Suzaynn F. Schick

Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production.

OBJECTIVES This study sought to analyze the effects of acute secondhand smoke (SHS) exposure on the number and function of endothelial progenitor cells (EPCs) over 24 h. BACKGROUND Secondhand smoke increases the risk of vascular disease and is a major public health concern, but the mechanism(s) of action are not fully understood. METHODS Healthy nonsmokers (age SEM 30.3 +/- 1.3 years, n = 10) were exposed to 30 min of SHS yielding cotinine levels commonly observed in passive smokers and to smokefree air on 2 separate days. Measurements were taken before exposure (baseline), immediately after (0 h), and at 1 h, 2.5 h, and 24 h after. The EPCs (CD133(+)/KDR(+), CD34(+)/KDR(+)) and endothelial microparticles (EMPs: CD31(+)/CD41(-), CD144(+), CD62e(+)) were determined in blood using flow cytometry. The EPC chemotaxis toward vascular endothelial growth factor was measured. Endothelial function was assessed as flow-mediated dilation (FMD) using ultrasound. RESULTS Secondhand smoke exposure increased EPCs and plasma vascular endothelial growth factor and completely abolished EPC chemotaxis during 24 h after exposure. Secondhand smoke increased EMPs and decreased FMD. Although FMD returned to baseline at 2.5 h, EMPs and vascular endothelial growth factor levels remained elevated at 24 h, suggesting endothelial activation and injury with functional impairment of the vascular endothelium. Exposure to smokefree air had no effect. Incubation of EPCs from nonexposed subjects with plasma isolated from SHS-exposed subjects in vitro decreased chemotaxis by blockade of vascular endothelial growth factor-stimulated nitric oxide production. CONCLUSIONS Brief exposure to real-world levels of SHS leads to sustained vascular injury characterized by mobilization of dysfunctional EPCs with blocked nitric oxide production. Our results suggest that SHS not only affects the vascular endothelium, but also the function of EPCs.

Thirdhand Tobacco Smoke: Emerging Evidence and Arguments for a Multidisciplinary Research Agenda

Background: There is broad consensus regarding the health impact of tobacco use and secondhand smoke exposure, yet considerable ambiguity exists about the nature and consequences of thirdhand smoke (THS). Objectives: We introduce definitions of THS and THS exposure and review recent findings about constituents, indoor sorption–desorption dynamics, and transformations of THS; distribution and persistence of THS in residential settings; implications for pathways of exposure; potential clinical significance and health effects; and behavioral and policy issues that affect and are affected by THS. Discussion: Physical and chemical transformations of tobacco smoke pollutants take place over time scales ranging from seconds to months and include the creation of secondary pollutants that in some cases are more toxic (e.g., tobacco-specific nitrosamines). THS persists in real-world residential settings in the air, dust, and surfaces and is associated with elevated levels of nicotine on hands and cotinine in urine of nonsmokers residing in homes previously occupied by smokers. Much still needs to be learned about the chemistry, exposure, toxicology, health risks, and policy implications of THS. Conclusion: The existing evidence on THS provides strong support for pursuing a programmatic research agenda to close gaps in our current understanding of the chemistry, exposure, toxicology, and health effects of THS, as well as its behavioral, economic, and sociocultural considerations and consequences. Such a research agenda is necessary to illuminate the role of THS in existing and future tobacco control efforts to decrease smoking initiation and smoking levels, to increase cessation attempts and sustained cessation, and to reduce the cumulative effects of tobacco use on morbidity and mortality.

Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke

Background: Exposure to secondhand smoke causes lung cancer; however, there are little data in the open literature on the in vivo toxicology of fresh sidestream cigarette smoke to guide the debate about smoke-free workplaces and public places. Objective: To investigate the unpublished in vivo research on sidestream cigarette smoke done by Philip Morris Tobacco Company during the 1980s at its Institut für Biologische Forschung (INBIFO). Methods: Analysis of internal tobacco industry documents now available at the University of California San Francisco Legacy Tobacco Documents Library and other websites. Results: Inhaled fresh sidestream cigarette smoke is approximately four times more toxic per gram total particulate matter (TPM) than mainstream cigarette smoke. Sidestream condensate is approximately three times more toxic per gram and two to six times more tumourigenic per gram than mainstream condensate by dermal application. The gas/vapour phase of sidestream smoke is responsible for most of the sensory irritation and respiratory tract epithelium damage. Fresh sidestream smoke inhibits normal weight gain in developing animals. In a 21day exposure, fresh sidestream smoke can cause damage to the respiratory epithelium at concentrations of 2 μg/l TPM. Damage to the respiratory epithelium increases with longer exposures. The toxicity of whole sidestream smoke is higher than the sum of the toxicities of its major constituents. Conclusion: Fresh sidestream smoke at concentrations commonly encountered indoors is well above a 2 μg/m3 reference concentration (the level at which acute effects are unlikely to occur), calculated from the results of the INBIFO studies, that defines acute toxicity to humans. Smoke-free public places and workplaces are the only practical way to protect the public health from the toxins in sidestream smoke.

