Dermal thirdhand smoke exposure induced epidermal alterations in human keratinocyte cells through oxidative damage and MMP-1 expression.

Thirdhand smoke (THS) is the residual cigarette smoke that settles on indoor surface fabrics, dust and can accumulate in the environment. Therefore, it can be a risk factor for individuals who have frequent dermal contact with THS-contaminated surfaces. In the present study, it was aimed to elucidate the toxicity of dermal THS exposure in HaCaT human keratinocytes. The THS was extracted from terrycloth exposed to 3R4F research cigarette smoke in a closed chamber and the adverse outcomes induced by THS were determined through assessment of cytotoxicity tests (MTT and NRU), intracellular GSH level, total SOD activity, matrix metalloproteinase-1 (MMP-1) and IL-6 levels. The wound healing capacity of THS-exposed keratinocytes was evaluated via scratch assay. A potent antioxidant isothiocyanate compound, sulforaphane (SFN), was used as a negative control. THS was dose-dependently cytotoxic (12.5%-100%, v/v) to the HaCaT cells through mitochondrial cell dysfunction (p < 0.01), which was ameliorated by SFN (0.62 µM) pre-treatment. In parallel, THS exposure significantly decreased the intracellular GSH deposits and T-SOD activity in keratinocytes. Collagen degradation through elevated MMP-1 expression was observed in THS-exposed cells in parallel with the delay of wound healing and increased pro-inflammatory response in a dose-dependent manner (p < 0.05). The findings are expected to raise awareness about THS as an environmental pollutant for skin, particularly in the highest-ranked countries in cigarette consumption. To conclude, these results might contribute to the studies on the importance of dermal exposure to THS in the pathogenesis of epidermal alterations and the other skin diseases.

Sex Dependent Occlusive Cardiovascular Disease Effects of Short-Term Thirdhand Smoke Exposure.

INTRODUCTION: Thirdhand smoke (THS) is associated with many public health and disease concerns, such as respiratory illness, cancer, lipidemia, and cardiovascular disease (CVD). We have previously shown a moderate to long-term exposure to THS increased risk of thrombosis. However, whether short-term exposure to THS would produce any effects in causing disease remains to be discovered. Therefore, this study investigated the impact of one-month THS exposure on platelet function and cytokine response in sex-dependent. METHODS: Secondhand smoke or clean air (CA) exposed upholstery materials for 1 week were kept in cages housed with 5-6 mice, and the procedure was repeated for 4 weeks. These THS-exposed mice were evaluated for thrombogenesis and platelet function assays. In addition, the cytokines expressions were evaluated from pooled serum (n=5). RESULTS: Compared to the CA group, the THS exposure significantly shortened tail bleeding time and carotid artery thrombus formation. Moreover, the female mice appeared more sensitive to THS exposure than males. Furthermore, platelet aggregation, dense granule secretion, and P-selectin activation markers were significantly elevated due to THS exposure. In addition, the high throughput screening showed at least 30 cytokines differentially modulated by THS in females relative to 26 in male mice. CONCLUSION: Collectively, these results demonstrate that one month of THS exposure represents a high health risk, in part, by triggering a prothrombotic phenotype that appears to be more significant in females, who are at a much higher risk for occlusive CVD. Additionally, changes in cytokine levels mediate some of the THS-induced occlusive effects. IMPLICATIONS: This study revealed that THS exposure in one month is detrimental to the cardiovascular health of both sexes; however, females could be more aggressively affected than males. In addition, interleukins and chemokines could be critical factors for initiating prothrombotic activity due to THS exposure.

Distinguishing Exposure to Secondhand and Thirdhand Tobacco Smoke among U.S. Children Using Machine Learning: NHANES 2013-2016.

