• Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study.

      Dossus, Laure; Franceschi, Silvia; Biessy, Carine; Navionis, Anne-Sophie; Travis, Ruth C; Weiderpass, Elisabete; Scalbert, Augustin; Romieu, Isabelle; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Bonnet, Fabrice; Fournier, Agnès; Fortner, Renee T; Kaaks, Rudolf; Aleksandrova, Krasimira; Trichopoulou, Antonia; La Vecchia, Carlo; Peppa, Eleni; Tumino, Rosario; Panico, Salvatore; Palli, Domenico; Agnoli, Claudia; Vineis, Paolo; Bueno-de-Mesquita, H B As; Peeters, Petra H; Skeie, Guri; Zamora-Ros, Raul; Chirlaque, María-Dolores; Ardanaz, Eva; Sánchez, Maria-Jose; Ramón Quirós, Jose; Dorronsoro, Miren; Sandström, Maria; Nilsson, Lena Maria; Schmidt, Julie A; Khaw, Kay-Tee; Tsilidis, Konstantinos K; Aune, Dagfinn; Riboli, Elio; Rinaldi, Sabina (2018-04-01)
      Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1 = 0.69, 95% CI: 0.49-0.98, Ptrend = 0.04) but not among men (ORT3vs.T1 = 1.36, 95% CI: 0.67-2.76, Ptrend = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1 = 1.59, 95% CI: 1.13-2.25, Ptrend = 0.01) but not in men (ORT3vs.T1 = 1.78, 95% CI: 0.80-3.98, Ptrend = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.
    • Adipose gene expression response of lean and obese mice to short-term dietary restriction.

      Schothorst, Evert M van; Keijer, Jaap; Pennings, Jeroen L A; Opperhuizen, Antoon; Brom, Charissa E van den; Kohl, Thomas; Franssen-van Hal, Nicole L W; Hoebee, Barbara (2006-06-01)
      Overweight and obesity lead to higher morbidity risks, which are alleviated even by mild weight loss. To gain insight in the molecular effects of weight loss in adipose tissue, we analyzed the effects of short-term dietary restriction (DR) on mice fed a low-fat diet (lean mice) or a high-fat diet (obese mice). Female C57Bl6/J mice on both diets were on DR until an average body weight loss of 20%, which was achieved in 8 to 12 days depending on body weight at the start of DR. Plasma free fatty acids and blood glucose levels decreased significantly on DR. In the (restricted) low-fat diet groups, gene expression analysis using adipose-enriched cDNA microarrays revealed only two transcripts to be significant differentially expressed by DR: up-regulation of malic enzyme (Mod1) and down-regulation of major urinary protein 1 (Mup1). Real-time polymerase chain reaction analysis confirmed these findings and showed, for the high-fat diet groups, an identical expression pattern for Mup1, whereas Mod1 showed an opposed gene expression pattern for the high-fat diet groups. In conclusion, initial weight loss induces transcriptional changes only in a very small number of adipose genes, which also depends on the (restricted) diet used.
    • ADMA, homocysteine and redox status improvement affected by 7-nitroindazole in spontaneously hypertensive rats

      Dovinová, Ima; Hrabárová, Eva; Jansen, Eugene; Kvandová, Miroslava; Majzúnová, Miroslava; Berenyiová, Andrea; Barančík, Miroslav (2018-10)
    • Adolescent meningococcal serogroup A, W and Y immune responses following immunization with quadrivalent meningococcal A, C, W and Y conjugate vaccine: Optimal age for vaccination.

      van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A M; Berbers, Guy A M (2017-08-24)
      Recently the incidence of meningococcal serogroup Y (MenY) and in particular serogroup W (MenW) invasive disease has risen in several European countries, including the Netherlands. Adolescents are a target group for primary prevention through vaccination to protect against disease and reduce carriage and induce herd protection in the population. The present study assessed MenA, MenW and MenY antibody levels in adolescents up to one year following primary vaccination with quadrivalent MenACWY-PS conjugated to tetanus toxoid (MenACWY-TT).
    • Advanced Toxicological Risk Assessment by Implementation of Ontologies Operationalized in Computational Models

