Association study of genes associated to asthma in a specific environment, in an asthma familial collection located in a rural area influenced by different industries

Eight candidate genes selected in this study were previously associated with gene-environment interactions in asthma in an urban area. These genes were analyzed in a familial collection from a founder and remote population (Saguenay–Lac-Saint-Jean; SLSJ) located in an area with low air levels of ozone but with localized areas of relatively high air pollutant levels, such as sulphur dioxide, when compared to many urban areas. Polymorphisms (SNPs) were extracted from the genome-wide association study (GWAS) performed on the SLSJ familial collection. A transmission disequilibrium test (TDT) was performed using the entire family sample (1,428 individuals in 254 nuclear families). Stratification according to the proximity of aluminium, pulp and paper industries was also analyzed. Two genes were associated with asthma in the entire sample before correction (CAT and NQO1) and one was associated after correction for multiple analyses (CAT). Two genes were associated when subjects were stratified according to the proximity of aluminium industries (CAT and NQO1) and one according to the proximity of pulp and paper industries (GSTP1). However, none of them resisted correction for multiple analyses. Given that the spatial pattern of environmental exposures can be complex and inadequately represented by a few stationary monitors and that exposures can also come from sources other than the standard outdoor air pollution (e.g., indoor air, occupation, residential wood smoke), a new approach and new tools are required to measure specific and individual pollutant exposures in order to estimate the real impact of gene-environment interactions on respiratory health

Reanalysis-driven climate simulation over CORDEX North America domain using the Canadian Regional Climate Model, version 5: model performance evaluation

The performance of reanalysis-driven Canadian Regional Climate Model, version 5 (CRCM5) in reproducing the present climate over the North American COordinated Regional climate Downscaling EXperiment domain for the 1989–2008 period has been assessed in comparison with several observation-based datasets. The model reproduces satisfactorily the near-surface temperature and precipitation characteristics over most part of North America. Coastal and mountainous zones remain problematic: a cold bias (2–6 °C) prevails over Rocky Mountains in summertime and all year-round over Mexico; winter precipitation in mountainous coastal regions is overestimated. The precipitation patterns related to the North American Monsoon are well reproduced, except on its northern limit. The spatial and temporal structure of the Great Plains Low-Level Jet is well reproduced by the model; however, the night-time precipitation maximum in the jet area is underestimated. The performance of CRCM5 was assessed against earlier CRCM versions and other RCMs. CRCM5 is shown to have been substantially improved compared to CRCM3 and CRCM4 in terms of seasonal mean statistics, and to be comparable to other modern RCMs

A global numerical study of radon-222 and lead-210 in the atmosphere using the AES and York University CDT General Circulation Model (AYCG)

The Canadian Climate Center (CCC) GCM has been modified to allow its use for studies in atmospheric chemistry. The initial experiments reported here have been run to test and allow sensitivity studies of the new transport module. The impact of different types of parameterization for the convective mixing have been studied based on the large scale evolution of Rn-222 and Pb-210. Preliminary results have shown that the use of a scheme, which mixes unstable columns over a very short time scale, produces a global distribution of lead that agrees in some aspects with observations. The local impact of different mixing schemes on a short lived tracer like the radon is very important

Analysis of streamflow characteristics over Northeastern Canada in a changing climate

An analysis of streamflow characteristics (i.e. mean annual and seasonal flows and extreme high and low flows) in current and future climates for 21 watersheds of north-east Canada covering mainly the province of Quebec is presented in this article. For the analysis, streamflows are derived from a 10-member ensemble of Canadian Regional Climate Model (CRCM) simulations, driven by the Canadian Global Climate Model simulations, of which five correspond to current 1970–1999 period, while the other five correspond to future 2041–2070 period. For developing projected changes of streamflow characteristics from current to future periods, two different approaches are used: one based on the concept of ensemble averaging while the other approach is based on merged samples of current and similarly future simulations following multiple comparison tests. Verification of the CRCM simulated streamflow characteristics for the 1970–1999 period suggests that the model simulated mean hydrographs and high flow characteristics compare well with those observed, while the model tends to underestimate low flow extremes. Results of projected changes to mean annual streamflow suggest statistically significant increases nearly all over the study domain, while those for seasonal streamflow show increases/decreases depending on the season. Two- and 5-year return levels of 15-day low flows are projected to increase significantly over most part of the study domain, though the changes are small in absolute terms. Based on the ensemble averaging approach, changes to 10- and 30-year return levels of high flows are not generally found significant. However, when a similar analysis is performed using longer samples, significant increases to high flow return levels are found mainly for northernmost watersheds. This study highlights the need for longer samples, particularly for extreme events in the development of robust projections

Polar mesoscale cyclones in the northeast Atlantic: Comparing climatologies from ERA-40 and satellite imagery

Polar mesoscale cyclones over the subarctic are thought to be an important component of the coupled atmosphere–ocean climate system. However, the relatively small scale of these features presents some concern as to their representation in the meteorological reanalysis datasets that are commonly used to drive ocean models. Here polar mesocyclones are detected in the 40-Year European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis dataset (ERA-40) in mean sea level pressure and 500-hPa geopotential height, using an automated cyclone detection algorithm. The results are compared to polar mesocyclones detected in satellite imagery over the northeast Atlantic, for the period October 1993–September 1995. Similar trends in monthly cyclone numbers and a similar spatial distribution are found. However, there is a bias in the size of cyclones detected in the reanalysis. Up to 80% of cyclones larger than 500 km are detected in MSL pressure, but this hit rate decreases, approximately linearly, to ∼40% for 250-km-scale cyclones and to ∼20% for 100-km-scale cyclones. Consequently a substantial component of the associated air–sea fluxes may be missing from the reanalysis, presenting a serious shortcoming when using such reanalysis data for ocean modeling simulations. Eight maxima in cyclone density are apparent in the mean sea level pressure, clustered around synoptic observing stations in the northeast Atlantic. They are likely spurious, and a result of unidentified shortcomings in the ERA-40 data assimilation procedure

Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics

Background: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis. Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic airways. Objective: This study aimed to determine if (1) collagen deposition in asthmatic airways is associated with ATG5 expression and (2) ATG5 protein expression is associated with asthma per se and severity. Methods: Gene expression of transforming growth factor beta 1, various asthma-related collagen types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III, alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and ATG5 were measured using mRNA isolated from bronchial biopsies of refractory asthmatic subjects and assessed for pairwise associations. Protein expression of ATG5 in the airways was measured and associations were assessed for asthma per se, severity, and lung function. Main results: In refractory asthmatic individuals, gene expression of ATG5 was positively associated with COL5A1 in the airways. No association was detected between ATG5 protein expression and asthma per se, severity, and lung function. Conclusion and clinical relevance: Positive correlation between the gene expression patterns of ATG5 and COL5A1 suggests that dysregulated autophagy may contribute to subepithelial fibrosis in the airways of refractory asthmatic individuals. This finding highlights the therapeutic potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat refractory asthmatic individuals

Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

BACKGROUND: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. OBJECTIVE: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. METHODS: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed. RESULTS: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P<5x10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7 ), 14q22 (rs7493885 near NIN; P=2.9x10-6 ) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. CONCLUSION AND CLINICAL RELEVANCE: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms. This article is protected by copyright. All rights reserved

Symposium on Obesity and Asthma-November 2006

L’asthme et l’obésité sont fréquemment associés et l’obésité est considérée comme un facteur impliqué tant dans l’augmentation de la sévérité que dans le développement de l’asthme. Ce document est un compte-rendu des présentations effectuées dans le cadre d’un symposium du Réseau en santé respiratoire du Fonds de la recherche en santé du Québec qui a eu lieu à Montréal le 2 novembre 2006, en collaboration avec le McGill University – Strauss Severe Asthma Program, l’Université Laval (Québec) et l’Université de Montréal. Au cours de cette rencontre, divers aspects de la relation entre obésité et asthme ont été abordés, en regard des modèles animaux, des influences génétiques, hormonales et physiologiques, de l’influence des comorbidités (ex : syndrome d’apnée du sommeil), de l’épidémiologie, des aspects cliniques et psychologiques et, enfin, du traitement de l’asthme chez la personne obèse.Asthma and obesity are frequently associated, and obesity has been considered a factor contributing to both an increase in severity of asthma and to its development. The present document summarizes the proceedings of a symposium held in Montreal, Quebec, on November 2, 2006, under the auspices of the Réseau en santé respiratoire du Fonds de la recherche en santé du Québec in collaboration with the McGill University - Strauss Severe Asthma Program, Université Laval (Quebec City) and Université de Montréal. It includes an overview of the various aspects of the relationships between asthma and obesity with regard to animal models; genetic, hormonal and physiological determinants; influence of comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and psychological features; and management of asthma in the obese population