Systematic review of the evidence relating FEV1 decline to giving up smoking

<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV₁) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV₁decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p

Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence

Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24+ population with a proliferative advantage and stem-like transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations. Together, these observations provide unprecedented high-resolution molecular portraits of mutant-IDH1-dependent epigenomic reprogramming. These findings have substantial implications for understanding of mutant IDH function and for optimizing therapeutic approaches to targeting IDH-mutant tumors

The association of neighbourhood and individual social capital with consistent self-rated health: a longitudinal study in Brazilian pregnant and postpartum women.

BACKGROUND: Social conditions, social relationships and neighbourhood environment, the components of social capital, are important determinants of health. The objective of this study was to investigate the association of neighbourhood and individual social capital with consistent self-rated health in women between the first trimester of pregnancy and six months postpartum. METHODS: A multilevel cohort study in 34 neighbourhoods was performed on 685 Brazilian women recruited at antenatal units in two cities in the State of Rio de Janeiro, Brazil. Self-rated health (SRH) was assessed in the 1st trimester of pregnancy (baseline) and six months after childbirth (follow-up). The participants were divided into two groups: 1. Good SRH--good SRH at baseline and follow-up, and, 2. Poor SRH--poor SRH at baseline and follow-up. Exploratory variables collected at baseline included neighbourhood social capital (neighbourhood-level variable), individual social capital (social support and social networks), demographic and socioeconomic characteristics, health-related behaviours and self-reported diseases. A hierarchical binomial multilevel analysis was performed to test the association between neighbourhood and individual social capital and SRH, adjusted for covariates. RESULTS: The Good SRH group reported higher scores of social support and social networks than the Poor SRH group. Although low neighbourhood social capital was associated with poor SRH in crude analysis, the association was not significant when individual socio-demographic variables were included in the model. In the final model, women reporting poor SRH both at baseline and follow-up had lower levels of social support (positive social interaction) [OR 0.82 (95% CI: 0.73-0.90)] and a lower likelihood of friendship social networks [OR 0.61 (95% CI: 0.37-0.99)] than the Good SRH group. The characteristics that remained associated with poor SRH were low level of schooling, Black and Brown ethnicity, more children, urinary infection and water plumbing outside the house. CONCLUSIONS: Low individual social capital during pregnancy, considered here as social support and social network, was independently associated with poor SRH in women whereas neighbourhood social capital did not affect women's SRH during pregnancy and the months thereafter. From pregnancy and up to six months postpartum, the effect of individual social capital explained better the consistency of SRH over time than neighbourhood social capital