While the thirdhand smoke (THS) residue from tobacco smoke has been recognized as a distinct public health hazard, there are currently no gold standard biomarkers to differentiate THS from secondhand smoke (SHS) exposure. This study used machine learning algorithms to assess which combinations of biomarkers and reported tobacco smoke exposure measures best differentiate children into three groups: no/minimal tobacco smoke exposure (NEG); predominant THS exposure (TEG); and mixed SHS and THS exposure (MEG). Participants were 4485 nonsmoking 3-17-year-olds from the National Health and Nutrition Examination Survey 2013-2016. We fitted and tested random forest models, and the majority (76%) of children were classified in NEG, 16% were classified in TEG, and 8% were classified in MEG. The final classification model based on reported exposure, biomarker, and biomarker ratio variables had a prediction accuracy of 95%. This final model had prediction accuracies of 100% for NEG, 88% for TEG, followed by 71% for MEG. The most important predictors were the reported number of household smokers, serum cotinine, serum hydroxycotinine, and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In the absence of validated biomarkers specific to THS, comprehensive biomarker and questionnaire data for tobacco smoke exposure can distinguish children exposed to SHS and THS with high accuracy.

Exposure to secondhand and thirdhand smoke in private vehicles: Measurements in air and dust samples.

BACKGROUND: This study aimed to estimate airborne nicotine concentrations and nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in settled dust from private cars in Spain and the UK. METHODS: We measured vapor-phase nicotine concentrations in a convenience sample of 45 private cars from Spain (N = 30) and the UK (N = 15) in 2017-2018. We recruited non-smoking drivers (n = 20), smoking drivers who do not smoke inside the car (n = 15), and smoking drivers who smoke inside (n = 10). Nicotine, cotinine, and three TSNAs (NNK, NNN, NNA) were also measured in settled dust in a random subsample (n = 20). We computed medians and interquartile ranges (IQR) of secondhand smoke (SHS) and thirdhand smoke (THS) compounds according to the drivers' profile. RESULTS: 24-h samples yielded median airborne nicotine concentrations below the limit of quantification (LOQ) (IQR:

Association between involuntary smoking and risk of cervical cancer in Chinese female never smokers: A prospective cohort study.

Involuntary smoking was a major public health problem for women in China. Previous studies mainly focused on secondhand smoke (SHS), which referred to direct exposure to smoke from burning cigarettes. Little evidence existed about the relationship between thirdhand smoke (THS), the residual tobacco smoke remaining in the environment after tobacco had been smoked, and cervical cancer. The China Kadoorie Biobank (CKB) study recruited 0.3 million female participants from 10 areas across China during 2004-2008. After an 11.2-year median follow-up, we documented 1094 cervical cancer cases. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SHS and THS with cervical cancer incidence, respectively and jointly. Overall, 60.3% reported weekly SHS exposure, and 83.2% had been exposed to THS. Daily SHS exposure and THS exposure at the enrollment were associated with elevated risks of cervical cancer incidence, with adjusted HRs (95% CI) of 1.22 (1.06,1.42) and 1.24 (1.03,1.49), respectively. The longer the exposure duration, the higher the risks (P for trend = 0.006, 0.035, respectively). Compared with those who were neither exposed to SHS nor THS, those exposed to both SHS and THS had the highest risk, with adjusted HRs (95% CI) of 1.29 (1.05,1.58). Area of residence, breastfeeding duration and heating fuel types are potential effect modifiers. Among Chinese females, both SHS and THS were associated with higher risks of cervical cancer incidence, and a dose-response relationship was found between the exposure duration and cervical cancer risk. Our findings reinforce the need for proactive strategies for tobacco control, to protect women health.

Secondhand smoke exposure in school children in Malta assessed through urinary biomarkers.

