The Sulfotransferase SULT1C2 Is Epigenetically Activated and Transcriptionally Induced by Tobacco Exposure and Is Associated with Patient Outcome in Lung Adenocarcinoma

Lung cancer is the leading cause of cancer-related death. Tobacco exposure is associated with 80–90% of lung cancer cases. The SULT1C2 sulfotransferase modifies xenobiotic compounds to enhance secretion but can also render these compounds carcinogenic. To determine if SULT1C2 contributes to tobacco-related carcinogenesis in the lung, we analyzed the expression and epigenetic state of SULT1C2 in human lung adenocarcinoma (LUAD) samples and in LUAD cell lines exposed to cigarette smoke condensate (CSC). SULT1C2 expression was significantly positively correlated to overall LUAD patient survival in smokers, was elevated in LUAD tumors compared to adjacent non-tumor lung, and was significantly correlated with levels of patient exposure to tobacco smoke. SULT1C2 promoter DNA methylation was inversely correlated with expression in LUAD, and hypomethylation of the SULT1C2 promoter was observed in Asian patients, as compared to Caucasians. In vitro analysis of LUAD cell lines indicates that CSC stimulates expression of SULT1C2 in a dose-dependent and cell-line-specific manner. In vitro methylation of the SULT1C2 promoter significantly decreased transcriptional activity of a reporter plasmid, and SULT1C2 expression was activated by the DNA demethylating agent 5-Aza-2′-deoxycytidine in a cell line in which the SULT1C2 promoter was hypermethylated. An aryl hydrocarbon receptor (AHR) binding site was detected spanning critical methylation sites upstream of SULT1C2. CSC exposure significantly increased AHR binding to this predicted binding site in the SULT1C2 promoter in multiple lung cell lines. Our data suggest that CSC exposure leads to activation of the AHR transcription factor, increased binding to the SULT1C2 promoter, and upregulation of SULT1C2 expression and that this process is inhibited by DNA methylation at the SULT1C2 locus. Additionally, our results suggest that the level of SULT1C2 promoter methylation and gene expression in normal lung varies depending on the race of the patient, which could in part reflect the molecular mechanisms of racial disparities seen in lung cellular responses to cigarette smoke exposure.

Moraxella-dominated pediatric nasopharyngeal microbiota associate with upper respiratory infection and sinusitis

Background Distinct bacterial upper airway microbiota structures have been described in pediatric populations, and relate to risk of respiratory viral infection and, exacerbations of asthma. We hypothesized that distinct nasopharyngeal (NP) microbiota structures exist in pediatric populations, relate to environmental exposures and modify risk of acute sinusitis or upper respiratory infection (URI) in children. Methods Bacterial 16S rRNA profiles from nasopharyngeal swabs (n = 354) collected longitudinally over a one-year period from 58 children, aged four to seven years, were analyzed and correlated with environmental variables, URI, and sinusitis outcomes. Results Variance in nasopharyngeal microbiota composition significantly related to clinical outcomes, participant characteristics and environmental exposures including dominant bacterial genus, season, daycare attendance and tobacco exposure. Four distinct nasopharyngeal microbiota structures (Cluster I-IV) were evident and differed with respect to URI and sinusitis outcomes. These clusters were characteristically either dominated by Moraxella with sparse underlying taxa (Cluster I), comprised of a non-dominated, diverse microbiota (Cluster II), dominated by Alloiococcus/Corynebacterium (Cluster III), or by Haemophilus (Cluster IV). Cluster I was associated with increased risk of URI and sinusitis (RR = 1.18, p = 0.046; RR = 1.25, p = 0.009, respectively) in the population studied. Conclusion In a pediatric population, URI and sinusitis associate with the presence of Moraxella-dominated NP microbiota.

Association between Tobacco and Tuberculosis: A short narrative review

Tobacco use increases the risk of contracting tuberculosis (TB), and blights the response to treatment of the disease. Although Links between Tobacco and TB have long been suspected, still many Indian patients continue to use tobacco. Our goal is to couple reviews of older and new research to provide definitive evidence of this dangerous connection so as to put an end to the TB epidemic.: Search of studies with English language abstract published between 2000 to June 2020 was undertaken in Google Scholar and PubMed. Search included the use of keywords “tobacco” with “tuberculosis,” “cessation,” or ‘’Tuberculosis Control Programme’’. Reference lists of the articles were examined for other relevant titles that included effective estimates of tobacco exposure in relation to tuberculosis outcomes.: Available evidence shows a strong association between tobacco and tuberculosis. People who use tobacco unknowingly put themselves at high risk of getting this disease. Reduction in the prevalence of tobacco use is urgent to bring about collateral benefits in the control of the TB problem.It is high time that TB control programs must begin to address tobacco control. Within the healthcare system opportunities must be created to provide encouragement for the TB patients so that it is easier for them to overcome this addiction.There urgent need for research in the field of tobacco and tuberculosis so as to reduce the burden of tuberculosis in India.

