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Abstract
Chronic exposure to fine particles (PM2.5-0.3) can have dramatic consequences for health, especially for the most vulnerable people, such as asthmatics. In order to better understand the impact of PM2.5-0.3 from different emission sources on the modulation of gene expression, a 3-D in vitro model of human bronchial epithelium (MucilAir-HF™) reconstructed from primary cells from healthy (EpiH) or asthmatic (EpiA) donors was used. Repeated exposures to PM2.5-0.3 (collected at industrial or road traffic sites) were performed during three weeks, and epithelia were sacrificed to extract RNAs and assess gene expression. Data were analysed according to emission sources, physiological status and exposure doses using an innovative method consisting of a graph analysis on pairwise expression ratios. Results obtained were related to those obtained with the common ΔΔCt method. Graph analysis on pairwise expression ratios proved to have better statistical properties than the common ΔΔCt method and demonstrated that repeated PM2.5-0.3 exposures induced a dose-dependent up-regulation of metabolic genes (CYPs) and a down-regulation of inflammation gene (CXCL10). These modulations were greater for "industrial" than for "urban traffic" PM2.5-0.3, and the effects were found to be greater after exposure of EpiA compared to EpiH, emphasing the importance of the epithelium physiological status in the sensitivity to particles. In conclusion, our study, original in terms of experimental conditions and statistical analysis method, highlights the importance of particle chemistry on the modulation of cellular and molecular responses, which may vary according to the vulnerability of the individuals.

Background: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms. Methods: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined. Results: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV1 for an inter-quartile range of 1160 ng/m3 exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase]. Conclusion: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure. ; The study in Sabadell was funded by grants from Instituto de Salud Carlos III Red INMA (G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 19995GR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació la Marató de TV3 (090430), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), EU Commission (261357, 308333 and 603794), the European Community's Seventh Framework Programme (FP7/2007/2013) under grant agreements 308333-HELIX Project and 308610-EXPOSOMICS Project. Dr Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128). The study in Valencia was funded by grants from European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (FIS-FEDER funds: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/02032, PI14/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), and Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249).

BACKGROUND: Asthma, rhinitis and eczema often co-occur in children, but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis and eczema using unsupervised statistical techniques. METHODS: We included 17 209 children at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age of onset and treatments of asthma, rhinitis and eczema; immunoglobulin E sensitization; weight; and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organizing maps. RESULTS: Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70% and 79% of children, respectively) was characterized by a low prevalence of symptoms and sensitization, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitization. Ninety-nine percentage of children with comorbidities (co-occurrence of asthma, rhinitis and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses.CONCLUSION:At 4 and 8 years, at the population level, asthma, rhinitis and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases. ; This work was supported by Mechanisms of the Develop-ment of ALLergy (MeDALL), a collaborative project con-ducted within the European Union under the HealthCooperation Work Programme of the 7th Framework pro-gramme (grant agreement No. 261357)