School children may be exposed to secondhand smoke (SHS) either at home, in transit or in social gatherings permitting smoking in their presence. Questionnaires about SHS often underestimate prevalence and extent of exposure. A more accurate tool is the use of biomarkers such as cotinine (COT) and trans-3'-hydrocycotinine (3HC) as biomarkers of SHS exposure, alongside 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a reduction product in the body of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), both potent carcinogens. We measured urinary COT, 3HC and total NNAL using sensitive and specific high-performance LC-MS/MS methods. The limit of quantification (LOQ) for each assay were 0.05 ng/mL, 0.1 ng/mL and 0.25 pg/mL respectively. The aim of this study was to evaluate the exposure to SHS of school children (9-11 years), from five public schools in the island of Malta, from questionnaire information about smoking at home and verify it by urinary biomarker data of COT, 3HC and NNAL. These biomarkers were measurable in 99.4%, 95.4% and 98.3% of the participating children respectively. From the children reporting smoking at home, 11% had a history of asthma and had COT, 3HC and NNAL geometric mean concentrations double compared to the non-asthmatic group. In has been confirmed that non-smokers exposed to SHS and THS have a higher NNAL/COT ratio than the group identified as smokers according to specific and defined COT threshold levels (despite the fact that a priori, the entire study group was composed of non-smokers). The implication of high measured levels of urinary NNAL in children should be of concern given its potency. A main effects multifactor ANOVA model was developed and the children's house and school locations and the smoking frequency were statistically significant to predict the levels of the three metabolites. For 3HC only, the status of the employment of the mother was also an important predictor.

The effects of thirdhand smoke on reproductive health.

Tobacco smoke is an environmental pollutant that can cause follicle destruction and oocyte dysfunction. Thirdhand smoke (THS) is residual tobacco smoke existing in the environment long after cigarettes have been extinguished, which can react with other environmental compounds to produce secondary pollutants. THS contains a variety of toxic and harmful chemicals, such as nicotine and 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a logical biomarker of THS exposure. The health hazards of THS exposure and its components have been researched in recent years. In this review, we have summarized research progress on the effects of THS exposure on organs in mice and humans especially on the reproductive system. This review may help evaluate the health risks of THS, in particular reproduction and offspring health. We hope this review will guide public health education on the dangers of THS exposure and promotion of healthy living habits.

Exposure of Mice to Thirdhand Smoke Modulates In Vitro and In Vivo Platelet Responses.

Smoking is a risk factor for a variety of deleterious conditions, such as cancer, respiratory disease and cardiovascular disease. Thrombosis is an important and common aspect of several cardiovascular disease states, whose risk is known to be increased by both first- and secondhand smoke. More recently, the residual cigarette smoke that persists after someone has smoked (referred to as thirdhand smoke or THS) has been gaining more attention, since it has been shown that it also negatively affects health. Indeed, we have previously shown that 6-month exposure to THS increases the risk of thrombogenesis. However, neither the time-dependence of THS-induced thrombus formation, nor its sex dependence have been investigated. Thus, in the present study, we investigated these issues in the context of a shorter exposure to THS, specifically 3 months, in male and female mice. We show that the platelets from 3-month THS-exposed mice exhibited enhanced activation by agonists. Moreover, we also show that mice of both sexes exposed to THS have decreased tail bleeding as well as decreased thrombus occlusion time. In terms of the role of sex, intersex disparities in thrombus development and hemostasis as well as in platelet aggregation were, interestingly, observed. Together, our findings show that exposing mice to THS for 3 months is sufficient to predispose them to thrombosis; which seems to be driven, at least in part, by an increased activity in platelets, and that it does not manifest equally in both sexes.

Capability of Relative Odor Level Monitors to Measure the Odor of Thirdhand Smoke.

We investigated the probability of measuring the odor of thirdhand smoke using four odor-measuring monitors and three gas detector tubes. We measured the changes in tobacco odor on paper towels and cloth products over time. The results of the measurements were plotted against time to obtain an exponential approximation curve. The coefficient of x and the R2 values were calculated from this curve. The odor indicated by four types of odor-measuring monitors and three types of gas detector tubes decreased exponentially over time. The curves obtained from all measuring devices had coefficients of ex between -0.001 and -0.021, and R2 values of >0.8. The reproducibility of measuring relative odor levels through all measuring devices was high, suggesting a good capability of measuring thirdhand smoke odor. Two different odor-level standard gases can be used for the calibration of the regression curve for each monitor.

In utero and early-life exposure to thirdhand smoke causes profound changes to the immune system.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.

Differential associations of hand nicotine and urinary cotinine with children's exposure to tobacco smoke and clinical outcomes.

BACKGROUND: Children's overall tobacco smoke exposure (TSE) consists of both inhalation of secondhand smoke (SHS) and ingestion, dermal uptake, and inhalation of thirdhand smoke (THS) residue from dust and surfaces in their environments. OBJECTIVES: Our objective was to compare the different roles of urinary cotinine as a biomarker of recent overall TSE and hand nicotine as a marker of children's contact with nicotine pollution in their environments. We explored the differential associations of these markers with sociodemographics, parental smoking, child TSE, and clinical diagnoses. METHODS: Data were collected from 276 pediatric emergency department patients (Median age = 4.0 years) who lived with a cigarette smoker. Children's hand nicotine and urinary cotinine levels were determined using LC-MS/MS. Parents reported tobacco use and child TSE. Medical records were reviewed to assess discharge diagnoses. RESULTS: All children had detectable hand nicotine (GeoM = 89.7ng/wipe; 95 % CI = [78.9; 102.0]) and detectable urinary cotinine (GeoM = 10.4 ng/ml; 95%CI = [8.5; 12.6]). Although hand nicotine and urinary cotinine were highly correlated (r = 0.62, p < 0.001), urinary cotinine geometric means differed between racial groups and were higher for children with lower family income (p < 0.05), unlike hand nicotine. Independent of urinary cotinine, age, race, and ethnicity, children with higher hand nicotine levels were at increased risk to have discharge diagnoses of viral/other infectious illness (aOR = 7.49; 95%CI = [2.06; 27.24], p = 0.002), pulmonary illness (aOR = 6.56; 95%CI = [1.76; 24.43], p = 0.005), and bacterial infection (aOR = 5.45; 95%CI = [1.50; 19.85], p = 0.03). In contrast, urinary cotinine levels showed no associations with diagnosis independent of child hand nicotine levels and demographics. DISCUSSION: The distinct associations of hand nicotine and urinary cotinine suggest the two markers reflect different exposure profiles that contribute differentially to pediatric illness. Because THS in a child's environment directly contributes to hand nicotine, additional studies of children of smokers and nonsmokers are warranted to determine the role of hand nicotine as a marker of THS exposure and its potential role in the development of tobacco-related pediatric illnesses.

Thirdhand smoke associations with the gut microbiomes of infants admitted to a neonatal intensive care unit: An observational study.

INTRODUCTION: Microbiome differences have been found in adults who smoke cigarettes compared to non-smoking adults, but the impact of thirdhand smoke (THS; post-combustion tobacco residue) on hospitalized infants' rapidly developing gut microbiomes is unexplored. Our aim was to explore gut microbiome differences in infants admitted to a neonatal ICU (NICU) with varying THS-related exposure. METHODS: Forty-three mother-infant dyads (household member[s] smoke cigarettes, n = 32; no household smoking, n = 11) consented to a carbon monoxide-breath sample, bedside furniture nicotine wipes, infant-urine samples (for cotinine [nicotine's primary metabolite] assays), and stool collection (for 16S rRNA V4 gene sequencing). Negative binomial regression modeled relative abundances of 8 bacterial genera with THS exposure-related variables (i.e., household cigarette use, surface nicotine, and infant urine cotinine), controlling for gestational age, postnatal age, antibiotic use, and breastmilk feeding. Microbiome-diversity outcomes were modeled similarly. Bayesian posterior probabilities (PP) ≥75.0% were considered meaningful. RESULTS: A majority of infants (78%) were born pre-term. Infants from non-smoking homes and/or with lower NICU-furniture surface nicotine had greater microbiome alpha-diversity compared to infants from smoking households (PP ≥ 75.0%). Associations (with PP ≥ 75.0%) of selected bacterial genera with urine cotinine, surface nicotine, and/or household cigarette use were evidenced for 7 (of 8) modeled genera. For example, lower Bifidobacterium relative abundance associated with greater furniture nicotine (IRR<0.01 [<0.01, 64.02]; PP = 87.1%), urine cotinine (IRR = 0.08 [<0.01,2.84]; PP = 86.9%), and household smoking (IRR<0.01 [<0.01, 7.38]; PP = 96.0%; FDR p < 0.05). CONCLUSIONS: THS-related exposure was associated with microbiome differences in NICU-admitted infants. Additional research on effects of tobacco-related exposures on healthy infant gut-microbiome development is warranted.

Cotton pillows: A novel field method for assessment of thirdhand smoke pollution.

Thirdhand smoke (THS) is the residue left behind by secondhand smoke (SHS) that accumulates in indoor environments. THS chemicals can persist long after smoking has ceased and can re-emit semivolatile compounds back into the air. Measuring tobacco smoke pollution in real-world field setting can be technically complex, expensive, and intrusive. This study placed pillows in homes of former smokers and examined how much nicotine adsorbed to them over a three-week period. Organic cotton pillows were placed in the homes of 8 former smokers following the first week after verified smoking cessation until the fourth week. For comparison, pillows were also placed in 4 homes of nonsmokers. Nicotine concentrations were determined in the pillow case, fabric, and cotton filling, using isotope-dilution liquid chromatography tandem mass spectrometry. Cotton pillows placed in homes of former smokers absorbed on average 21.5 µg of nicotine. Nicotine concentration per gram of material significantly differed between pillow components (p < 0.001) and was highest for the pillow case (257 ng/g), followed by the pillow fabric (97 ng/g), and the pillow filling (17 ng/g). Nicotine levels in pillows placed in nonsmokers' homes did not differ from laboratory blanks (p > 0.40), or between pillow components (p > 0.40). In the absence of any smoking activity, cotton pillows absorbed significant amounts of nicotine emitted from THS reservoirs in the homes of former smokers. Given the much higher concentrations of SHS in the homes of active smokers, fabrics found throughout the home of a smoker are likely to store a substantial mass of tobacco smoke toxicants. Cotton pillows present a novel method that could be of interest to researchers requiring robust and unobtrusive methods to examine tobacco smoke pollution in real-world field settings.

Contribution of thirdhand smoke to overall tobacco smoke exposure in pediatric patients: study protocol.

BACKGROUND: Thirdhand smoke (THS) is the persistent residue resulting from secondhand smoke (SHS) that accumulates in dust, objects, and on surfaces in homes where tobacco has been used, and is reemitted into air. Very little is known about the extent to which THS contributes to children's overall tobacco smoke exposure (OTS) levels, defined as their combined THS and SHS exposure. Even less is known about the effect of OTS and THS on children's health. This project will examine how different home smoking behaviors contribute to THS and OTS and if levels of THS are associated with respiratory illnesses in nonsmoking children. METHODS: This project leverages the experimental design from an ongoing pediatric emergency department-based tobacco cessation trial of caregivers who smoke and their children (NIHR01HD083354). At baseline and follow-up, we will collect urine and handwipe samples from children and samples of dust and air from the homes of smokers who smoke indoors, have smoking bans or who have quit smoking. These samples will be analyzed to examine to what extent THS pollution at home contributes to OTS exposure over and above SHS and to what extent THS continues to persist and contribute to OTS in homes of smokers who have quit or have smoking bans. Targeted and nontargeted chemical analyses of home dust samples will explore which types of THS pollutants are present in homes. Electronic medical record review will examine if THS and OTS levels are associated with child respiratory illness. Additionally, a repository of child and environmental samples will be created. DISCUSSION: The results of this study will be crucial to help close gaps in our understanding of the types, quantity, and clinical effects of OTS, THS exposure, and THS pollutants in a unique sample of tobacco smoke-exposed ill children and their homes. The potential impact of these findings is substantial, as currently the level of risk in OTS attributable to THS is unknown. This research has the potential to change how we protect children from OTS, by recognizing that SHS and THS exposure needs to be addressed separately and jointly as sources of pollution and exposure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02531594 . Date of registration: August 24, 2015.

Thirdhand smoke component can exacerbate a mouse asthma model through mast cells.

BACKGROUND: Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for asthma or asthma exacerbation if the disease is already present, how exposure to THS can influence the development or exacerbation of asthma remains unknown. OBJECTIVE: We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a mouse model elicited by means of repeated intranasal challenge with cockroach antigen (CRA). METHODS: Wild-type mice, α7 nicotinic acetylcholine receptor (nAChR)- or mast cell (MC)-deficient mice, and mice with MCs that lacked α7 nAChRs or were the host's sole source of α7 nAChRs were subjected to epicutaneous NNK exposure, intranasal CRA challenge, or both, and the severity of features of asthma pathology, including airway hyperreactivity, airway inflammation, and airway remodeling, was assessed. RESULTS: We found that α7 nAChRs were required to observe adverse effects of epicutaneous NNK exposure on multiple features of CRA-induced asthma pathology. Moreover, MC expression of α7 nAChRs contributed significantly to the ability of epicutaneous NNK exposure to exacerbate airway hyperreactivity to methacholine, airway inflammation, and airway remodeling in this model. CONCLUSION: Our results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a CRA-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.

Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice.

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk.

Update on thirdhand smoke: A comprehensive systematic review.

OBJECTIVE: The objective of this study is to perform a comprehensive review of the literature about thirdhand smoke (THS). METHODS: Systematic review of all aspects of THS. Standard methodological procedures were used to search the following databases through April 2018: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science (WOS) in Indo-European languages. To identify published grey literature, the first 200 hits from Google Scholar™ were evaluated. Clinical trial databases, conference proceedings, and reference lists from the identified articles were also searched. Two unblinded review authors independently assessed trials for inclusion in the review. These same reviewers also extracted study data in accordance with PRISMA guidelines. The study protocol was registered with PROSPERO (CRD42018083619). RESULTS: Sixty-eight articles were included in this systematic review. Of these, 28 analyzed the concentration of nicotine as a component of THS (the most commonly-used method to measure THS in those studies was chromatography, followed by the mass spectrometry), 21 evaluated the exposure and impact of THS on health (11 studies analyzed the effect of THS in cells [human and animal], 4 in animals, 1 in adults, and 5 in children), 16 investigated the beliefs, behaviours, and policies related to THS, and 3 evaluated other aspects such as THS in e-cigarettes or hookahs. In these 68 studies, THS was determined by measuring the following components: nicotine (30 studies), nitrosamines (17 studies) and cotinine (15 studies). The findings from most of these studies suggest a potential health impact of THS exposure (i.e.: cytotoxicity, metabolic alterations in metabolism, in glycemia; or cell structure; alterations in liver, lung, skin and behaviour in mice), and low awareness about the risks of THS among the general population. CONCLUSIONS: Numerous specific biomarkers of THS were evaluated, with the most common being nicotine, nitrosamines, and cotinine. The most common method of preparing THS dust samples were cotton wipes, while chromatography, used alone or coupled with mass spectrometry, was the most common analytical technique. We have tried to establish common bases after reviewing all the current literature of the THS although, there is great heterogeneity between the studies and we have not always succeeded. The studies in this review demonstrate the harmful effects of THS on health in cells, in animal models, and in people including children. However, in people, the long-term effects remain unknown and more research is needed. These studies show that knowledge about THS and its potential harmful effects are poorly understood among the general population. For this reason, THS should receive greater emphasis in education and awareness policies.

Adverse Health Effects of Thirdhand Smoke: From Cell to Animal Models.

The newly identified smoke hazard, thirdhand smoke (THS), has gained public attention in recent years but its health impact and biological effects are largely unknown. THS may be defined by "the four Rs": tobacco chemicals that remain, react, re-emit, and/or are resuspended long after active smoking has ceased. This review summarizes recent research progress in the effects of THS on genotoxicity, metabolism and early life development using cellular and animal models. We first reported that THS generated in laboratory systems caused significant DNA damage in human cell lines. Our finding that THS significantly induces oxidative base lesions has been confirmed in skin wounds of mice models exposed to THS. THS also induced metabolomic changes in human reproductive cell lines. Furthermore, we demonstrated that early exposure to THS not only negatively impacts body weight in both male and female mice, but also induces persistent changes to immunological parameters in peripheral blood in these mice. These results indicate that THS is genotoxic at realistic experimental doses and that there may be a window of susceptibility for some forms of cellular damage induced by THS.

Guidance for the Clinical Management of Thirdhand Smoke Exposure in the Child Health Care Setting.

OBJECTIVE: To explain the concept of thirdhand smoke and how it can be used to protect the health of children and improve delivery of tobacco control interventions for parents in the child health care setting. METHODS: Review of the literature and descriptive report. RESULTS: The thirdhand smoke concept has been used in the CEASE intervention to improve the delivery of tobacco control counseling and services to parents. Materials and techniques have been developed for the child health care setting that use the concept of thirdhand smoke. Scientific findings demonstrate that thirdhand smoke exposure is harmful and establishes the need for clinicians to communicate the cessation imperative: the only way to protect non-smoking household members from thirdhand smoke is for all household smokers to quit smoking completely. As the scientific knowledge of thirdhand smoke increases, advocates will likely rely on it to encourage completely smoke-free places. CONCLUSION: Recent scientific studies on thirdhand smoke are impelling further research on the topic, spurring the creation of tobacco control policies to protect people from thirdhand smoke and stimulating improvements to the delivery of tobacco control counseling and services to parents in child health care settings.

Reactions to Thirdhand Smoke are Associated with Openness to Smoking in Young Never Smoking Children.

To investigate the associations between reactions to thirdhand smoke (THS) and openness to smoking in young children. In a school-based survey in Hong Kong, 4762 Chinese primary school students reported their reactions to THS (one or more of 'pleasant/happy', 'nausea', 'excited', 'heart beat faster', 'relaxed', 'dislike the smell', 'like the smell', 'dizzy', 'coughing/choking', 'eye uncomfortable' and 'none of the above'), smoking status and openness to smoking (lack of a firm intention not to smoke). Factor structure of reactions to THS was investigated with factor scores calculated and categorised. Logistic regression yielded adjusted odds ratio (AOR) of openness to smoking for reactions to THS. Factor analysis yielded two factors including 5 and 4 reactions, which were generally deemed negative and positive, respectively. The proportions of students with factor scores ≥1 for negative and positive reactions were 51.3 and 6.3 %, respectively. In never smokers, openness to smoking was negatively associated with 'dislike the smell' (AOR 0.52, 95 % CI 0.39-0.68), 'coughing/choking' (0.53, 0.38-0.75), 'eye uncomfortable' (0.62, 0.40-0.95) and negative reaction factor score of 2-5 (vs. 0) (0.59, 0.40-0.88), and was positively associated with 'pleasant/happy' (2.80, 1.54-5.09), 'excited' (2.83, 1.17-6.87), 'like the smell' (3.06, 1.49-6.26) and positive reaction factor score of 1-4 (vs. 0) (2.86, 1.83-4.48). In experimental or former smokers, fewer associations reached statistical significance. Negative and positive reactions to THS were negatively and positively associated with openness to smoking, respectively, in young never smoking children.