Decreased Levels of Soluble CD44 in a High-Risk Population following a Smoking Cessation Program

Tobacco is a risk factor of head and neck cancer (HNC) and smoking cessation alone may reduce HNC risk by 70%. Soluble CD44 (solCD44), a cell surface receptor linked to cell proliferation and migration, and total protein (TP) levels can detect early HNC. This study aims to determine whether salivary solCD44 and TP levels in oral rinses change following a smoking cessation program. 150 smokers provided oral rinse samples at baseline and at a 12-month follow-up after participation in a smoking cessation program. Assays to measure levels of solCD44, TP, and cotinine, a metabolite used as a biomarker of tobacco exposure, were completed. A paired-samples t-test was used to determine whether there was a statistically significant (p < 0.05) mean difference in biomarker levels before and after the program. Baseline and at 12-month follow-up data were available for 88 subjects, 21 of whom quit smoking entirely. Mean levels of solCD44 significantly decreased by 0.412 ng/mL from baseline to the 12-month follow-up, p = 0.010. There was no significant difference in mean TP levels, p = 0.975. Mean cotinine levels decreased significantly by 74.7 ng/mL, p = 0.035. This is the first work demonstrating an association between smoking cessation and decreased solCD44 levels in oral rinses. Decreased expression of the tumorigenic CD44 may be one mechanism by which smoking cessation lowers cancer risk.

Increased Risk for Cerebral Hypoxia During Immediate Neonatal Transition After Birth in Term Neonates Delivered by Caesarean Section With Prenatal Tobacco Exposure

Introduction: Maternal tobacco smoking during pregnancy is a global health problem leading to an increased risk for fetal and neonatal morbidities. So far, there are no data of the potential impact of maternal smoking during pregnancy on the most vulnerable period after birth – the immediate postnatal transition. The aim of the present study was therefore, to compare cerebral oxygenation during immediate postnatal transition in term neonates with and without prenatal tobacco exposure.Methods: Included in this post-hoc analysis were healthy term neonates, with measurements of cerebral oxygenation (INVOS 5100C) during the first 15 min after birth, and for whom information on maternal smoking behavior during pregnancy was available. Neonates with prenatal tobacco exposure (smoking group) were matched 1:1 according to gestational age (±1 week), birth weight (±100 grams) and hematocrit (±5 %) to neonates without (non-smoking group). Cerebral regional tissue oxygen saturation (crSO2), cerebral fractional tissue oxygen extraction (cFTOE), arterial oxygen saturation (SpO2) and heart rate (HR) within the first 15 min after birth were compared between the two groups.Results: Twelve neonates in the smoking group with a median (IQR) gestational age of 39.1 (38.8–39.3) weeks and a birth weight of 3,155 (2,970–3,472) grams were compared to 12 neonates in the non-smoking group with 39.1 (38.7–39.2) weeks and 3,134 (2,963–3,465) grams. In the smoking group, crSO2 was significantly lower and cFTOE significantly higher until min 5 after birth. HR was significantly higher in the smoking group in min 3 after birth. Beyond this period, there were no significant differences between the two groups.Conclusion: Cerebral oxygenation within the first 5 min after birth was compromised in neonates with prenatal tobacco exposure. This observation suggests a higher risk for cerebral hypoxia immediately after birth due to fetal tobacco exposure.

Plasma Cotinine Is Positively Associated with Homocysteine in Smokers but Not in Users of Smokeless Tobacco

Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about the effect of snus on plasma homocysteine. Therefore, we studied, in a cross-section of subjects (n = 1375) from the Northern Sweden Health and Disease Study, with strictly defined current smokers (n = 194) and snus users (n = 47), the impact of tobacco exposure on tHcy, assessed by self-reported tobacco habits and plasma cotinine concentrations. The snus users had higher cotinine concentrations than the smokers. Cotinine, creatinine, methylmalonic acid, and the methylenetetrahydrofolate reductase genotype (MTHFR) T allele were positively associated with tHcy among the smokers, but not among the snus users. No association was observed between tHcy and the number of cigarettes/day. There was a positive association between cotinine and tHcy in the smokers, but not among the snus users. This indicates that substances other than nicotine in tobacco smoke could be responsible for the differential effects on homocysteine status. Self-reported smoking should be complemented by a cotinine assay whenever possible.

Perceptions, behaviours and attitudes towards smoking held by the male partners of Chinese pregnant women: a qualitative study

Background Direct associations of tobacco exposure during pregnancy with pregnancy complications and adverse birth outcomes have been proven. Previous studies suggest that expecting a child provides a valuable opportunity to promote behavioural changes, such as smoking cessation, among the male partners of pregnant women. Thorough understandings of Chinese expectant fathers’ smoking behaviour during the transition to fatherhood is a prerequisite to the development of appropriate interventions to facilitate smoking cessation. This study aimed to explore the perceptions, behaviours and attitudes related to smoking among male partners of pregnant women in China. Methods A descriptive phenomenological approach was adopted. A purposive sample of expectant fathers aged 18 years or older who had a tobacco use history within the past year were recruited at obstetrics and gynaecology clinics and invited to participate in one-to-one, 20–30-min semi-structured interviews. The data analysis followed Colaizzi’s descriptive phenomenological method. Results Twenty-five expectant fathers were interviewed. Four themes were generated: 1) the benefits of smoking and respondents’ misperceptions of the impact of smoking and SHS and neglectful attitude of the impact of smoking, which were given as the major reasons for continuing to smoke; 2) factors contributing to smoking cessation, including concern for the potential health impact of continued smoking on the pregnant partner and baby, the role of being father, and the encouragement to quit from family members; and 3) perceived barriers to smoking cessation, including withdrawal symptoms or cigarette cravings, absence of smoking cessation support, and increasing stress. Conclusion This study provides a comprehensive understanding of the perception, behaviours, and attitudes related to smoking among Chinese expectant fathers. The findings of this study can guide healthcare professionals and policymakers in combining the distribution of educational information about the hazards of SHS for maternal and neonatal health with smoking cessation assistance for expectant fathers through policy initiatives and other types of incentives and programmes targeted to enhance smoking cessation among this population. Trial registration Prospectively registered at clinicaltrial.org (NCT03401021) on 8 Jan 2018.