Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function. METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

The locus C11orf30 increases susceptibility to poly-sensitization.

A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.

LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk.

BACKGROUND: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. METHODS: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. RESULTS: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). CONCLUSIONS: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.

Exposure of thermoelectric power-plant workers to volatile organic compounds from fuel oil: genotoxic and cytotoxic effects in buccal epithelial cells.

Thermoelectric power-plant workers are constantly exposed to high levels of potentially genotoxic gaseous substances, such as volatile organic compounds (VOCs) from the combustion of fuel oil or the processing of naphtha. The aim of the present study was to estimate the association between such occupational exposure and the frequency of micronucleated cells and cells with other nuclear anomalies. Buccal epithelial cells were collected from a total of 44 power-plant workers (exposed group) and 47 administrative workers (non-exposed group), and examined for the frequency of micronucleated cells (MNC) and of cells with other nuclear anomalies (ONA: pyknosis, karyolysis, and karyorrhexis) by means of the micronucleus assay. The frequencies of MNC and ONA per 1000 cells in the exposed group (1.8‰ and 82.4‰, respectively) were significantly higher than in the non-exposed group (0.2‰ and 58.3‰, respectively). The exposed group had a twelve-fold increase in risk for formation of MNC compared with non-exposed individuals (RR=12.1; 95% CI, 5.0-29.2; P<0.001). The confounding factors analyzed (age, smoking status, alcohol consumption, and mouthwash use) did not show any significant association with the frequency of MNC or ONA. The findings of this study show that workers from power plants exposed to VOCs have a significantly elevated risk for DNA damage. Therefore, bio-monitoring of DNA damage is recommended for this group of workers.