of COPD.” – Raad et al., 2011
What happened to the smoker? Waked, Khayat, Salameh, 2012
What happened to the smoker? (Jawad et al., 2013 based on Akl et al., 2010) “A wide range of diseases have been associated with WTS, but research in this area is relatively underdeveloped and a better evidence base is needed.” - Akl et al., 2010
Does waterpipe smoking emit toxicants into the environment? • Does the user inhale toxicants? • particle size • chemistry • biological activity inhaled sidestream(SS) SS + EMS Does the user absorb toxicants? biomarkers in: blood, breath, urine Does waterpipe smoking emit toxicants? exhaled mainstream (EMS) exhaled absorbed • What happens to the user? • acute physiological effects • BP, HR, inflammatory responses, lung function… • What happened to the smoker? • long term mortality & morbidity http://firefighterparamedicstories.blogspot.com/2011_10_01_archive.html
Do waterpipe smoking emit toxicants? • chamber based studies • observational studies of cafés
Chamber study Daher et. al, Atmospheric Environment, 44, 8-14, 2009.
Waterpipe emits more nanoparticles Particle concentration (particles/cm3) Daher et. al, Atmospheric Environment, 44, 8-14, 2009.
WP emits more of everything measured Daher et. al, Atmospheric Environment, 44, 8-14, 2009.
What about per smoker-hour? • Waterpipe smokers release equivalent of 2-10 cigarette smokers per hour of smoking Daher et. al, Atmospheric Environment, 44, 8-14, 2009.
* Observational studies in WP cafés * 1-Hour PM2.5 exposure Guideline-Alberta Hammal et al., 2013