      Staal, Yvonne C.M.; Pennings, Jeroen L.A.; Hessel, Ellen V.S.; Piersma, Aldert H.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. (2017-12)
    • Advancing food, nutrition, and health research in Europe by connecting and building research infrastructures in a DISH-RI: Results of the EuroDISH project

      Snoek, Harriëtte M.; Eijssen, Lars M.T.; Geurts, Marjolein; Vors, Cecile; Brown, Kerry A.; Bogaardt, Marc-Jeroen; Dhonukshe-Rutten, Rosalie A.M.; Evelo, Chris T.; Fezeu, Leopold K.; Finglas, Paul M.; Laville, Martine; Ocké, Marga; Perozzi, Giuditta; Poppe, Krijn; Slimani, Nadia; Tetens, Inge; Timotijevic, Lada; Zimmermann, Karin; van ’t Veer, Pieter (2018-03)
    • Adverse effects of levamisole in cocaine users: a review and risk assessment.

      Brunt, Tibor Markus; van den Berg, Jorrit; Pennings, Ed; Venhuis, Bastiaan (2017-06)
      The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.
    • An Adverse Outcome Pathway Analysis Employing DNA Methylation Effects in Arsenic-Exposed Zebrafish Embryos Supports a Role of Epigenetic Events in Arsenic-Induced Chronic Disease

      van der Ven, Leo T.M.; Jelinek, Jaroslav; Hodemaekers, Hennie M.; Zwart, Edwin P.; Ruiter, Sander; van den Brandhof, Evert-Jan; Issa, Jean-Pierre J.; Pennings, Jeroen L.A.; Luijten, Mirjam; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. (2017-12)
    • An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility of In Vitro and In Silico Methods in a Regulatory Context

      Sullivan, Kristie M.; Enoch, Steven J.; Ezendam, Janine; Sewald, Katherina; Roggen, Erwin L.; Cochrane, Stella; Physicians Committee for Responsible Medicine, Washington, District of Columbia.; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, England.; National Institute for Public Health and the Environment (RIVM), Centre for Health Protection, Bilthoven, The Netherlands.; Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany.; 3Rs Management & Consulting ApS (3RsMC ApS), Lyngby, Denmark.; Unilever SEAC, Sharnbrook, United Kingdom. (2017-09-07)
    • Age-Dependent Pre-Vaccination Immunity Affects the Immunogenicity of Varicella Zoster Vaccination in Middle-aged Adults

      van der Heiden, Marieke; de Rond, Lia G. H.; van Zelm, Menno C.; Berbers, Guy A. M.; Boots, Annemieke M. H.; Buisman, Anne-Marie (2018-01-23)
    • Age-specific Incidence and Prevalence of Keratoconus: A Nationwide Registration Study.

      Godefrooij, Daniel A; de Wit, G Ardine; Uiterwaal, Cuno S; Imhof, Saskia M; Wisse, Robert P L (2017-03)
      To determine the age-specific incidence and prevalence of keratoconus in the modern era of diagnostics.
    • Aggregate consumer exposure to isothiazolinones via household care and personal care products: Probabilistic modelling and benzisothiazolinone risk assessment.

