Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus

Background & Aims: Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia. Methods: We analyzed data from patients with BE identified from the population-based Northern Ireland BE register, diagnosed between 1993 and 2005 with specialized intestinal metaplasia (n = 3167). Data on clinical, demographic, and lifestyle factors related to diagnosis of BE were collected from hospital case notes. We used the Northern Ireland Cancer Registry to identify which of these patients later developed esophageal adenocarcinoma, adenocarcinomas of the gastric cardia, or esophageal high-grade dysplasia. Cox proportional hazards models were used to associate lifestyle factors with risk of progression.
Results: By December 31, 2008, 117 of the patients with BE developed esophageal high-grade dysplasia or adenocarcinomas of the esophagus or gastric cardia. Current tobacco smoking was significantly associated with an increased risk of progression (hazard ratio = 2.03; 95% confidence interval, 1.29-3.17) compared with never smoking, and across all strata of smoking intensity. Alcohol consumption was not related to risk of progression. Measures of body size were infrequently reported in endoscopy reports, and body size was not associated with risk of progression.
Conclusions: Smoking tobacco increases the risk of progression to cancer or high-grade dysplasia 2-fold among patients with BE, compared with patients with BE that have never smoked. Smoking cessation strategies should be considered for patients with BE.

Job Strain and Tobacco Smoking:An Individual-Participant Data Meta-Analysis of 166 130 Adults in 15 European Studies

BACKGROUND: Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults. METHODOLOGY AND PRINCIPAL FINDINGS: We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking. CONCLUSIONS: Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

AßPP over-expressing transgenic rat model of Alzheimer's disease utilizing the Tg2576 mouse protocol.

The current study examined behavioral and histological effects of amyloid-ß (Aß) protein precursor (AßPP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg+ rats were bred with female wild-type rats to generate litters of hemizygous Tg+ and Tg- offspring. Tg+ rats and Tg- littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure. There were no significant behavioral differences between Tg+ rats and Tg- littermates at 4 months old but there were significant differences at 8 and 12 months old, and in probe trials at 8 and 12 months old, the Tg+ rats spent significantly less time and covered less distance in the platform zone. Under acquisition of a fixed-consecutive number schedule at 3 months old, Tg- littermates demonstrated a longer latency to learning the response rule than Tg+ rats; while this might seem paradoxical, it is consistent with the role of overexpression of AßPP in learning. Histological analyses revealed activated astrocytes in brains of Tg+ rats but not Tg- littermates at 6 months old, and thioflavin-S positive staining in the hippocampus and cortex of 17-month old Tg+ rats but not Tg- littermates. Quantification of Aß load in the brain at 22 months indicated high levels of Aß38, Aß40, and Aß42 in the Tg+ rats. These data suggest this model might provide a valuable resource for AD research.

Proximity to a tobacco store and smoking cessation:A cohort study

Background
It is not clear whether the availability of tobacco affects the likelihood of smoking cessation. We examined whether the proximity to a tobacco store and
the number of stores were associated with smoking cessation, and compared results for proximity variables based on walking and straight-line (as the crow flies) distance.

Methods
The study population consisted of 8751 baseline smokers from the Finnish Public Sector study in 1997–2005. Smoking intensity (cigarettes/day) was
determined at baseline and smoking cessation was determined from a follow-up survey in 2008–2009. Proximity was measured using straight-line and walking
distance from home to the nearest tobacco store, and another exposure variable was the number of stores within 0.50 km from home. We calculated associations
with log-binomial regression models, adjusting for individual-level and area-level confounders.

Results
Of the participants, 3482 (39.8%) quit smoking during the follow-up (mean follow-up 5.5 years, SD 2.3 years). Among men who were moderate/heavy smokers at baseline and lived <0.50 km walking distance from the nearest tobacco store, the likelihood of smoking cessation was 27% (95% CI 12% to 40%) lower compared with those living ≥0.50 km from a store. Having even one store within 0.50 km walking distance from home decreased cessation in men who were moderate/heavy smokers by 37% (95% CI 19% to 51%). No decrease was found for men who were light smokers at baseline or for women.

Conclusions
Living within walking distance of a tobacco store reduced the likelihood of smoking cessation among men who were moderate/heavy smokers.

Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity

Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

Consistency of arsenic speciation in global tobacco products with implications for health and regulation

Background: Tobacco smoke is a major risk to the health of its users and arsenic is among the components of smoke present at concentrations of toxicological concern. There are significant variations in human toxicity between inorganic and organic arsenic species and the aim of this study was to determine whether there are predictable relationships among major arsenic species in tobacco that could be useful for risk assessment.

Methods: 14 samples of tobacco were studied spanning a wide range of concentrations in samples from different geographical regions, including certified reference materials and cigarette products. Inorganic and major organic arsenic species were extracted from powdered tobacco samples by nitric acid using microwave digestion. Concentrations of arsenic species in these extracts were determined using HPLC-ICPMS.

Results: The concentrations of total inorganic arsenic species range from 144 to 3914 mu g kg(-1), while organic species dimethylarsinic acid (DMA) ranges from 21 to 176 mu g As kg(-1), and monomethylarsonic acid (MA) ranges from 30 to 116 mu g kg(-1). The percentage of species eluted compared to the total arsenic extracted ranges from 11.1 to 36.8% suggesting that some As species (possibly macro-molecules, strongly complexed or in organic forms) do not elute from the column. This low percentage of column-speciated arsenic is indicative that more complex forms of arsenic exist in the tobacco. All the analysed species correlate positively with total arsenic concentration over the whole compositional range and regression analysis indicates a consistent ratio of about 4:1 in favour of inorganic arsenic compared with MA + DMA.

Conclusions: The dominance of inorganic arsenic species among those components analysed is a marked feature of the diverse range of tobaccos selected for study. Such consistency is important in the context of a WHO expert panel recommendation to regulate tobacco crops and products using total arsenic concentration. If implemented more research would be required to develop models that accurately predict the smoker's exposure to reduced inorganic arsenic species on the basis of leaf or product concentration and product design features.