"Inhaling hazards, exhaling insights: a systematic review unveiling the silent health impacts of secondhand smoke pollution on children and adolescents.

The health risks of smoking are widely known, but the impact of secondhand smoke on children and adolescents is often underestimated. Despite efforts to reduce smoking, exposure to secondhand smoke remains a significant public health concern, especially for young individuals. This systematic review aims to explore the health impacts of secondhand smoking on children and adolescents. Following PRISMA guidelines, 18 eligible studies from 8 countries published between 2015 and 2023 were identified through PubMed, SCOPUS, and Web of Science databases. Findings revealed that passive smoking is associated with respiratory issues like asthma and respiratory infections in children and adolescents aged 4 months to 18 years. Significant correlations were found between asthma severity and cotinine levels, a marker of passive smoking. Additionally, metabolic issues, cardiovascular effects, and ophthalmological changes, and alterations in neurocognitive functions, were noted. Urgent public health interventions are needed to reduce smoking prevalence and protect this vulnerable demographic.

Tobacco smoke condensate-induced senescence in endothelial cells was ameliorated by colchicine treatment via suppression of NF-κB and MAPKs P38 and ERK pathways activation.

Smoking is the major cause of cardiovascular diseases and cancer. It induces oxidative stress, leading to DNA damage and cellular senescence. Senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase, which are known to play a vital role in the initiation and progression of cardiovascular diseases and metastasis in cancer. The current study investigated the smoking induced cellular senescence and employed colchicine that blocked senescence in endothelial cells exposed to tobacco smoke condensate. Colchicine prevented oxidative stress and DNA damage in tobacco smoke-condensate-treated endothelial cells. Colchicin reduced ß-gal activity, improved Lamin B1, and attenuated cell growth arrest markers P21 and P53. Colchicine also ameliorated the expression of SASP factors and inhibited the activation of NF-kB and MAPKs P38 and ERK. In summary, colchicine inhibited tobacco smoke condensate-induced senescence in endothelial cells by blocking the activation of NF-kB and MAPKs P38 and ERK.

Early life exposure to secondhand tobacco smoke and eating behaviors at age 12 years.

BACKGROUND: Prenatal or early childhood secondhand tobacco smoke (SHS) exposure increases obesity risk. However, the potential mechanisms underlying this association are unclear, but obesogenic eating behaviors are one pathway that components of SHS could perturb. Our aim was to assess associations of prenatal and early childhood SHS exposure with adolescent eating behaviors. METHODS: Data came from a prospective pregnancy and birth cohort (N = 207, Cincinnati, OH). With multiple informant models, we estimated associations of prenatal (mean of 16 and 26 weeks of gestation maternal serum cotinine concentrations) and early childhood cotinine (average concentration across ages 12, 24, 36, and 48 months) with eating behaviors at age 12 years (Child Eating Behaviors Questionnaire). We tested whether associations differed by exposure periods and adolescent's sex. Models adjusted for maternal and child covariates. RESULTS: We found no statistically significant associations between cotinine measures and adolescent's eating behaviors. Yet, in females, prenatal cotinine was associated with greater food responsiveness (ß: 0.23; 95% CI: 0.08, 0.38) and lower satiety responsiveness (ß: -0.14; 95% CI: -0.26, -0.02); in males, prenatal and postnatal cotinine was related to lower food responsiveness (prenatal: ß: -0.25; 95% CI: -0.04, -0.06; postnatal: ß: -0.36; 95% CI: -0.06, -0.11). No significant effect modification by sex or exposure window was found for other eating behaviors. CONCLUSION: Prenatal and early childhood SHS exposures were not related to adolescent's eating behavior in this cohort; however, biological sex may modify these associations.

Role of reactive carbonyls and superoxide radicals in protein damage by cigarette smoke extracts: Comparison of Heat-not-Burn e-cigarettes to conventional cigarettes.

Oxidative protein damage involving carbonylation of respiratory tract proteins typically accompanies exposure to tobacco smoke. Such damage can arise via multiple mechanisms, including direct amino acid oxidation by reactive oxygen species or protein adduction by electrophilic aldehydes. This study investigated the relative importance of these pathways during exposure of a model protein to fresh cigarette emission extracts. Briefly, protein carbonyl adducts were estimated in bovine serum albumin following incubation in buffered solutions with whole cigarette emissions extracts prepared from either a single 1R6F research cigarette or a single "Heat-not-Burn" e-cigarette. Although both extracts caused concentration-dependent protein carbonylation, conventional cigarette extracts produced higher adduct yields than e-cigarette extracts. Superoxide radical generation by conventional and e-cigarette emissions was assessed by monitoring nitro blue tetrazolium reduction and was considerably lower in extracts made from "Heat-Not-Burn" e-cigarettes. The superoxide dismutase/catalase mimic EUK-134 strongly suppressed radical production by whole smoke extracts from conventional cigarettes, however, it did not diminish protein carbonyl adduction when incubating smoke extracts with the model protein. In contrast, edaravone, a neuroprotective drug with strong carbonyl-trapping properties, strongly suppressed protein damage without inhibiting superoxide formation. Although these findings require extension to appropriate cell-based and in vivo systems, they suggest reactive aldehydes in tobacco smoke make greater contributions to oxidative protein damage than smoke phase radicals.

Role of parental smoking and environmental tobacco smoke exposure in childhood cancer: A study using hair cotinine analysis and questionnaires.

OBJECTIVES: In the etiology of childhood cancers, many genetic and environmental factors play a role. One of these factors could be cigarette smoking, and the main source of tobacco smoke exposure of children is parental smoking. However, establishing a causal relationship between parental smoking and childhood cancers has proven challenging due to difficulties in accurately detecting tobacco smoke exposure METHODS: To address this issue, we used hair cotinine analysis and a questionnaire to get information about tobacco smoke exposures of pediatric cancer patients and healthy children. A total of 104 pediatric cancer patients and 99 healthy children participated in our study. Parental smoking behaviors (pre-conceptional, during pregnancy, and current smoking) and environmental tobacco smoke (ETS) exposures of children are compared. RESULTS: We have found no differences between two groups by means of maternal smoking behaviors. However, the rates of paternal pre-conceptional smoking and smoking during pregnancy were significantly low in cancer patients (p < .05). These data suggest that social desirability bias among fathers of cancer patients may have contributed to this discrepancy. According to questionnaire, cancer patients had significantly lower ETS exposures than healthy children (p < .05). However, ETS exposure assessment through cotinine analysis demonstrated that cancer patients had higher exposure to ETS compared to healthy children (p < .001). CONCLUSION: Our findings provide evidence supporting the potential role of smoking as a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.

Unraveling the link: environmental tobacco smoke exposure and its impact on infertility among American women (18-50 years).

Purpose: The detrimental effects of environmental tobacco smoke (ETS) on women's reproductive health have been widely recognized. However, the detailed association between exposure to environmental tobacco smoke and the incidence of infertility remains under-explored. This investigation focuses on exploring this potential connection. Methods: For this analysis, we extracted data from the US National Health and Nutrition Examination Survey (NHANES) database, covering the years 2013 to 2018, focusing on individuals with recorded serum cotinine levels and infertility information. ETS exposure and fertility status were analyzed as independent and dependent variables, respectively. We applied weighted multivariate logistic regression method to evaluate the impact of ETS on infertility, including subgroup analyses for more detailed insights. Results: The study encompassed 3,343 participants. Logistic regression analysis revealed a notable positive correlation between ETS exposure and infertility, with an odds ratio (OR) of 1.64 (95% Confidence Interval [CI]: 1.14-2.36). We observed a non-linear relationship between ETS exposure and infertility risk. Notably, infertility risk increased by 64% in serum cotinine levels above 0.136 compared to that in serum cotinine levels below 0.011. Further, subgroup analysis and interaction tests showed consistent results across different segments, underscoring the robustness of the ETS-infertility link. Conclusion: Our findings suggest that environmental tobacco smoke exposure may be a contributing factor to infertility. These results reinforce the recommendation for women in their reproductive years to avoid ETS exposure, especially when planning for pregnancy.

Environmental tobacco smoke exposure exaggerates bleomycin-induced collagen overexpression during pulmonary fibrogenesis.

Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism that ETS exposure augments pulmonary fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation. C57BL/6J and p16-3MR mice were exposed to ETS followed by bleomycin administration. ETS exposure exacerbated bleomycin-induced collagen and lysyl oxidase overexpression in the fibrotic lesion. ETS exposure also led to augmented bleomycin-induced upregulation of C3 and C3AR, which are pro-fibrotic markers. Moreover, overexpressed collagens and C3 levels were highly significant in males than females. The old mice (17 months old) were exposed to ETS and treated with bleomycin to induce fibrogenesis which is considered as an aging-associated disease. Fewer gene and protein dysregulations trends were identified between ETS exposure with the bleomycin group and the bleomycin alone group in old mice. Based on our findings, we suggested that ETS exposure increases the risk of developing severe lung fibrotic responses via collagen overexpression and lysyl oxidase-mediated collagen stabilization in the fibrotic lesion, and potentially affected the complement system activation induced by bleomycin. Further, male mice were more susceptible than females during fibrogenesis exacerbation. Thus ETS and bleomycin induced lung fibrotic changes via collagen-lysyl oxidase in an age-dependent mechanism.

The impact of secondhand smoke on failure of Helicobacter pylori therapy is not inferior to that of smoking.

BACKGROUND: Previous studies have shown the associations between smoking and failure to eradicate Helicobacter pylori (H. pylori), but less is known about the impact of secondhand tobacco smoke (SHS) on H. pylori eradication. METHODS: Between July 2022 to July 2023, 646 patients who received proton pump inhibitor (PPIs) as first-line H. pylori eradication therapy were recruited for the study. Information was obtained via the hospital database and a telephone questionnaire. Univariate and multivariate regression analysis were used to examine risk factors of H. pylori eradication failure. RESULTS: This was a single-center retrospective study consisting of 646 patients who received PPIs as first-line H. pylori eradication therapy. This included 122 smokers, 165 never-smokers with SHS, and 359 never-smokers with no SHS exposure. Compared with subjects in the "eradication success" group, those in the "eradication failure" group tended to have higher prevalence of smoke consumption and have higher prevalence of SHS exposure. In binary logistic regression analysis, smoking (OR 3.409, 95% CI: 1.782- 6.522, P<0.001) and SHS (OR 3.188, 95% CI: 1.726-5.886, P<0.001) were independent predictors of eradication failure. In addition, never-smokers with SHS exposure and smoking had similar effects on H. pylori eradication (OR, 0.893; 95% CI, 0.464 to 1.717, P value = 0.734). CONCLUSION: Both smoking and SHS are independent risk factors for H. pylori eradication failure. Furthermore, the impact of SHS is not inferior to smoking.

Airway inflammation in a novel mouse model of asthma-COPD overlap induced by co-exposure to papain and tobacco smoke.

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases associated with airway inflammation, which is the main pathogenesis. Although their causes and characteristics differ, in some cases, asthma and COPD may coexist in the same patient in a condition called asthma-COPD overlap (ACO). The prognosis of ACO is more unfavourable than those of asthma or COPD alone, without any treatment strategies demonstrating efficacy. Owing to its intricate spectrum of features, the detailed pathogenesis of how ACO exacerbates respiratory features remains unclear. In this study, we exposed papain-induced asthma model mice to tobacco smoke to establish an ACO mouse model, in which features of airway inflammation observed in both asthma and COPD were incorporated. This model exhibited distinctive mixed and corticosteroid-resistant airway inflammation and emphysematous changes that are characteristic of ACO. The novel mouse model established here is expected to significantly contribute to elucidating the mechanisms of the broad pathologies of ACO and identifying potential therapeutic targets.

Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.

Cancer remains a significant global health concern, with lung cancer consistently leading as one of the most common malignancies. Genetic aberrations involving receptor tyrosine kinases (RTKs) are known to be associated with cancer initiation and development, but RTK involvement in smoking-associated lung cancer cases is not well understood. The Insulin-like Growth Factor 1 Receptor (IGF-1R) is a receptor that plays a critical role in lung cancer development. Its signaling pathway affects the growth and survival of cancer cells, and high expression is linked to poor prognosis and resistance to treatment. Several reports have shown that by activating IGF-1R, tobacco smoke-related carcinogens promote lung cancer and chemotherapy resistance. However, the relationship between IGF-1R and cancer is complex and can vary depending on the type of cancer. Ongoing investigations are focused on developing therapeutic strategies to target IGF-1R and overcome chemotherapy resistance. Overall, this review explores the intricate connections between tobacco smoke-specific carcinogens and the IGF-1R pathway in lung carcinogenesis. This review further highlights the challenges in using IGF-1R inhibitors as targeted therapy for lung cancer due to structural similarities with insulin receptors. Overcoming these obstacles may require a comprehensive approach combining IGF-1R inhibition with other selective agents for successful cancer treatment.

Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers.

CONTEXT: Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. OBJECTIVE: This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. METHODS: Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, ß-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. RESULTS: Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. ß-Carotene was negatively correlated with the adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). CONCLUSION: These results are promising, and the study is now being conducted on a larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition.

INTRODUCTION: The growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear. OBJECTIVES: This study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied. METHODS: Data on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis. RESULTS: Individuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: -0.51, -0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements. CONCLUSIONS: Our findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.

Association of Zinc Intake, Tobacco Smoke Exposure, With Metabolic Syndrome: Evidence from NHANES 2007-2018.

The objective was to explore the effect modification of zinc (Zn) intake levels on the relationship of tobacco smoke exposure and risk of metabolic syndrome (MetS) in children and adolescents. We used data from 2007-2018 National Health and Nutrition Examination Survey (N = 3701). MetS was considered as main endpoint. Weighted multivariable logistic regression models showed that high cotinine level (≥ 0.05 ng/mL) was associated with increased odds of MetS [odds ratio = 1.54, 95% confidence interval: 1.01, 2.36], and the association between Zn intake levels and MetS did not demonstrate statistical significance. Importantly, the multiplicative interaction term between low Zn intake (≤ 4.89 mg/1000 kcal) and high cotinine level was related to higher odds of MetS (p-value for interaction 0.018). For the group with low Zn intake, high cotinine level was associated with increased odds of MetS. However, there was no significant relationship between cotinine levels and MetS risk in the group with high Zn intake. The effect modification by Zn intake on the relationship of tobacco smoke exposure and risk of MetS is significant in individuals who had a sedentary time of ≥ 6 h, identified as non-Hispanic White, or resided in households with smokers. In short, low Zn intake may potentiate the association of tobacco smoke exposure and MetS risk in children and adolescents.

Secondhand smoke exposure can increase the risk of first ischemic stroke: A 10.7-year prospective cohort study in China.

INTRODUCTION: Passive smoking is considered a major public health issue in China. Prospective evidence regarding the link between secondhand smoke (SHS) and ischemic stroke in China is scarce. METHODS: The China Kadoorie Biobank (CKB) study in Liuzhou City recruited 50,174 participants during 2004-2008. Of these 30,456 never-smokers were included in our study. The median follow-up period was 10.7 years. The incidence of ischemic stroke was obtained through the China Disease Surveillance Points (DSP) system and the Health Insurance (HI) database. Cox proportional risk models were used to evaluate the association between SHS exposure and ischemic stroke. RESULTS: During 320,678 person-years of follow-up, there were 2059 patients with ischemic stroke observed and the incidence of ischemic stroke was 6.42 per thousand person-years. Participants exposed to SHS daily faced a 21 % higher risk of ischemic stroke (HR = 1.21, 95 %CI: 1.09-1.34) compared to those exposed to SHS less than once a week. Subgroup analyses revealed that daily SHS exposure was linked to heightened risk of ischemic stroke among women, non-employed, and non-weekly tea drinkers. CONCLUSIONS: Daily SHS exposure was associated with higher risks of ischemic stroke. Proactive tobacco control strategies are necessary to decrease the risk of ischemic stroke in never smokers.

The Association of Tobacco Smoking and Level of Apoptosis in the Long Head of the Biceps Chronic Tendinopathy-An Immunohistochemical Study.

BACKGROUND: The substances present in cigarette smoke have a negative impact on cellular integrity and metabolism, can reduce blood flow to tissues, and can disrupt collagen synthesis. Ultimately this can lead to cell death, which clinically may result in impaired tendon healing and the onset of chronic tendinopathy. Within the shoulder, the exact association between the extent of apoptosis in the long head of the biceps (LHB) tendon and harmful factors like cigarette smoke remains unclear. OBJECTIVES: The purpose of this study was to investigate the connection between smoking, the degree of apoptosis in LHB tendinopathy, and the long-term outcomes of surgical treatment. DESIGN: Observational, retrospective study. METHODS: This study included 22 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHB tendinopathy with or without concomitant rotator cuff tears (RCT). The intra-articular LHB tendon remnants were histologically examined by measuring the level of expression of apoptotic cell markers such as BCL2, cleaved caspase 3, and p53. Pre- and postoperative clinical outcomes were analyzed by collecting patient report outcome measures such as the American Shoulder and Elbow Surgeons (ASES) score and the Visual Analogue Scale (VAS) for pain. RESULTS: The smokers group had a mean pack-year history of 13.12 (SD = 9.94), mean number of cigarettes per day of 14.77 (SD = 4.64), and a mean smoking duration of 16.38 (SD = 10.1) years. Among the smoking indexes, the number of cigarettes per day showed a positive correlation with Snyder classification (p = 0.0459, rho = 0.3682). Non-smokers and smokers did not show a statistically significant difference in the expression indexes of BCL2, cleaved caspase 3, or p53 (p = 0.4216, p = 0.5449, p = 0.5613, respectively). However, the cleaved caspase 3 expression index showed a negative correlation with the severity of rotator cuff lesions in the total population (p = 0.0193, rho = -0.4651). CONCLUSIONS: While apoptotic processes in the LHB tendon were observed, no significant association was found between tobacco smoking, the extent of apoptosis, and clinical outcomes. However, the expression of the apoptotic marker cleaved caspase 3 correlated with the severity of rotator cuff pathology. Furthermore, active smoker status was associated with worse clinical outcomes in terms of pain following LHB tenodesis or tenotomy.

The association between passive smoking and sleep quality in a Chinese hypertensive population: A cross-sectional study.

INTRODUCTION: This study evaluates the association between passive smoking, specifically secondhand smoke (SHS) and thirdhand smoke (THS) exposure, and sleep quality in a hypertensive population. METHODS: We enrolled 1427 eligible hypertensive patients from a 2022 national cross-sectional survey in China. Data on tobacco smoke exposure and sleep were collected via questionnaires. Multiple logistic regression and linear regression were employed to assess the relationship between passive smoking and sleep quality characteristics, as well as the correlation between passive smoking exposure characteristics and sleep quality. RESULTS: Among 589 hypertensive patients with no tobacco smoke exposure, 679 exposed to SHS, and 159 exposed to THS, SHS exposure was associated with a higher risk of poor sleep quality, even after adjusting for potential confounding factors (ß=0.10; 95% CI: 0.32-0.95). No significant relationship was observed between THS exposure and sleep quality. SHS exposure was associated with various sleep quality characteristics, including shorter sleep duration (AOR=1.71; 95% CI: 1.06-2.76) and increased frequency of 1-2 sleep disturbances per week (AOR=1.68; 95% CI: 1.25-2.26). Individuals exposed to SHS were more likely to experience poorer subjective sleep quality (AOR=1.53; 95% CI: 1.07-2.21) and have sleep efficiency <65% (AOR=1.82; 95% CI: 1.22-2.71). Exposure to passive smoking at home, in the community, in public places, exposure to passive smoking with family and friends, and increased frequency of exposure, were all associated with a higher risk of poor sleep quality. CONCLUSIONS: Our study suggests that SHS exposure in hypertensive populations is associated with poor sleep quality and various characteristics of sleep quality. No significant association was found between THS exposure and sleep quality. These findings underscore the need to enhance tobacco control efforts in China, particularly for individuals with chronic diseases, to safeguard public health.

Exposure to household secondhand tobacco smoke and the odds of developing atopic dermatitis among adolescents: A causal mediation analysis.

INTRODUCTION: Exposure to household secondhand tobacco smoke (SHS) among adolescents has been shown to be associated with atopic dermatitis, and affects disproportionality females. However, the mechanisms underlying this link are uncertain. This study sought to identify modifiable factors that mediate the relationship between household SHS exposure and atopic dermatitis among adolescents. METHODS: During October 2015, a cross-sectional study was conducted using the ISAAC questionnaire for data collection from adolescents enrolled in nine high schools of Hawalli - one of the six governorates of Kuwait. Data were collected on sociodemographic characteristics, self-reported tobacco smoking among adolescents, household SHS exposure (≥1 smokers at home vs none), self-reported asthma and atopic dermatitis. For causal mediation analysis an inverse odds-weighting approach was used. RESULTS: Of 746 participants, 74.8% were Kuwaiti, 50.1% were female, 12.4% were regular daily smokers and 54.1% had household SHS exposure, which was more common among Kuwaiti (79.6%) than non-Kuwaiti (20.4%) adolescents. The prevalences of self-reported asthma and atopic dermatitis were 20.6% and 14.9%, respectively. After adjusting for the pre-exposure covariates (i.e. sex and nativity), household SHS exposure had a significant (p=0.043) total effect, non-significant (p=0.133) natural direct effect, and marginally insignificant (p=0.058) natural indirect effect, which were jointly mediated by asthma status and adolescent's self-reported smoking status, with a proportion of mediated risk to atopic dermatitis of 29.6%. CONCLUSIONS: Asthma and self-tobacco smoking among adolescents not only directly affected but also mediated household SHS exposure effect on atopic dermatitis risk. Voluntarily adopting a smoke-free home rule may minimize household SHS exposure, reduce the odds of developing asthma, and deter the initiation of tobacco smoking among adolescents. Such an effort will likely mitigate the atopic dermatitis risk among adolescents in this and other similar settings. If implemented, future studies may contemplate evaluating the impact of such intervention.

Association between secondhand smoke exposure and incident heart failure: The Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: There are no studies on the association between secondhand smoke (SHS) exposure and incident heart failure (HF). This cohort study aimed to examine the associations of self-reported and urinary cotinine-assessed SHS exposure with incident HF. METHODS AND RESULTS: This study included 5548 non-active smoking participants aged 45-84 years and free of known cardiovascular diseases and HF at baseline who self-reported SHS exposure time in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000-2002). A cohort subset of 3376 non-active smoking participants underwent urinary cotinine measurements. HF events were verified by medical records or death certificates and ascertained from baseline through 2019. Multivariable Cox proportional hazards regression analysis was used with adjustment for demographic variables, traditional cardiovascular risk factors, physical activity, tobacco pack-years and medications. During a median follow-up of 17.7 years, 353 and 196 HF events were identified in the self-report cohort and cohort subset, respectively. In the self-report cohort, compared with the SHS unexposed group (0 h/week), the highest tertile of the SHS exposed group (7-168 h/week) was not associated with incident HF (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-1.00; p = 0.052). In contrast, in the cohort subset, participants with detectable urinary cotinine >7.07 ng/ml had a higher risk of incident HF than those with undetectable urinary cotinine ≤7.07 ng/ml (HR 1.45, 95% CI 1.03-2.06; p = 0.034). There were no significant heterogeneities in HF risk by age, sex, race/ethnicity, or past smoking status. CONCLUSION: Secondhand smoke exposure reflected by modestly increased urinary cotinine (>7.07 ng/ml) rather than self-report in non-active smokers was associated with a 40-50% higher risk of any HF event.

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model.

Tobacco smoke (TS) is the leading cause for lung cancer (LC), and female smokers are at a greater risk for LC. Yet, the underlying causes are unknown. We performed whole genome scans in TS exposed wild type and histologically characterized tumor lesions of cRaf transgenic mice. We constructed miRNA-gene and transcription factor-miRNA/gene regulatory networks and determined sex-specific gene regulations by evaluating hormone receptor activities. We validated the findings from TS exposed cRaf mice in a large cohort of smoking and never-smoking LC patients. When compared to males, TS prompted a sevenfold increase in tumor multiplicity in cRaf females. Genome-wide scans of tumor lesions identified 161 and 53 genes and miRNAs, which code for EGFR/MAPK signaling, cell proliferation, oncomirs and oncogenes, and 50% of DEGs code for immune response and tumor evasion. Outstandingly, in transgenic males, TS elicited upregulation of 20 tumor suppressors, some of which are the targets of the androgen and estrogen receptor. Conversely, in females, 18 tumor suppressors were downregulated, and five were specifically repressed by the estrogen receptor. We found TS to perturb the circadian clock in a sex-specific manner and identified a female-specific regulatory loop that consisted of the estrogen receptor, miR-22-3p and circadian genes to support LC growth. Finally, we confirmed sex-dependent tumor promoting effects of TS in a large cohort of LC patients. Our study highlights the sex-dependent genomic responses to TS and the interplay of circadian clock genes and hormone receptors in the regulation of oncogenes and oncomirs in LC growth.