      Garcia-Hidalgo, Elena; Schneider, Dovilé; von Goetz, Natalie; Delmaar, Christiaan; Siegrist, Michael; Hungerbühler, Konrad (2018-09)
      Consumers regularly use household care and personal care products (HC&PCPs). Isothiazolinones are included in HC&PCPs as preservatives and are being held responsible for an epidemic rise in allergic contact dermatitis (ACD). The objective of this study was to assess the origin and extent of dermal exposure in order to evaluate the risk of ACD from isothiazolinones in HC&PCP. Individual-based aggregate dermal exposure to four isothiazolinones was estimated using the newly proposed Probabilistic Aggregated Consumer Exposure Model-Kinetic, Dermal (PACEM-KD) by combining the reported individual use patterns for HC&PCP in Switzerland (N = 669 (558 adults), ages 0-91) with isothiazolinone concentrations measured in products used by the individual person. PACEM-KD extends the original PACEM by considering exposure duration, product dilution and skin permeability. PACEM-KD-based higher-tier exposure on palms (99th percentile) was 15.4 ng/cm2, 1.3 ng/cm2, 0.9 ng/cm2, and 0.08 ng/cm2 for the isothiazolinones 1,2‑Benzisothiazol‑3‑(2H)‑one (BIT), 2‑Octyl‑3(2H)‑isothiazolinone (OIT), 2‑Methylisothiazolin‑3(2H)‑one (MI), and 5‑Chloro‑2‑methyl‑4‑isothiazolin‑3‑one (CMI), respectively. Major sources of exposure to BIT included all-purpose cleaners, dishwashing detergent, and kitchen cleaner, while exposure to OIT mainly stems from a fungicide. For MI, the main contributors were dishwashing detergent and all-purpose wet wipes, and for CMI all-purpose cleaner. A Quantitative Risk Assessment (QRA) for BIT using Sensitization Assessment Factors (SAFs) indicates that around 1% of the Swiss population is at risk to be sensitized by BIT in cosmetics and household chemicals. For isothiazolinones in general the presented higher-tier modelling approach suggests that household cleaners are currently more important sources of exposure than cosmetics.
    • Aging-related trajectories of lung function in the general population-The Doetinchem Cohort Study.

      van Oostrom, Sandra H; Engelfriet, Peter M; Verschuren, W M Monique; Schipper, Maarten; Wouters, Inge M; Boezen, Marike; Smit, Henriëtte A; Kerstjens, Huib A M; Picavet, H Susan J (2018)
      The objective of this study was to explore trajectories of lung function decline with age in the general population, and to study the effect of sociodemographic and life style related risk factors, in particular smoking and BMI. For this purpose, we used data from the Doetinchem Cohort Study (DCS) of men and women, selected randomly from the general population and aged 20-59 years at inclusion in 1987-1991, and followed until the present. Participants in the DCS are assessed every five years. Spirometry has been performed as part of this assessment from 1994 onwards. Participants were included in this study if spirometric measurement of FEV1, which in this study was the main parameter of interest, was acceptable and reproducible on at least one measurement round, leading to the inclusion of 5727 individuals (3008 females). Statistical analysis revealed three typical trajectories. The majority of participants followed a trajectory that closely adhered to the Global Lung Initiative Reference values (94.9% of men and 96.4% of women). Two other trajectories showed a more pronounced decline. Smoking and the presence of respiratory complaints were the best predictors of a trajectory with stronger decline. A greater BMI over the follow-up period was associated with a more unfavorable FEV1 course both in men (β = -0.027 (SD = 0.002); P < 0.001) and in women (β = -0.008 (SD = 0.001); P < 0.001). Smokers at baseline who quit the habit during follow-up, showed smaller decline in FEV1 in comparison to persistent smokers, independent of BMI change (In men β = -0.074 (SD = 0.020); P < 0.001. In women β = -0.277 (SD = 0.068); P < 0.001). In conclusion, three typical trajectories of age-related FEV1 decline could be distinguished. Change in the lifestyle related risk factors, BMI and smoking, significantly impact aging-related decline of lung function. Identifying deviant trajectories may help in early recognition of those at risk of a diagnosis of lung disease later in life.
    • Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.