Thirdhand smoke causes DNA damage in human cells

Exposure to thirdhand smoke (THS) is a newly described health risk. Evidence supports its widespread presence in indoor environments. However, its genotoxic potential, a critical aspect in risk assessment, is virtually untested. An important characteristic of THS is its ability to undergo chemical transformations during aging periods, as demonstrated in a recent study showing that sorbed nicotine reacts with the indoor pollutant nitrous acid (HONO) to form tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The goal of this study was to assess the genotoxicity of THS in human cell lines using two in vitro assays. THS was generated in laboratory systems that simulated short (acute)- and long (chronic)-term exposures. Analysis by liquid chromatography-tandem mass spectrometry quantified TSNAs and common tobacco alkaloids in extracts of THS that had sorbed onto cellulose substrates. Exposure of human HepG2 cells to either acute or chronic THS for 24h resulted in significant increases in DNA strand breaks in the alkaline Comet assay. Cell cultures exposed to NNA alone showed significantly higher levels of DNA damage in the same assay. NNA is absent in freshly emitted secondhand smoke, but it is the main TSNA formed in THS when nicotine reacts with HONO long after smoking takes place. The long amplicon-quantitative PCR assay quantified significantly higher levels of oxidative DNA damage in hypoxanthine phosphoribosyltransferase 1 (HPRT) and polymerase β (POLB) genes of cultured human cells exposed to chronic THS for 24h compared with untreated cells, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity. The findings of this study demonstrate for the first time that exposure to THS is genotoxic in human cell lines.

Sidestream cigarette smoke toxicity increases with aging and exposure duration

Objectives: To determine the effects of aging on the toxicity of sidestream tobacco smoke, the complex chemical mixture that enters the air from the lit end of burning cigarettes and constitutes the vast bulk of secondhand smoke. Design: Statistical analysis of data from controlled experimental exposures of Sprague Dawley rats to fresh and aged (for more than 30 minutes) sidestream smoke for up to 90 days followed by histological sectioning of the respiratory epithelium. The data were obtained from a series of experiments conducted at Philip Morris’ formerly secret INBIFO (Institut für Biologische Forschung) laboratory in Germany. Results: Using total particulate material as the measure of smoke exposure, aging sidestream cigarette smoke for at least 30 minutes increases its toxicity fourfold for 21 day exposures and doubles the toxicity for 90 day exposures, relative to fresh sidestream smoke. Conclusions: These results help explain the relatively large biological effects of secondhand smoke compared to equivalent mass doses of mainstream smoke.

Concentrations of the Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Sidestream Cigarette Smoke Increase after Release into Indoor Air: Results from Unpublished Tobacco Industry Research

Research has shown that the toxicity of sidestream cigarette smoke, the primary constituent of secondhand smoke, increases over time. To find potential mechanisms that would explain the increase in sidestream smoke toxicity over time, we analyzed unpublished research reports from Philip Morris Co. using the internal tobacco industry documents now available at the University of California San Francisco Legacy Tobacco Documents Library and other Web sites. Unpublished research from Philip Morris Tobacco Company shows that 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone (NNK), a highly carcinogenic tobacco-specific nitrosamine, can form in sidestream cigarette smoke after it has been released into ambient air. In experiments done between 1983 and 1997, Philip Morris scientists measured the concentration of NNK in sidestream smoke in a sealed stainless steel test chamber at initial particle concentrations of 24 mg/m3 over the course of 6 to 18 h. They repeatedly showed that airborne NNK concentrations in sidestream cigarette smoke can increase by 50% to 200% per hour during the first 6 h after cigarettes are extinguished. Two experiments done in a real office showed that NNK concentrations increase for the first 2 h after cigarettes are extinguished. If NNK formation also occurs in the lower smoke concentrations observed in real smoking environments, these results suggest that nitrosation of nicotine and/or nicotine breakdown products in aging secondhand smoke is a significant contributor to nitrosamine exposure in humans. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1547–53)

Thirdhand cigarette smoke in an experimental chamber: evidence of surface deposition of nicotine, nitrosamines and polycyclic aromatic hydrocarbons and de novo formation of NNK

Background A growing body of evidence shows that secondhand cigarette smoke undergoes numerous chemical changes after it is released into the air: it can adsorb to indoor surfaces, desorb back into the air and undergo chemical changes as it ages. Objectives To test the effects of aging on the concentration of polycyclic aromatic hydrocarbons (PAHs), nicotine and tobacco-specific nitrosamines in cigarette smoke. Methods We generated sidestream and mainstream cigarette smoke with a smoking machine, diluted it with conditioned filtered air, and passed it through a 6 m3 flow reactor with air exchange rates that matched normal residential air exchange rates. We tested the effects of 60 min aging on the concentration of 16 PAHs, nicotine, cotinine and tobacco-specific nitrosamines. We also measured sorption and deposition of nicotine, cotinine and tobacco-specific nitrosamines on materials placed within the flow reactor. Results We observed mass losses of 62% for PAHs, 72%, for nicotine, 79% for N-nitrosonornicotine and 80% for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Extraction of cotton cloth exposed to smoke yielded nicotine and NNK. The ratio of NNK:nicotine on the exposed cloth was 10-fold higher than that in aerosol samples. Conclusions Our data suggest that the majority of the PAHs, nicotine, cotinine and tobacco-specific nitrosamines that are released during smoking in homes and public places deposit on room surfaces. These data give an estimate of the potential for accumulation of carcinogens in thirdhand cigarette smoke. Exposure to PAHs and tobacco-specific nitrosamines, through dermal absorption and inhalation of contaminated dust, may contribute to smoking-attributable morbidity and mortality.

Thirdhand Cigarette Smoke: Factors Affecting Exposure and Remediation

Thirdhand smoke (THS) refers to components of secondhand smoke that stick to indoor surfaces and persist in the environment. Little is known about exposure levels and possible remediation measures to reduce potential exposure in contaminated areas. This study deals with the effect of aging on THS components and evaluates possible exposure levels and remediation measures. We investigated the concentration of nicotine, five nicotine related alkaloids, and three tobacco specific nitrosamines (TSNAs) in smoke exposed fabrics. Two different extraction methods were used. Cotton terry cloth and polyester fleece were exposed to smoke in controlled laboratory conditions and aged before extraction. Liquid chromatography-tandem mass spectrometry was used for chemical analysis. Fabrics aged for 19 months after smoke exposure retained significant amounts of THS chemicals. During aqueous extraction, cotton cloth released about 41 times as much nicotine and about 78 times the amount of tobacco specific nitrosamines (TSNAs) as polyester after one hour of aqueous extraction. Concentrations of nicotine and TSNAs in extracts of terry cloth exposed to smoke were used to estimate infant/toddler oral exposure and adult dermal exposure to THS. Nicotine exposure from THS residue can be 6.8 times higher in toddlers and 24 times higher in adults and TSNA exposure can be 16 times higher in toddlers and 56 times higher in adults than what would be inhaled by a passive smoker. In addition to providing exposure estimates, our data could be useful in developing remediation strategies and in framing public health policies for indoor environments with THS.

Old ways, new means: tobacco industry funding of academic and private sector scientists since the Master Settlement Agreement

When, as a condition of the Master Settlement Agreement (MSA) in 1998, US tobacco companies disbanded the Council for Tobacco Research and the Center for Indoor Air Research, they lost a vital connection to scientists in academia and the private sector. The aim of this paper was to investigate two new research projects funded by US tobacco companies by analysis of internal tobacco industry documents now available at the University of California San Francisco (San Francisco, California, USA) Legacy tobacco documents library, other websites and the open scientific literature. Since the MSA, individual US tobacco companies have replaced their industry-wide collaborative granting organisations with new, individual research programmes. Philip Morris has funded a directed research project through the non-profit Life Sciences Research Office, and British American Tobacco and its US subsidiary Brown and Williamson have funded the non-profit Institute for Science and Health. Both of these organisations have downplayed or concealed their true level of involvement with the tobacco industry. Both organisations have key members with significant and long-standing financial relationships with the tobacco industry. Regulatory officials and policy makers need to be aware that the studies these groups publish may not be as independent as they seem.

One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function

Background Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke‐free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction. Methods and Results We measured endothelial function as femoral artery flow‐mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real‐world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid‐independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium‐independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air. Conclusions One minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana.