Secondhand Smoke Exposure Timing Triggers Distinct Placental Responses in Mouse Pregnancy

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major pregnancy complications that are linked to placental dysfunction and environmental stimulation such as the use of electronic cigarettes (eCig). This study investigates the molecular impacts of timed eCig exposure in a C57BL/6 mouse model of PE and IUGR using bulk RNA-sequencing of placental tissues. Pregnant mice were exposed to eCig vapor via nose-only system starting at embryonic day 12.5 (eCig-6d, before spiral artery (SA) invasion) or 14.5 (eCig-4d, after SA invasion) until E18.5 (necropsy), with healthy controls exposed to room air (n = 6/group). The eCig-4d group developed PE, whereas the eCig-6d group developed both PE and IUGR. RNA-seq analysis revealed 429 differentially expressed genes (DEGs) in eCig-4d (IUGR-like) group and 64 DEGs in eCig-6d (PE + IUGR-like) group compared to controls. Pathway and gene network analyses indicated that eCig-4d exposure activated NF-κB–driven inflammation, suppressed ECM organization and collagen biosynthesis, and downregulated vasoactive genes/mitochondrial-associated genes (NOS1/2), accompanied by impaired complement initiation and reduced both macrophage and monocyte signals. Similarly, eCig-6d exposure led to downregulation of complement-associated genes and granule-related components, possibly implicating weakened neutrophil responsiveness and compromised inflammatory resolution at the maternal–fetal interface. Our findings align with prior studies on physiological dysfunctions in PE and IUGR, while also providing novel insights into the temporally specific cellular responses induced by eCig exposure.

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS+semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P≤0.0001) and placental weight (1.13-fold, P≤0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P≤0.05), JNK (2.4-fold, P≤0.05) and p38 (2.1-fold, P≤0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P≤0.05) and IL-1β (1.03-fold, P≤0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P<0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.

Introduction: Due to the high prevalence of smoking in China, exposure to second hand smoke (SHS) is a serious public health issue. However, school-aged children’s behavioral responses to SHS exposure and the associated factors are unclear. Aims: This study aims to (a) identify the sources and settings of SHS exposure among school-aged sick children and their mothers in Guangzhou, China; (b) describe the behavioral responses of those children and mothers when exposed to SHS; and (c) examine the personal and environmental factors associated with children’s responses to SHS exposure. Methods: Qualitative and quantitative methods were combined in this study. Forty-five in-depth individual interviews were conducted to investigate sick school-aged children and their mothers’ understanding of and responses to SHS. A pilot survey was used to assess the validity and reliability of the questionnaire and the feasibility of the study. A cross-sectional survey was conducted with the children and their mothers at three hospitals in Guangzhou in 2012. All sick children who were aged 6 to 12 years, able to communicate in Mandarin Chinese, and not acutely or severely ill, along with their nonsmoking mothers, were invited to join this study. Results: A total of 339 pairs of sick children and their mothers were included in the data analysis. Of these pairs, 169 (49.9%) lived with smokers. All sick children and their mothers experienced high-level SHS and third hand smoke (THS) exposure inside or outside the home. Those living with nonsmokers were also at risk of household SHS and THS exposure from guests. Most of the sick school-aged children were unaware of the dangers of SHS and THS, while the mothers had a better understanding of SHS and THS. The majority of children would adopt self-protective behaviors when exposed to SHS. The regression model for children’s behavioral responses to SHS exposure by family smokers found two significant factors: amount of social support and family smoke-free policy. Five factors were associated with children’s behavioral responses to SHS exposure by guest smokers, including boys, living with smokers, amount of social support, family members informed of the dangers of smoking, and fathers protecting children from SHS. The amount of social support, and fathers protecting children from SHS were also associated with children’s behavioral responses to SHS exposure by stranger smokers. Conclusions: To our knowledge, this is the first study to describe self-protective behavioral responses to SHS exposure among sick school-aged children in mainland China and the personal and environmental factors associated with these responses. Boys, living with smokers, and a partial smoke-free policy at home were negatively related to children’s responses to SHS exposure; however, more information about smoking, fathers’ protection from SHS, and information about the harms of smoking by family members were associated with greater self-protection among sick school-aged children. Therefore, multiple-direction interventions should be considered for children’s health promotion about smoking and SHS.

Apoptosis is critical in placental development, and its dysregulation is linked to pregnancy complications such as intrauterine growth restriction (IUGR) and preeclampsia (PE). Environmental exposures, particularly secondhand smoke (SHS) and e-cigarettes (eCigs), may contribute to placental dysfunction through apoptotic pathways. This study examined the effects of SHS and eCig exposure on placental apoptosis and growth-regulatory proteins in a murine model. C57BL/6 pregnant mice were exposed to SHS or eCigs at two critical gestational time points: early trophoblast invasion (E12.5 to E18.5) and established invasion (E14.5 to E18.5). Placental tissues were collected and analyzed for pro-apoptotic and anti-apoptotic markers, heat shock proteins, insulin-like growth factor-binding proteins (IGFBPs), and growth regulators. SHS exposure increased pro-apoptotic markers (BAD, Fas/FasL) and decreased mitochondrial function markers (cytochrome c), indicating compromised cellular survival. Both SHS and eCig exposure reduced anti-apoptotic markers (BCL-2, HSP27, survivin) and growth regulators (IGF-1, IGFBPs). SHS and eCig exposure create a pro-apoptotic environment in the placenta, potentially impairing fetal development through altered apoptotic and growth-regulatory pathways. These findings underscore the risks of environmental exposures during pregnancy, highlighting the need for strategies to minimize maternal exposure to SHS and eCigs.

A history of second hand smoke exposure: are we asking the right questions?

Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights leading to the development of intrauterine growth restriction (IUGR) in mice. Hypertension and proteinuria are two important hallmarks of obstetric pathology leading to the development of preeclampsia (PE). In the present study, we wanted to determine the effects SHS exposure at two different important gestational points during mouse pregnancy. C57/Bl6 mice were exposed to SHS via a nose-only delivery system (Scireq) for 4 days (from 14.5 gestational day (dGA) to 17.5 dGA) or for 6 days (from 12.5 dGA to 17.5 dGA). At the time of necropsy (18.5 dGA) placental and fetal weights were recorded. Maternal blood pressure was determined with a tail occlusion cuff (Kent Scientific) and dip stick test for proteinuria was obtained. Treatment with SHS showed: 1) a significant decrease in placental weight (p&lt;0.0001) and fetal weight (p&lt;0.0002) following 4 days of exposure, 2) higher systolic (p&lt;0.02) and diastolic (p&lt;0.02) blood pressure following 6 days of exposure, and 3) increased proteinuria after 6 days of exposure. We conclude that detrimental effects of SHS coincides with the length of maternal exposure. We confirmed that 4 days of exposure resulted in metrics common to IUGR while 6 days of exposure more closely resembled PE pathology. These results could be beneficial in understanding the long-term effects of SHS exposure and the development of placental diseases. NIH 1R15HD108743 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background No study has reported the relationship between secondhand smoke (SHS) exposure and new-onset hypertension (NOHT) in self-reported never-smokers verified by cotinine. Purpose This longitudinal study was conducted to evaluate whether the change of SHS exposure status at baseline and at follow-up affects NOHT in self-reported and cotinine-verified never-smokers. Methods Out of individuals enrolled in the Kangbuk Samsung Cohort study (KSCS) between 2012 and 2016, 65,169 self-reported and cotinine-verified never-smokers without hypertension at baseline visit (20,046 men; age 36±5.7 years) were included. The mean follow-up period in this study was 32 months (6–58 months). SHS exposure was defined as having experienced passive smoking indoors at home or the workplace. Individuals were divided into 4 groups on the basis of their SHS exposure status at baseline and at follow-up: no SHS exposure group (Group I) as individuals without SHS exposure both at baseline and at follow-up; new SHS exposure group (Group II) as those without SHS exposure at baseline and with SHS exposure at follow-up; ex-SHS exposure group (Group III) as those with SHS exposure at baseline and without SHS exposure at follow-up; continuous SHS exposure group (Group IV) as those with SHS exposure both at baseline and at follow-up. New-onset hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, or current use of antihypertensive medication(s) at follow-up. Results The incidence of NOHT in the overall population was 2.5%; the incidence in group I, II, III, and IV was 2.3%, 3.2%, 2.9%, and 3.1%, respectively (p&amp;lt;0.001). The results in a multivariate Cox-hazard model adjusted for the baseline variables including age, sex, body mass index, waist circumference, vigorous exercise, alcohol consumption and presence of diabetes showed that Group II and IV increased relative risks (RRs) for NOHT compared to Group I (RR[95% CI], 1.44 [1.17, 1.77] for Group II and 1.21 [1.01, 1.45] for Group IV) However, Group III did not increase the risk of NOHT (0.95 [0.83, 1.08]). In another model adjusted for the variables in the above model and creatinine, uric acid, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and high-sensitivity C reactive protein showed that only Group II increased the risk for NOHT (1.43 [1.16, 1.77] in Group II, 0.94 [0.82, 1.07] in Group III, 1.18 [0.98, 1.41] in Group IV). Conclusions This study showed that the new and continuous SHS exposure, but not ex-SHS exposure, increased the risk for NOHT in self-reported never-smokers verified as nonsmokers by urinary cotinine. In particular, the relationship to increased risk for NOHT was more obvious in individuals with new SHS exposure than in those with continuous SHS exposure. These findings suggest that it is important to continuously minimize SHS exposure and prohibit smoking at home and at workplace to reduce the risk of developing hypertension. Funding Acknowledgement Type of funding source: None

7633 Background: The presence of EGFR mutations in NSCLC has strongly associated with never-smoking history. SHS exposure is associated with higher risk of lung cancer. We have conducted this study to evaluate the association between SHS exposure and likelihood of mutations in EGFR gene in NSCLC patients who had never smoked. Methods: SHS exposure information from a total of 93 never smokers (&lt;100 lifetime cigarettes) with newly diagnosed primary NSCLC was obtained using a standardized questionnaire. Patients were asked whether they were regularly exposed to SHS at home or work places, respectively. Nucleotide sequencing of the kinase domain of EGFR (exons 18 to 21) was performed using nested PCR amplification of individual exons. Results: Patient characteristics (n=93) included median age 57 years; female (n= 81); adenocarcinoma ± bronchoalveolar carcinoma (n= 82); EGFR mutation (1 mutation in exon 18 G719, 31 in-frame deletions in exon 19, 10 mutations in codon 858 in exon 21). Fifty-two (55.9%) of the patients reported having been exposed to SHS, including 46 (49.5%) exposed at home and 13 (14.0%) exposed at work. The incidence of EGFR mutations was not associated with female gender and adenocarcinoma histology. Patients with SHS exposure showed a trend towards lower incidence of EGFR mutations (36.5% vs. 56.1%, P= 0.060) and a significantly lower incidence of deletion mutations in exon 19 (57.9% vs. 87.0%, P= 0.033). When the incidence of EGFR mutations was compared, no difference between SHS exposure at home and work places was found. No significant differences were found for other clinicopathological factors according to SHS exposure. Conclusions: Our results indicate weak evidence of relationship between likelihood of mutation in EGFR gene and SHS exposure. The deletion mutations in exon 19 were significantly less common in patients with SHS exposure. No significant financial relationships to disclose.

Exposure to secondhand smoke (SHS) during fetal development results in negative postnatal effects, including altered organ development, changes in metabolism, and increased risk of respiratory illness. Previously, we found the induction of intrauterine growth restriction (IUGR) dependent on the expression of the receptor for advanced glycation end-products (RAGE) in mice treated with SHS. Furthermore, antenatal SHS exposure increases RAGE expression in the fetal lung. Our objective was to determine the postnatal effects of antenatal SHS treatment in 4- and 12-week-old offspring. Pregnant animals were treated with SHS via a nose-only delivery system (Scireq Scientific, Montreal, Canada) for 4 days (embryonic day 14.5 through 18.5), and offspring were evaluated at 4 or 12 weeks of age. Animal and organ weights were measured, and lungs were histologically characterized. Blood pressure and heart rates were obtained, and RAGE protein expression was determined in the lungs of control and treated animals. We observed the following: (1) significant decreases in animal, liver, and heart weights at 4 weeks of age; (2) increased blood pressure in 4-week-old animals; and (3) increased RAGE expression in the lungs of the 4-week-old animals. Our results suggest an improvement in these metrics by 12 weeks postnatally such that measures were not different regardless of RA or SHS exposure. Increased RAGE expression in lungs from 4-week-old mice antenatally treated with SHS suggests a possible role for this important smoke-mediated receptor in establishing adult disease following IUGR pregnancies.

Background:Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3–4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline.Objective:The goal of this study was to assess the effects of chronic SHS exposure (10 months’ exposure to ) on behavioral and cognitive function, metabolism, and neuropathology in mice.Methods:Wild-type (WT) and htau female and male mice were exposed to SHS (90% side stream, 10% main stream) using the SCIREQ® inExpose™ system or air control for 168 min per day, for 312 d, 7 d per week. The exposures continued during the days of behavioral and cognitive testing. In addition to behavioral and cognitive performance and neuropathology, the lungs of mice were examined for pathology and alterations in gene expression.Results:Mice exposed to chronic SHS exposure showed the following genotype-dependent responses: a) lower body weights in WT, but not htau, mice; b) less spontaneous alternation in WT, but not htau, mice in the Y maze; c) faster swim speeds of WT, but not htau, mice in the water maze; d) lower activity levels of WT and htau mice in the open field; e) lower expression of brain PHF1, TTCM1, , and HSP90 protein levels in WT male, but not female, mice; and f) more profound effects on hippocampal metabolic pathways in WT male than female mice and more profound effects in WT than htau mice.Discussion:The brain of WT mice, in particular WT male mice, might be especially susceptible to the effects of chronic SHS exposure. In WT males, independent pathways involving ascorbate, flavin adenine dinucleotide, or palmitoleic acid might contribute to the hippocampal injury following chronic SHS exposure. https://doi.org/10.1289/EHP8428

Normal pregnancy involves extensive remodeling of uterine and spiral arteries and matrix metalloproteinases (MMPs)-mediated proteolysis of extracellular matrix (ECM). Preeclampsia is characterized by hypertension in pregnancy (HTN-Preg) and intrauterine growth restriction (IUGR) with unclear mechanisms. Initial faulty placentation and reduced uterine perfusion pressure (RUPP) could release cytoactive factors and trigger an incessant cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent and depth of uterine vascularization and the proteolytic enzymes and ECM proteins involved are unclear. We hypothesized that HTN-Preg involves decreased uterine vascularization and arterial remodeling by MMPs and accumulation of ECM collagen. Blood pressure (BP) and fetal parameters were measured in normal Preg rats and RUPP rat model, and the uteri were assessed for vascularity, MMP levels, and collagen deposition. On gestational day 19, BP was higher, and the uterus weight, litter size, and pup weight were reduced in RUPP vs. Preg rats. Histology of uterine tissue sections showed reduced number (5.75 ± 0.95 vs. 11.50 ± 0.87) and size (0.05 ± 0.01 vs. 0.12 ± 0.02 mm2) of uterine spiral arterioles in RUPP vs. Preg rats. Immunohistochemistry showed localization of endothelial cell marker cluster of differentiation 31 (CD31) and smooth muscle marker α-actin in uterine arteriolar wall and confirmed decreased number/size of uterine arterioles in RUPP rats. The cytotrophoblast marker cytokeratin-7 showed less staining and invasion of spiral arteries in the deep decidua of RUPP vs. Preg rats. Uterine arteries showed less expansion in response to increases in intraluminal pressure in RUPP vs. Preg rats. Western blot analysis, gelatin zymography, and immunohistochemistry showed decreases in MMP-2 and MMP-9 and increases in the MMP substrate collagen-IV in uterus and uterine arteries of RUPP vs. those in Preg rats. The results suggest decreased number, size and expansiveness of spiral and uterine arteries with decreased MMP-2 and MMP-9 and increased collagen-IV in HTN-Preg. Decreased uterine vascularization and uterine arterial expansive remodeling by MMPs could be contributing mechanisms to uteroplacental ischemia in HTN-Preg and preeclampsia.NEW & NOTEWORTHY Preeclampsia is a pregnancy-related disorder in which initial inadequate placentation and RUPP cause the release of cytoactive factors and trigger a ceaseless cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent/depth of uterine vascularization and the driving proteolytic enzymes and ECM proteins are unclear. This study shows decreased number, size, and expansiveness of uterine spiral arteries, with decreased MMP-2 and MMP-9 and increased collagen-IV in HTN-Preg rats. The decreased uterine vascularization and uterine arterial expansive remodeling by MMPs could contribute to progressive uteroplacental ischemia in HTN-Preg and preeclampsia.

Secondhand smoke (SHS) exposure during pregnancy is linked to adverse birth outcomes, such as low birth weight and preterm birth. While questionnaires are commonly used to assess SHS exposure, their ability to capture true exposure can vary, making it difficult for researchers to harmonize SHS measures. This study aimed to compare self-reported SHS exposure with measurements of airborne SHS in personal samples of pregnant women. SHS was measured on 48-hour integrated personal PM2.5 Teflon filters collected from 204 pregnant women, and self-reported SHS exposure measures were obtained via questionnaires. Descriptive statistics were calculated for airborne SHS measures, and analysis of variance tests assessed group differences in airborne SHS concentrations by self-reported SHS exposure. Participants were 81% Hispanic, with a mean (standard deviation [SD]) age of 28.2 (6.0) years. Geometric mean (SD) personal airborne SHS concentrations were 0.14 (9.41) µg/m3. Participants reporting lower education have significantly higher airborne SHS exposure (p = .015). Mean airborne SHS concentrations were greater in those reporting longer duration with windows open in the home. There was no association between airborne SHS and self-reported SHS exposure; however, asking about the number of smokers nearby in the 48-hour monitoring period was most correlated with measured airborne SHS (Two + smokers: 0.30 µg/m3 vs. One: 0.12 µg/m3 and Zero: 0.15 µg/m3; p = .230). Self-reported SHS exposure was not associated with measured airborne SHS in personal PM2.5 samples. This suggests exposure misclassification using SHS questionnaires and the need for harmonized and validated questions to characterize this exposure in health studies. This study adds to the growing body of evidence that measurement error is a major concern in pregnancy research, particularly in studies that rely on self-report questionnaires to measure SHS exposure. The study introduces an alternative method of SHS exposure assessment using objective optical measurements, which can help improve the accuracy of exposure assessment. The findings emphasize the importance of using harmonized and validated SHS questionnaires in pregnancy health research to avoid biased effect estimates. This study can inform future research, practice, and policy development to reduce SHS exposure and its adverse health effects.

ObjectivesThis study was conducted to assess the prevalence of tobacco use, secondhand smoke (SHS) exposure and knowledge about SHS and third-hand smoke (THS) exposure among students in a medical college...

Passive smoking exposure is a topic of great concern for public health because of its well-known adverse effects on human health (International Agency for Research on Cancer 2004). Two news articles on this topic were published in the February 2011 issue of Environmental Health Perspectives (Burton 2011; Lubick 2011). Lubick (2011) discussed the global health burden of secondhand smoke, and Burton (2011) emphasized a new and alarming consequence of smoking in indoor environments—“thirdhand smoke”—a term first coined in 2006 (Szabo 2006). Secondhand smoke is defined as “the combination of smoke emitted from the burning end of a cigarette or other tobacco products and smoke exhaled by the smoker” (World Health Organization 2007). Thus, secondhand smoke exposure consists of an unintentional inhalation of smoke that occurs close to people smoking and/or in indoor environments where tobacco was recently used. Thirdhand smoke is a complex phenomenon resulting from residual tobacco smoke pollutants that adhere to the clothing and hair of smokers and to surfaces, furnishings, and dust in indoor environments. These pollutants persist long after the clearing of secondhand smoke. They are reemitted into the gas phase or react with oxidants or other compounds present in the environment to form secondary contaminants, some of which are carcinogenic or otherwise toxic for human health (Matt et al. 2011). Thus, thirdhand smoke exposure consists of unintentional intake (mainly through inhalation but also via ingestion and dermal routes) of tobacco smoke and other related chemicals that occurs in the absence of concurrent smoking. Exposure can even take place long after smoking has ceased, through close contact with smokers and in indoor environments in which tobacco is regularly smoked. Lubick (2011) considers secondhand smoke synonymous with passive smoking, as do the majority of the authors publishing on this topic. However, in light of new evidence about thirdhand smoke (Matt et al. 2011), it is no longer appropriate to use the term “secondhand smoke” as a synonym for passive smoking or environmental tobacco smoke, because it represents a pars pro toto. In other words, using the term “secondhand smoke” mistakes one part of the problem for the whole. Instead, we propose that “passive smoking” or “environmental tobacco smoke” be used as a more inclusive term to describe any tobacco smoke exposure outside of active smoking. This question of terminology is of particular concern for researchers evaluating passive smoking exposure in indoor settings, especially in domestic environments. Since numerous countries have introduced smoking bans in enclosed public places, domestic environments have become the main sources of passive smoking exposure (World Health Organization 2007). We believe researchers should determine the independent contributions of secondhand and thirdhand smoke when they assess the magnitude of pollutant intake due to passive smoking exposure.

Cadmium (Cd), a carcinogenic metal also related to reproductive and cardiovascular diseases, is contained in tobacco and elevated concentrations of it in humans have been consistently associated with first-hand tobacco smoke; however, there is scarce and inconclusive evidence of the relationship between Cd and secondhand smoke (SHS) exposure. Our aim was to evaluate the association between exposure to tobacco, both active and SHS, with urinary Cd concentrations in Mexican women. In a cross-sectional analysis that included 998 women living in northern Mexico, we measured the concentration of creatinine-adjusted urinary Cd (µg-cadmium/g-creatinine) using inductively coupled plasma triple quadrupole (ICP-QQQ) in tandem mass spectrometry mode (MS/MS). We gathered tobacco smoking information through an in-person interview and formed seven groups: non-smokers without SHS exposure; non-smokers with SHS exposure; ex-smokers without SHS exposure <1 year of quitting; ex-smokers without SHS exposure ≥1 year of quitting, ex-smokers with SHS exposure <1 year of quitting; ex-smokers with SHS exposure ≥1 year of quitting and current smokers. The interview also yielded sociodemographic characteristics. We used linear multivariable regression models to estimate the association between Cd concentrations and tobacco smoke exposure. Compared to non-smokers without SHS exposure, we found higher Cd concentrations in ex-smokers with SHS exposure <1 year of quitting and current smokers (adjusted geometric means 0.51 vs. 1.01 and 0.69 µg-cadmium/g-creatinine, respectively). Our results do not support a conclusion that SHS exposure is a source of Cd body burden.