      Walsh, Naomi; Zhang, Han; Hyland, Paula L; Yang, Qi; Mocci, Evelina; Zhang, Mingfeng; Childs, Erica J; Collins, Irene; Wang, Zhaoming; Arslan, Alan A; Beane-Freeman, Laura; Bracci, Paige M; Brennan, Paul; Canzian, Federico; Duell, Eric J; Gallinger, Steven; Giles, Graham G; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hung, Rayjean J; Kooperberg, Charles; Kurtz, Robert C; Malats, Núria; LeMarchand, Loic; Neale, Rachel E; Olson, Sara H; Scelo, Ghislaine; Shu, Xiao O; Van Den Eeden, Stephen K; Visvanathan, Kala; White, Emily; Zheng, Wei; Albanes, Demetrius; Andreotti, Gabriella; Babic, Ana; Bamlet, William R; Berndt, Sonja I; Borgida, Ayelet; Boutron-Ruault, Marie-Christine; Brais, Lauren; Brennan, Paul; Bueno-de-Mesquita, Bas; Buring, Julie; Chaffee, Kari G; Chanock, Stephen; Cleary, Sean; Cotterchio, Michelle; Foretova, Lenka; Fuchs, Charles; M Gaziano, J Michael; Giovannucci, Edward; Goggins, Michael; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Janout, Vladimir; Klein, Eric A; Kurtz, Robert C; Laheru, Daniel; Lee, I-Min; Lu, Lingeng; Malats, Núria; Mannisto, Satu; Milne, Roger L; Oberg, Ann L; Orlow, Irene; Patel, Alpa V; Peters, Ulrike; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Sesso, Howard D; Severi, Gianluca; Silverman, Debra; Strobel, Oliver; Sund, Malin; Thornquist, Mark D; Tobias, Geoffrey S; Wactawski-Wende, Jean; Wareham, Nick; Weiderpass, Elisabete; Wentzensen, Nicolas; Wheeler, William; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Kraft, Peter; Li, Donghui; Jacobs, Eric J; Petersen, Gloria M; Wolpin, Brian M; Risch, Harvey A; Amundadottir, Laufey T; Yu, Kai; Klein, Alison P; Stolzenberg-Solomon, Rachael Z (2018-12-12)
      Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
    • Air pollution and airway resistance at age 8 years - the PIAMA birth cohort study.

      Finke, Isabelle; de Jongste, Johan C; Smit, Henriette A; Wijga, Alet H; Koppelman, Gerard H; Vonk, Judith; Brunekreef, Bert; Gehring, Ulrike (2018-07-17)
      Air pollution has been found to adversely affect children's lung function. Forced expiratory volume in 1 s and forced vital capacity from spirometry have been studied most frequently, but measurements of airway resistance may provide additional information. We assessed associations of long-term air pollution exposure with airway resistance.
    • Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE).

      Nagel, Gabriele; Stafoggia, Massimo; Pedersen, Marie; Andersen, Zorana J; Galassi, Claudia; Munkenast, Jule; Jaensch, Andrea; Sommar, Johan; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Krog, Norun H; Aamodt, Geir; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Fratiglioni, Laura; Sørensen, Mette; Tjønneland, Anne; Peeters, Petra H; Bueno-de-Mesquita, Bas; Vermeulen, Roel; Eeftens, Marloes; Plusquin, Michelle; Key, Timothy J; Concin, Hans; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Ranzi, Andrea; Cesaroni, Giulia; Forastiere, Francesco; Tamayo-Uria, Ibon; Amiano, Pilar; Dorronsoro, Miren; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole; Weinmayr, Gudrun (2018-04-26)
      Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancers of the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient air pollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-use regression models for particulate matter (PM) below 10 µm (PM10 ), below 2.5 µm (PM2.5 ), between 2.5 and 10 µm (PMcoarse ), PM2.5 absorbance and nitrogen oxides (NO2 and NOX ) as well as approximated by traffic indicators. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. During average follow-up of 14.1 years of 305 551 individuals, 744 incident cases of gastric cancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5 µg/m3 of PM2.5 was 1.38 (95%-CI 0.99;1.92) for gastric and 1.05 (95%-CI 0.62;1.77) for UADT cancers. No associations were found for any of the other exposures considered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influence markedly the effect estimate for PM2.5 and gastric cancer. Higher estimated risks of gastric cancer associated with PM2.5 was found in men (HR 1.98 (1.30;3.01)) as compared to women (HR 0.85 (0.5;1.45)). This large multicentre cohort study shows an association between long-term exposure to PM2.5 and gastric cancer, but not UADT cancers, suggesting that air pollution may contribute to gastric cancer risk. This article is protected by copyright. All rights reserved.
    • Air pollution exposure and lung function until age 16 years: the PIAMA birth cohort study.

      Milanzi, Edith B; Koppelman, Gerard H; Smit, Henriette A; Wijga, Alet H; Oldenwening, Marieke; Vonk, Judith M; Brunekreef, Bert; Gehring, Ulrike (2018-09)
      Evidence for the effects of air pollution exposure on lung function growth into adolescence is scarce. We investigated associations of air pollution exposure with lung function and lung function growth until age 16.We conducted both longitudinal (n=915) and cross-sectional (n=721) analyses of associations of air pollution exposure with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) growth from ages eight to 16 and FEV1 and FVC at age 16. We estimated residential concentrations of nitrogen dioxide (NO2), "soot" and particulate matter (PMx, where x is the 50% cut-off aerodynamic diameter in µm) with diameters of <2.5 µm (PM2.5), <10 µm (PM10) and 2.5-10 µm (PMcoarse) during the preschool, primary school and secondary school time windows by land use regression models. Associations with (growth in) FEV1 and FVC were analysed by linear (mixed effects) regression.Higher air pollution exposure was associated with reduced FEV1 growth (e.g. adjusted difference -0.26% (95% CI -0.49 to -0.03%) per interquartile range increase in secondary school PM2.5) and lower FEV1 (adjusted difference -2.36% (95% CI -3.76 to -0.94%)), but was not adversely associated with FVC. Associations with FEV1 were stronger in boys than girls and were not modified by asthma status.Higher air pollution exposure may lead to increased airway obstruction, but not reduced lung volume in adolescence.
    • Air Pollution from Livestock Farms Is Associated with Airway Obstruction in Neighboring Residents.

      Borlée, Floor; Yzermans, C Joris; Aalders, Bernadette; Rooijackers, Jos; Krop, Esmeralda; Maassen, Catharina B M; Schellevis, François; Brunekreef, Bert; Heederik, Dick; Smit, Lidwien A M (2017-11-01)
      Livestock farm emissions may not only affect respiratory health of farmers but also of neighboring residents.
    • Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans.

      Behndig, A F; Mudway, I S; Brown, J L; Stenfors, N; Helleday, R; Duggan, S T; Wilson, S J; Boman, C; Cassee, Flemming R; Frew, A J; Kelly, F J; Sandström, T; Blomberg, A (2006-02-01)
      Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a hierarchical fashion with protective antioxidant responses predominating at low doses and inflammation and injury only occurring at higher concentrations. In the present study, the authors examined whether similar responses occurred in vivo, specifically whether antioxidants were upregulated following a low-dose DE challenge and investigated how these responses related to the development of airway inflammation at different levels of the respiratory tract where particle dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was performed with lavage and mucosal biopsies taken to assess airway redox and inflammatory status. Following DE exposure, the current authors observed an increase in bronchial mucosa neutrophil and mast cell numbers, as well as increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in bronchial lavage. No inflammatory responses were seen in the alveolar compartment, but both reduced glutathione and urate concentrations were increased following diesel exposure. In conclusion, the lung inflammatory response to diesel exhaust is compartmentalised, related to differing antioxidant responses in the conducting airway and alveolar regions.
    • Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort.

      Botteri, E; Ferrari, P; Roswall, N; Tjønneland, A; Hjartåker, A; Huerta, J M; Fortner, R T; Trichopoulou, A; Karakatsani, A; La Vecchia, C; Pala, V; Perez-Cornago, A; Sonestedt, E; Liedberg, F; Overvad, K; Sánchez, M J; Gram, I T; Stepien, M; Trijsburg, L; Börje, L; Johansson, M; Kühn, T; Panico, S; Tumino, R; Bueno-de-Mesquita, H B As; Weiderpass, E (2017-11-15)
      Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00-1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01-1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03-2.40) compared to those reporting moderate intakes (<6 g/day), but no dose-response relationship emerged. In men, an increased risk of aggressive forms of UCC was observed even at lower doses (>6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits > 24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01-1.91) and smokers (1.39; 95% CI 1.01-1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking.