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1. A genome-wide association meta-analysis identifies new childhood obesity loci

Author

Bradfield, Jonathan P, Taal, H Rob, Timpson, Nicholas J, Scherag, Andre, Lecoeur, Cecile, Warrington, Nicole M, Hypponen, Elina, Holst, Claus, Valcarcel, Beatriz, Thiering, Elisabeth, Salem, Rany M, Schumacher, Fredrick R, Cousminer, Diana L, Sleiman, Patrick MA, Zhao, Jianhua, Berkowitz, Robert I, Vimaleswaran, Karani S, Jarick, Ivonne, Pennell, Craig E, Evans, David M, St Pourcain, Beate, Berry, Diane J, Mook-Kanamori, Dennis O, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, van Duijn, Cornelia M, van der Valk, Ralf JP, de Jongste, Johan C, Postma, Dirkje S, Boomsma, Dorret I, Gauderman, W James, Hassanein, Mohamed T, Lindgren, Cecilia M, Magi, Reedik, Boreham, Colin AG, Neville, Charlotte E, Moreno, Luis A, Elliott, Paul, Pouta, Anneli, Hartikainen, Anna-Liisa, Li, Mingyao, Raitakari, Olli, Lehtimaki, Terho, Eriksson, Johan G, Palotie, Aarno, Dallongeville, Jean, Das, Shikta, Deloukas, Panos, McMahon, George, Ring, Susan M, Kemp, John P, Buxton, Jessica L, Blakemore, Alexandra IF, Bustamante, Mariona, Guxens, Monica, Hirschhorn, Joel N, Gillman, Matthew W, Kreiner-Moller, Eskil, Bisgaard, Hans, Gilliland, Frank D, Heinrich, Joachim, Wheeler, Eleanor, Barroso, Ines, O'Rahilly, Stephen, Meirhaeghe, Aline, Sorensen, Thorkild IA, Power, Chris, Palmer, Lyle J, Hinney, Anke, Widen, Elisabeth, Farooqi, I Sadaf, McCarthy, Mark I, Froguel, Philippe, Meyre, David, Hebebrand, Johannes, Jarvelin, Marjo-Riitta, Jaddoe, Vincent WV, Smith, George Davey, Hakonarson, Hakon, and Grant, Struan FA

Subjects
Biological Sciences, Genetics, Pediatric, Nutrition, Obesity, Human Genome, Metabolic and endocrine, Oral and gastrointestinal, Stroke, Cancer, Cardiovascular, Adolescent, Adult, Body Mass Index, Case-Control Studies, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Young Adult, Early Growth Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (

Published
2012

4. Efficacy of a loading dose of IV salbutamol in children with severe acute asthma admitted to a PICU: a randomized controlled trial

Author

Boeschoten, Shelley A., Buysse, Corinne M.P., de Winter, Brenda C.M., van Rosmalen, Joost, de Jongste, Johan C., de Jonge, Rogier C., Heisterkamp, Sabien G.J., van Woensel, Job B., Kneyber, Martin C.J., van Zwol, Annelies, Boehmer, Annemie L.M., de Hoog, Matthijs, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Pediatric Surgery, Pharmacy, Epidemiology, and Pediatrics

Subjects
IV salbutamol bolus, Intensive care, Severe acute asthma, Therapy, Status asthmaticus, NEBULIZED IPRATROPIUM, Children, INTRAVENOUS SALBUTAMOL, EARLY MANAGEMENT
Abstract

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children’s hospitals included children (2–18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10–13) in the intervention group and 11 (9–12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5–24) in the intervention group and 4 μg/L (IQR 0–7) in the control group (p = 0.001). Side effects were comparable between both groups. Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered.What is Known:• Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids.• During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction.What is New:• This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU.• This study found no clinically significant side effects from the loading dose.

Published
2022

5. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma

Author

van Meel, Evelien R, Mensink-Bout, Sara M, den Dekker, Herman T, Ahluwalia, Tarunveer S, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baïz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bønnelykke, Klaus, Carlsson, Christian J, Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchen, Karel, Eggesbø, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J, Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M, Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E, Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Mélen, Erik, Mehegan, John, Mommers, Monique, Nybo Andersen, Anne-Marie, Nystad, Wenche, Pedersen, Eva S L, Pekkanen, Juha, Peltola, Ville, Pike, Katharine C, Pinot de Moira, Angela, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S, Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C, Jaddoe, Vincent W V, Duijts, Liesbeth, IRAS OH Epidemiology Chemical Agents, Salvy-Córdoba, Nathalie, The Generation R Study Group, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Herlev and Gentofte Hospital, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St Mary's Hospital [London], University Hospital Southampton NHS Foundation Trust, Departamento de Ciências da Saúde Pública e Forenses e Educação Médica [Porto, Portugal], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto-Universidade do Porto = University of Porto, ISPUP-EPIUnit, University of Porto Medical School and Institute of Public Health, Marien-Hospital Wesel gGmbH, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), University of Southern California (USC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Barts & The London School of Medicine and Dentistry, Linköping university hospital, Norwegian Institute of Public Health [Oslo] (NIPH), Alma Mater Studiorum University of Bologna (UNIBO), Helmholtz Zentrum München = German Research Center for Environmental Health, University Children’s Hospital Basel = Hôpital pédiatrique universitaire des deux Bâle [Bâle, Suisse] (UKBB), Lazio Regional Health Service [Rome], Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Swansea University Medical School [Swansea, Royaume-Uni], Swansea University, University of Southampton, Nofer Institute of Occupational Medicine (NIOM), Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Würzburg = Universität Würzburg, Bavarian Health and Food Safety Authority, School of Public Health, Physiotherapy and Sports Science [Dublin, Irlande], University College Dublin [Dublin] (UCD), National School of Public Health [Athens], IMIM-Hospital del Mar, Generalitat de Catalunya, Flemish Institute for Technological Research (VITO), Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern] (UNIBE), Bern University Hospital [Berne] (Inselspital), Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Sach's Children's Hospital [Stockholm], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Copenhagen = Københavns Universitet (UCPH), TKK Helsinki University of Technology (TKK), Turku University Hospital (TYKS), Bristol Royal Hospital for Children, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK, University of Crete [Heraklion] (UOC), Epidemiologie, RS: CAPHRI - R5 - Optimising Patient Care, Pediatrics, Epidemiology, IRAS OH Epidemiology Chemical Agents, and Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Vital Capacity, Infant, 610 Medicine & health, ALSPAC, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Asthma, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 360 Social problems & social services, Child, Preschool, Forced Expiratory Volume, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Humans, Prospective Studies, Child, Preschool, Lung, Respiratory Tract Infections
Abstract

Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections. A comprehensive list of grant funding is available on the ALSPAC website (www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). BAMSE: BAMSE was funded by the Swedish Research Council, the Swedish Heart Lung Foundation, ALF Region Stockholm and SFO Epidemiology Karolinska Institutet. E. Mélen is supported by a European Research Council grant (TRIBAL, 757919). BiB (Born in Bradford): BiB is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, practitioners and researchers who have made BiB happen. The BiB study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). Core support for BiB is also provided by the Wellcome Trust (WT101597MA). BILD: This study was funded by the Swiss National Science Foundation (320030_163311). CoNER: Funds were obtained from the special programme (Programmi speciali – Art.12 bis, comma 6 D.lgs.229/99 Sanitaria e della Vigilanza sugli Enti) funded by the Italian Ministry of Health. Approval for the study was obtained from the Ethics Committee of the S. Orsola-Malpighi Teaching Hospital in April 2004 (52/2004/U/Tess). COPSAC 2000 and COPSAC 2010: All funding received by COPSAC is listed on www.copsac.com. The Lundbeck Foundation (R16-A1694), Ministry of Health (903516), Danish Council for Strategic Research (0603-00280B) and Capital Region Research Foundation have provided core support to the COPSAC research centre. We express our deepest gratitude to the children and families of the COPSAC 2000 and COPSAC 2010 cohort studies for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. DNBC (Danish National Birth Cohort): The authors would like to thank the participants, the first Principal Investigator of DNBC, Jørn Olsen, the scientific managerial team and DNBC secretariat for being, establishing, developing and consolidating the DNBC. The DNBC was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, Pharmacy Foundation, Egmont Foundation, March of Dimes Birth Defects Foundation, Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and Lundbeck Foundation. Follow-up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), Lundbeck Foundation (195/04, R100-A9193), Innovation Fund Denmark 0603-00294B (09-067124), Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012) and Danish Council for Independent Research (DFF-4183-00594, DFF-4183-00152). A. Pinot de Moira is funded by a Lundbeck Foundation grant (R264-2017-3099). EDEN: We thank the EDEN mother–child cohort study group (I. Annesi-Maesano, J.Y. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G. Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer and O. Thiebaugeorges). We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 programme), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, MeDALL projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale complementary health insurance (MGEN), French national agency for food security, and French speaking association for the study of diabetes and metabolism (ALFEDIAM). The funding source had no involvement in the conception of the present study. FLEHS: This study was conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Dept of the Environment of the Flemish Government, Flemish Agency of Care and Health, and Flemish Dept of Economy, Science and Innovation. GASPII: The GASPII cohort was funded by the Italian Ministry of Health (2001), the research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement 261357 (MeDALL). Generation R: This study was funded by Erasmus MC Rotterdam, Erasmus University Rotterdam and the Netherlands Organisation for Health Research and Development. V.W.V. Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). L. Duijts received funding from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 (696295; 2017), the Netherlands Organisation for Health Research and Development (ZonMw; 529051014; 2017), Science Foundation Ireland (SFI/16/ERA-HDHL/3360), and European Union (ALPHABET project). The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206, 2016; EUCAN-Connect 824989; ATHLETE, 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data or writing of this report. Generation XXI: Generation XXI was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education, and by the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020), Administração Regional de Saúde Norte (Regional Dept of Ministry of Health) and Fundação Calouste Gulbenkian. A.C. Santos is founded by FCT Investigator contracts IF/01060/2015. GINI: The GINIplus study was mainly supported for the first 3 years by the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum München (former GSF) (observational arm). The 4- and 6-year follow-up examinations of the GINIplus study were covered from the respective budgets of the five study centres (Helmholtz Zentrum München (former GSF), Research Institute at Marien-Hospital, Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf). HUMIS: We thank all mothers for participating in the HUMIS study. HUMIS was funded by a grant from the Norwegian Research Council (226402). The HUMIS study was approved by the Norwegian Data Inspectorate (2002/1398) and by the Regional Ethics Committee for Medical Research in Norway (S-02122), and the specific use in the current study was approved by the Ethics Committee as well (2010/1259/REK sør-øst). INMA: Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI09/00090, FIS-PI18/01142 including FEDER funds), CIBERESP, Dept of Health of the Basque Government (2013111089) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia and Beasain). Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2, PI061756; PS0901958, PI14/00677 including FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfemerdades Neurodegeneratives de La Caixa, and EC contract QLK4-CT-200-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 including FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241 and Fundació La marató de TV3 (090430). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. M. Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and cofunded by the European Social Fund “Investing in your future”. Valencia: This study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, UGP-15-249), and Alicia Koplowitz Foundation 2017. Isle of Wight: This study was funded by grants from the National Institutes of Health USA (R01HL082925), Asthma UK (364), Isle of Wight NHS Trust and the British Medical Association. KOALA: The collection of data relevant for this study was funded by grants from the Netherlands Organisation for Health Research and Development (ZonMw; 2100.0090) and the Netherlands Asthma Foundation (3.2.03.48, 3.2.07.022). The researchers are independent from the funders. The funders had no role in the study design, data analysis, interpretation of data or writing of this report. We thank the children and parents for their participation in the KOALA study. LRC (Leicestershire Respiratory Cohorts): This study was funded by grants from the Swiss National Science Foundation (SNF: 320030-182628, 320030-162820, 3233-069348, 3200-069349) and Asthma UK 07/048. Lifeways Cross-Generation Cohort Study: This study was funded by the Health Research Board, Ireland, and the Irish Dept of Health and Children's Health Promotion Policy Unit. LISA: The LISA study was mainly supported by grants from the Federal Ministry for Education, Science, Research and Technology and in addition from Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Bad Honnef for the first 2 years. The 4-, 6-, 10- and 15-year follow-up examinations of the LISA study were covered from the respective budgets of the involved partners (Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the Seventh Framework Program: MeDALL project. This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (949906). LucKi: LucKi is supported by Child and Youth Health Care Zuyderland, Public Health Service South Limburg and Maastricht University. We thank all parents and children for their participation in LucKi. LUKAS: This study was funded by research grants from the Academy of Finland (139021, 287675, 296814, 296817, 308254); Juho Vainio Foundation; EVO/VTR funding; Päivikki and Sakari Sohlberg Foundation; Farmers’ Social Insurance Institution (Mela); Finnish Cultural Foundation; Foundation for Pediatric Research; European Union QLK4-CT-2001-00250; and Finnish Institute for Health and Welfare, Finland. MAS-90: This study was funded by grants from the German Federal Ministry of Education and Research (MBMF; 07015633m 07ALE27, 01EE9405/5, 01EE9406) and the German Research Foundation (DFG; KE1462/2-1). Millennium Cohort Study: This study was funded by the Economic and Social Research Council and a consortium of UK government funders. We are grateful to the participating families and the Centre for Longitudinal Studies (CLS), UCL Institute of Education, for the use of these data and to the UK Data Service for making them available. However, neither CLS nor the UK Data Service bear any responsibility for the analysis or interpretation of these data. This work was supported by the Welcome Trust (187389/B/08/Z). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this ongoing cohort study. This research was supported by the Research Council of Norway through its Centres of Excellence funding scheme (262700). NINFEA: The authors are grateful to all the participants of the NINFEA cohort. The NINFEA study was partially funded by the Compagnia San Paolo Foundation. This research was partially funded by the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). PELAGIE: We are grateful to the families who participated and continue to participate in the study. The cohort is supported by INSERM and received funding from the French National Research Agency, Fondation de France, French Agency for Food, Environmental and Occupational Health & Safety, National Institute for Public Health Surveillance (InVS), French Ministry of Labour, and French Ministry of Ecology. PIAMA: This study was funded by the Netherlands Organisation of Health Research and Development, Netherlands Organisation for Scientific Research, Netherlands Asthma Fund, Netherlands Ministry of Spatial Planning, Housing and the Environment, and Netherlands Ministry of Health, Welfare and Sport. REPRO_PL: This study was funded by the National Science Center Poland (DEC-2014/15/B/N27/00998). Rhea: This study was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Program of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool age children in the prefecture of Heraklion, Crete, Greece”; MIS 349580, NSRF 2007–2013). Additional funding from the National Institute of Environmental Health Sciences (NIEHS) supported L. Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903, P30ES007048). STEPS: This study was funded by the University of Turku, Abo Akademi University, Turku University Hospital, Academy of Finland (123571, 140251, 277535) and Foundation for Pediatric Research Finland. SWS: This study was funded by the Medical Research Council, British Heart Foundation, Arthritis Research UK, Food Standards Agency, NIHR Southampton Biomedical Research Centre and the European Union's Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition (289346), and the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). WHISTLER: The WHISTLER birth cohort was supported with a grant from the Netherlands Organisation for Health Research and Development (2001-1-1322) and by an unrestricted grant from GlaxoSmithKline Netherlands. GlaxoSmithKline had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the report for publication. WHISTLER-Cardio was supported with an unrestricted strategic grant from the University Medical Center Utrecht (UMCU).

Published
2022

10. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: A meta-analysis of 150 000 European children

Author

van Meel, Evelien R, Mensink-Bout, Sara M, den Dekker, Herman T, Ahluwalia, Tarunveer S, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baïz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bønnelykke, Klaus, Carlsson, Christian J, Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchen, Karel, Eggesbø, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J, Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M, Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E, Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Mélen, Erik, Mehegan, John, Mommers, Monique, Nybo Andersen, Anne-Marie, Nystad, Wenche, Pedersen, Eva S L, Pekkanen, Juha, Peltola, Ville, Pike, Katharine C, Pinot de Moira, Angela, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S, Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C, Jaddoe, Vincent W V, Duijts, Liesbeth, van Meel, Evelien R, Mensink-Bout, Sara M, den Dekker, Herman T, Ahluwalia, Tarunveer S, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baïz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bønnelykke, Klaus, Carlsson, Christian J, Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchen, Karel, Eggesbø, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J, Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M, Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E, Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Mélen, Erik, Mehegan, John, Mommers, Monique, Nybo Andersen, Anne-Marie, Nystad, Wenche, Pedersen, Eva S L, Pekkanen, Juha, Peltola, Ville, Pike, Katharine C, Pinot de Moira, Angela, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S, Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C, Jaddoe, Vincent W V, and Duijts, Liesbeth

Abstract

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age.METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years.RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma.CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Published
2022

11. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: A meta-analysis of 150 000 European children

Author

IRAS OH Epidemiology Chemical Agents, van Meel, Evelien R, Mensink-Bout, Sara M, den Dekker, Herman T, Ahluwalia, Tarunveer S, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baïz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bønnelykke, Klaus, Carlsson, Christian J, Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchen, Karel, Eggesbø, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J, Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M, Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E, Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Mélen, Erik, Mehegan, John, Mommers, Monique, Nybo Andersen, Anne-Marie, Nystad, Wenche, Pedersen, Eva S L, Pekkanen, Juha, Peltola, Ville, Pike, Katharine C, Pinot de Moira, Angela, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S, Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C, Jaddoe, Vincent W V, Duijts, Liesbeth, IRAS OH Epidemiology Chemical Agents, van Meel, Evelien R, Mensink-Bout, Sara M, den Dekker, Herman T, Ahluwalia, Tarunveer S, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baïz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bønnelykke, Klaus, Carlsson, Christian J, Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchen, Karel, Eggesbø, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J, Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M, Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E, Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Mélen, Erik, Mehegan, John, Mommers, Monique, Nybo Andersen, Anne-Marie, Nystad, Wenche, Pedersen, Eva S L, Pekkanen, Juha, Peltola, Ville, Pike, Katharine C, Pinot de Moira, Angela, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S, Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C, Jaddoe, Vincent W V, and Duijts, Liesbeth

Published
2022

12. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children

Author

van Meel, Evelien R., Mensink-Bout, Sara M., den Dekker, Herman T., Ahluwalia, Tarunveer S., Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baiz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bonnelykke, Klaus, Carlsson, Christian J., Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchén, Karel, Eggesbo, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J., Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M., Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E., Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Melen, Erik, Mehegan, John, Mommers, Monique, Andersen, Anne-Marie Nybo, Nystad, Wenche, Pedersen, Eva S. L., Pekkanen, Juha, Peltola, Ville, Pike, Katharine C., de Moira, Angela Pinot, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S., Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C., Jaddoe, Vincent W. V., Duijts, Liesbeth, van Meel, Evelien R., Mensink-Bout, Sara M., den Dekker, Herman T., Ahluwalia, Tarunveer S., Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baiz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bonnelykke, Klaus, Carlsson, Christian J., Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchén, Karel, Eggesbo, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J., Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M., Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E., Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Melen, Erik, Mehegan, John, Mommers, Monique, Andersen, Anne-Marie Nybo, Nystad, Wenche, Pedersen, Eva S. L., Pekkanen, Juha, Peltola, Ville, Pike, Katharine C., de Moira, Angela Pinot, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S., Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C., Jaddoe, Vincent W. V., and Duijts, Liesbeth

Abstract

Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections., Funding Agencies|Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Swedish Child Diabetes Foundation (Barndiabetesfonden); JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden (FORSS); Swedish Council for Working Life and Social Research [FAS2004-1775]; Ostgota Brandstodsbolag; UK Medical Research Council; Wellcome [217065/Z/19/Z]; University of Bristol; Swedish Heart Lung Foundation; ALF Region Stockholm; SFO Epidemiology Karolinska Institutet; European Research Council [757919, ERC-2014-CoG-648916]; Programme Grants for Applied Research funding scheme [RP-PG-0407-10044]; Wellcome Trust [WT101597MA]; Swiss National Science Foundation [320030_163311, SNF: 320030-182628, 320030-162820, 3233-069348, 3200-069349]; Italian Ministry of Health; Lundbeck Foundation [R16-A1694, 195/04, R100-A9193, R264-2017-3099]; Ministry of Health [903516]; Danish Council for Strategic Research [0603-00280B]; Capital Region Research Foundation; Danish National Research Foundation; Danish Regional Committees; Egmont Foundation; March of Dimes Birth Defects Foundation; Novo Nordisk Foundation; Danish Medical Research Council [SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B]; Innovation Fund Denmark [0603-00294B (09-067124)]; Nordea Foundation [02-2013-2014]; University of Copenhagen; Danish Council for Independent Research [DFF-4183-00594, DFF-4183-00152]; Foundation for Medical Research (FRM); National Institute for Research in Public health; French Ministry of Health (DGS); French Ministry of Research; INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs; French National Institute for Health Education (INPES); European Union [733206]; Diabetes National Research Program; Mutuelle Generale de lEducation Nationale complementary health insurance (MGEN); French national agency for food security; European Community [261357]; Erasmus MC Rotterdam; Erasmus University Rotte

Published
2022
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13. Childhood asthma:pathogenesis and phenotypes

Author

Pijnenburg, Mariëlle W., Frey, Urs, De Jongste, Johan C., Saglani, Sejal, Pijnenburg, Mariëlle W., Frey, Urs, De Jongste, Johan C., and Saglani, Sejal

Abstract

In the pathogenesis of asthma in children there is a pivotal role for a type 2 inflammatory response to early life exposures or events. Interactions between infections, atopy, genetic susceptibility and environmental exposures (such as farmyard environment, air pollution and tobacco smoke exposure) influence the development of wheezing illness and the risk of progression to asthma. The immune system, lung function and the microbiome in gut and airways develop in parallel, and dysbiosis of the microbiome may be a critical factor in asthma development. Increased infant weight gain and preterm birth are other risk factors for development of asthma and reduced lung function. The complex interplay between these factors explains the heterogeneity of asthma in children. Subgroups of patients can be identified as phenotypes, based on clinical parameters, or endotypes, based on a specific pathophysiological mechanism. Paediatric asthma phenotypes and endotypes may ultimately help to improve diagnosis of asthma, prediction of asthma development and treatment of individual children, based on clinical, temporal, developmental or inflammatory characteristics. Unbiased, data-driven clustering, using a multidimensional or systems biology approach may be needed to better define phenotypes. The present knowledge on inflammatory phenotypes of childhood asthma has now been successfully applied in the treatment with biologicals of children with severe therapy-resistant asthma, and it is to be expected that more personalised treatment options may become available.

Published
2022

14. Associations of physical condition with lung function and asthma in adolescents from the general population

Author

Mensink-Bout, Sara M., Jahangir, Marc R., de Jongste, Johan C., Raat, Hein, Jaddoe, Vincent W.V., Duijts, Liesbeth, Mensink-Bout, Sara M., Jahangir, Marc R., de Jongste, Johan C., Raat, Hein, Jaddoe, Vincent W.V., and Duijts, Liesbeth

Abstract

Background: The relation of physical condition with respiratory outcomes in adolescents is unclear. We examined the hypothesis that adolescents with a lower physical condition represented by a lower cardiorespiratory fitness and physical activity, and a higher screen time have a lower lung function and higher risk of asthma. Methods: In a population-based prospective cohort study on 4854 children aged 13 years, we assessed cardiorespiratory fitness by using the peak work rate measured by the steep ramp test. Information on physical activity and screen time was obtained by self-reported questionnaires. Lung function was measured by spirometry and current asthma was assessed by a parental-reported questionnaire. Results: Taking sociodemographic, lifestyle, and growth-related confounders and multiple hypothesis testing into account, a 1 SD lower cardiorespiratory fitness was associated with a lower FEV1, FVC, and FEF75 (Z-score difference (95% CI): −0.31 (−0.35, −0.28), −0.30 (−0.33, −0.26), −0.13 (−0.17, −0.10), respectively), and a higher risk of asthma (Odds Ratio (95% CI) 1.25 (1.06, 1.46)). A 1 SD higher screen time was associated with a lower FVC (Z-score difference (95% CI): −0.06 (−0.10, −0.03)). Physical activity and screen time were not related to asthma. Results did not materially change after additional adjustment for respiratory outcomes at an earlier age. Conclusion: Adolescents with a lower cardiorespiratory fitness had a lower lung function and a higher risk of asthma. Those with a higher screen time had a lower FVC. Further studies are needed to explore the effect of improvements in physical condition on long-term respiratory outcomes.

Published
2022

15. Maternal diet in pregnancy and child’s respiratory outcomes:an individual participant data meta-analysis of 18 000 children

Author

Mensink-Bout, Sara M., van Meel, Evelien R., de Jongste, Johan C., Annesi-Maesano, Isabella, Aubert, Adrien M., Bernard, Jonathan Y., Chen, Ling Wei, Cooper, Cyrus, Crozier, Sarah, Hanke, Wojciech, Harvey, Nincholas C., Hebert, James R., Heude, Barbara, Jerzynska, Joanna, Kelleher, Cecily C., Mehegan, John, McAuliffe, Fionnuala M., Phillips, Catherine M., Polanska, Kinga, Relton, Caroline L., Shivappa, Nitin, Suderman, Matthew, Jaddoe, Vincent, Duijts, Liesbeth, Mensink-Bout, Sara M., van Meel, Evelien R., de Jongste, Johan C., Annesi-Maesano, Isabella, Aubert, Adrien M., Bernard, Jonathan Y., Chen, Ling Wei, Cooper, Cyrus, Crozier, Sarah, Hanke, Wojciech, Harvey, Nincholas C., Hebert, James R., Heude, Barbara, Jerzynska, Joanna, Kelleher, Cecily C., Mehegan, John, McAuliffe, Fionnuala M., Phillips, Catherine M., Polanska, Kinga, Relton, Caroline L., Shivappa, Nitin, Suderman, Matthew, Jaddoe, Vincent, and Duijts, Liesbeth

Abstract

Rationale Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health. Methods We performed an individual participant meta-analysis among 18 326 mother-child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energyadjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry. Results After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference -0.05, 95% CI -0.08- -0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <-1.64) (OR 1.20, 95% CI 1.06-1.36 and z-score difference 1.40, 95% CI 1.06-1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively. Conclusion The main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Published
2022

19. The Generation R Study: design and cohort update 2012

Author

Jaddoe, Vincent W. V., van Duijn, Cornelia M., Franco, Oscar H., van der Heijden, Albert J., van IIzendoorn, Marinus H., de Jongste, Johan C., van der Lugt, Aad, Mackenbach, Johan P., Moll, Henriëtte A., Raat, Hein, Rivadeneira, Fernando, Steegers, Eric A. P., Tiemeier, Henning, Uitterlinden, Andre G., Verhulst, Frank C., and Hofman, Albert

Published
2012

23. Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children

Author

Mensink-Bout, Sara M., primary, van Meel, Evelien R., additional, de Jongste, Johan C., additional, Annesi-Maesano, Isabella, additional, Aubert, Adrien M., additional, Bernard, Jonathan Y., additional, Chen, Ling-Wei, additional, Cooper, Cyrus, additional, Crozier, Sarah R., additional, Hanke, Wojciech, additional, Harvey, Nicholas C., additional, Hébert, James R., additional, Heude, Barbara, additional, Jerzynska, Joanna, additional, Kelleher, Cecily C., additional, Mehegan, John, additional, McAuliffe, Fionnuala M., additional, Phillips, Catherine M., additional, Polanska, Kinga, additional, Relton, Caroline L., additional, Shivappa, Nitin, additional, Suderman, Matthew, additional, Jaddoe, Vincent W.V., additional, and Duijts, Liesbeth, additional

Published
2021
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26. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J.P., Kreiner-Møller, Eskil, Kooijman, Marjolein N., Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P., Geller, Frank, Hayes, M. Geoffrey, Cousminer, Diana L., Körner, Antje, Thiering, Elisabeth, Curtin, John A., Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M., Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M., Teo, Yik-Ying, Barton, Sheila J., Evans, David M., Kemp, John P., St Pourcain, Beate, Ring, Susan M., Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D., Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M., Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C., Taal, H. Rob, Uitterlinden, André G., Armstrong, Loren L., Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R., Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M.T., Murray, Clare S., Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I., Buxton, Jessica L., Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S., Ang, Wei, Newnham, John P., Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T., Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I., Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N., Pers, Tune H., Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W., Melén, Erik, Grant, Struan F.A., Feenstra, Bjarke, Lowe, William L., Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H., Pennell, Craig E., Niinikoski, Harri, Dedoussis, George V., Mccarthy, Mark I., Frayling, Timothy M., Sunyer, Jordi, Timpson, Nicholas J., Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W.V.

Published
2015
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29. Association between nasal and nasopharyngeal bacterial colonization in early life and eczema phenotypes

Author

Hu, Chen, Duijts, Liesbeth, van Meel, Evelien R., Looman, Kirsten I.M., Kiefte-de Jong, Jessica C., Pardo, Luba M., Hijnen, Dirk Jan, Pasmans, Suzanne G.M.A., de Jongste, Johan C., Moll, Henriette A., Nijsten, Tamar, Hu, Chen, Duijts, Liesbeth, van Meel, Evelien R., Looman, Kirsten I.M., Kiefte-de Jong, Jessica C., Pardo, Luba M., Hijnen, Dirk Jan, Pasmans, Suzanne G.M.A., de Jongste, Johan C., Moll, Henriette A., and Nijsten, Tamar

Abstract

Background: An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and associations with other bacterial species are unclear.Objective: To examine the associations of early life nasal and nasopharyngeal bacterial carriage with eczema phenotypes, and the direction of any associations identified.Methods: Among 996 subjects of a population-based prospective cohort study, nasal swabs for Staphylococcus aureus, and nasopharyngeal swabs for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected and cultured from age 6 weeks to 6 years. Never, early, mid-, late transient and persistent eczema phenotypes were identified from parental-reported physician-diagnosed eczema from age 6 months until 10 years. Multinomial regression models and cross-lagged models were applied.Results: Staphylococcus aureus nasal carriage at 6 months was associated with an increased risk of early transient and persistent eczema (OR (95% CI): 2.69 (1.34, 5.39) and 4.17 (1.12, 15.51)). The associations between Staphylococcus aureus nasal carriage and eczema were mostly cross-sectional, and not longitudinal. No associations of Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal bacterial carriage with eczema and eczema phenotypes were observed (OR range (95% CI): 0.71 (0.35, 1.44) to 1.77 (0.84, 3.73)).Conclusions: Early life Staphylococcus aureus nasal carriage, but not Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal carriage, was associated with early transient and persistent eczema. Staphylococcus aureus nasal carriage and eczema were mostly cross-sectionally associated, and not longitudinally, making a causal relationship in either direction unlikely.

Published
2021

30. Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency:The Generation R Study

Author

Looman, Kirsten I.M., van Mierlo, Minke M.F., van Zelm, Menno C., Hu, Chen, Duijts, Liesbeth, de Jongste, Johan C., Nijsten, Tamar, Pardo, Luba M., Kiefte-de Jong, Jessica C., Moll, Henriëtte A., Pasmans, Suzanne G.M.A., Looman, Kirsten I.M., van Mierlo, Minke M.F., van Zelm, Menno C., Hu, Chen, Duijts, Liesbeth, de Jongste, Johan C., Nijsten, Tamar, Pardo, Luba M., Kiefte-de Jong, Jessica C., Moll, Henriëtte A., and Pasmans, Suzanne G.M.A.

Abstract

Background: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets. Methods: This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27+ and CD27- memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires. Results: FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets. Conclusions: School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population.

Published
2021

33. Correction: Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization (The Pharmacogenomics Journal, (2020), 20, 5, (621-628), 10.1038/s41397-019-0140-y)

Author

King, Charlotte, McKenna, Amanda, Farzan, Niloufar, Vijverberg, Susanne J., van der Schee, Marc P., Maitland-van der Zee, Anke H., Arianto, Lambang, Bisgaard, Hans, BØnnelykke, Klaus, Berce, Vojko, PotoČnik, Uros, Repnik, Katja, Carleton, Bruce, Daley, Denise, Chew, Fook Tim, Chiang, Wen Chin, Sio, Yang Yie, Cloutier, Michelle M., den Dekker, Herman T., Duijts, Liesbeth, de Jongste, Johan C., Dijk, F. Nicole, Flores, Carlos, Hernandez-Pacheco, Natalia, Mukhopadhyay, Somnath, Basu, Kaninika, Tantisira, Kelan G., Verhamme, Katia M., Celedón, Juan C., Forno, Erick, Canino, Glorisa, Francis, Ben, Pirmohamed, Munir, Sinha, Ian, Hawcutt, Daniel B., Pulmonology, AII - Inflammatory diseases, APH - Personalized Medicine, and Paediatric Pulmonology

Abstract

The original version of this article did not include Juan C. Celedón, Erick Forno and Glorisa Canino in the list of authors and incorrectly cited Gerard H. Koppelman, Maria Pino-Yanes and Steve Turner as authors. This has now been corrected in both the PDF and HTML versions of the article.

Published
2020

34. Hair cortisol and inhaled corticosteroid use in asthmatic children

Author

Baan, Esmé J, van den Akker, Erica L T, Engelkes, Marjolein, de Rijke, Yolanda B, de Jongste, Johan C, Sturkenboom, Miriam C J M, Verhamme, Katia M, Janssens, Hettie M, Baan, Esmé J, van den Akker, Erica L T, Engelkes, Marjolein, de Rijke, Yolanda B, de Jongste, Johan C, Sturkenboom, Miriam C J M, Verhamme, Katia M, and Janssens, Hettie M

Published
2020

36. Pharmacogenomic associations of adverse drug reactions in asthma:systematic review and research prioritisation

Author

King, Charlotte, McKenna, Amanda, Farzan, Niloufar, Vijverberg, Susanne J., van der Schee, Marc P., Maitland-van der Zee, Anke H., Arianto, Lambang, Bisgaard, Hans, BØnnelykke, Klaus, Berce, Vojko, Potočnik, Uroš, Repnik, Katja, Carleton, Bruce, Daley, Denise, Chew, Fook Tim, Chiang, Wen Chin, Sio, Yang Yie, Cloutier, Michelle M., Den Dekker, Herman T., Duijts, Liesbeth, de Jongste, Johan C., Dijk, F. Nicole, Koppelman, Gerard H., Flores, Carlos, Hernandez-Pacheco, Natalia, Pino-Yanes, Maria, Mukhopadhyay, Somnath, Basu, Kaninika, Bignell, Lauren, Tantisira, Kelan G., Turner, Steve, Verhamme, Katia M., Francis, Ben, Pirmohamed, Munir, Sinha, Ian, Hawcutt, Daniel B., King, Charlotte, McKenna, Amanda, Farzan, Niloufar, Vijverberg, Susanne J., van der Schee, Marc P., Maitland-van der Zee, Anke H., Arianto, Lambang, Bisgaard, Hans, BØnnelykke, Klaus, Berce, Vojko, Potočnik, Uroš, Repnik, Katja, Carleton, Bruce, Daley, Denise, Chew, Fook Tim, Chiang, Wen Chin, Sio, Yang Yie, Cloutier, Michelle M., Den Dekker, Herman T., Duijts, Liesbeth, de Jongste, Johan C., Dijk, F. Nicole, Koppelman, Gerard H., Flores, Carlos, Hernandez-Pacheco, Natalia, Pino-Yanes, Maria, Mukhopadhyay, Somnath, Basu, Kaninika, Bignell, Lauren, Tantisira, Kelan G., Turner, Steve, Verhamme, Katia M., Francis, Ben, Pirmohamed, Munir, Sinha, Ian, and Hawcutt, Daniel B.

Abstract

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

Published
2020

37. Hair cortisol and inhaled corticosteroid use in asthmatic children

Author

Global Health, JC onderzoeksprogramma Infectieziekten, Baan, Esmé J, van den Akker, Erica L T, Engelkes, Marjolein, de Rijke, Yolanda B, de Jongste, Johan C, Sturkenboom, Miriam C J M, Verhamme, Katia M, Janssens, Hettie M, Global Health, JC onderzoeksprogramma Infectieziekten, Baan, Esmé J, van den Akker, Erica L T, Engelkes, Marjolein, de Rijke, Yolanda B, de Jongste, Johan C, Sturkenboom, Miriam C J M, Verhamme, Katia M, and Janssens, Hettie M

Published
2020

38. Exploratory Study of Signals for Asthma Drugs in Children, Using the EudraVigilance Database of Spontaneous Reports

Author

Global Health, JC onderzoeksprogramma Infectieziekten, Baan, Esmé J, de Smet, Veronique A, Hoeve, Christina E, Pacurariu, Alexandra C, Sturkenboom, Miriam C J M, de Jongste, Johan C, Janssens, Hettie M, Verhamme, Katia M C, Global Health, JC onderzoeksprogramma Infectieziekten, Baan, Esmé J, de Smet, Veronique A, Hoeve, Christina E, Pacurariu, Alexandra C, Sturkenboom, Miriam C J M, de Jongste, Johan C, Janssens, Hettie M, and Verhamme, Katia M C

Published
2020

39. The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health:A population-based prospective cohort study

Author

van Meel, Evelien R., Jaddoe, Vincent W.V., Reiss, Irwin K.M., van Zelm, Menno C., de Jongste, Johan C., Moll, Henriëtte A., Duijts, Liesbeth, van Meel, Evelien R., Jaddoe, Vincent W.V., Reiss, Irwin K.M., van Zelm, Menno C., de Jongste, Johan C., Moll, Henriëtte A., and Duijts, Liesbeth

Abstract

Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection are common in early childhood. CMV infection favours a T-helper-1 and EBV infection a T-helper-2 cell response, possibly leading to disbalanced T-helper cell response, and subsequent risk of asthma or atopy. Objective: To study the associations of EBV and CMV with lung function, asthma and inhalant allergic sensitization at school age. Methods: This study among 3546 children was embedded in a population-based prospective cohort. At age 6 years, serum IgG levels against EBV and CMV were measured by ELISA. At age 10 years, lung function was measured by spirometry, asthma by questionnaire and inhalant allergic sensitization by skin prick test. Results: Unadjusted models showed that seropositivity for EBV was associated with a higher FEV1 and FEF75 (Z-score difference (95% CI): 0.09 (0.02, 0.16) and 0.09 (0.02, 0.15)), while seropositivity for CMV was not. Specific combinations of viruses showed that seropositivity for EBV was only associated with FEV1 and FEF75 in the presence of seropositivity for CMV (0.12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI): 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. Conclusions and Clinical Relevance: Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors.

Published
2020

40. Risk factors for intensive care admission in children with severe acute asthma in the Netherlands: a prospective multicentre study

Author

Intensive care patientenzorg, Child Health, Boeschoten, Shelley A, Boehmer, Annemie L, Merkus, Peter J, van Rosmalen, Joost, de Jongste, Johan C, Fraaij, Pieter L A, Molenkamp, Richard, Heisterkamp, Sabien G, van Woensel, Job B, Kapitein, Berber, Haarman, Eric G, Wösten-van Asperen, Roelie M, Kneyber, Martin C, Lemson, Joris, Hartman, Stan, van Waardenburg, Dick A, Bunker-Wiersma, Heleen E, Brouwer, Carole N, van Ewijk, Bart E, Landstra, Anneke M, Verwaal, Mariel, Vaessen-Verberne, Anja A, Hammer, Sanne, Buysse, Corinne M, de Hoog, Matthijs, Intensive care patientenzorg, Child Health, Boeschoten, Shelley A, Boehmer, Annemie L, Merkus, Peter J, van Rosmalen, Joost, de Jongste, Johan C, Fraaij, Pieter L A, Molenkamp, Richard, Heisterkamp, Sabien G, van Woensel, Job B, Kapitein, Berber, Haarman, Eric G, Wösten-van Asperen, Roelie M, Kneyber, Martin C, Lemson, Joris, Hartman, Stan, van Waardenburg, Dick A, Bunker-Wiersma, Heleen E, Brouwer, Carole N, van Ewijk, Bart E, Landstra, Anneke M, Verwaal, Mariel, Vaessen-Verberne, Anja A, Hammer, Sanne, Buysse, Corinne M, and de Hoog, Matthijs

Published
2020

46. Risk factors for intensive care admission in children with severe acute asthma in the Netherlands: a prospective multicentre study

Author

Boeschoten, Shelley A., primary, Boehmer, Annemie L., additional, Merkus, Peter J., additional, van Rosmalen, Joost, additional, de Jongste, Johan C., additional, Fraaij, Pieter L.A., additional, Molenkamp, Richard, additional, Heisterkamp, Sabien G., additional, van Woensel, Job B., additional, Kapitein, Berber, additional, Haarman, Eric G., additional, Wösten-van Asperen, Roelie M., additional, Kneyber, Martin C., additional, Lemson, Joris, additional, Hartman, Stan, additional, van Waardenburg, Dick A., additional, Bunker-Wiersma, Heleen E., additional, Brouwer, Carole N., additional, van Ewijk, Bart E., additional, Landstra, Anneke M., additional, Verwaal, Mariel, additional, Vaessen-Verberne, Anja A., additional, Hammer, Sanne, additional, Buysse, Corinne M., additional, and de Hoog, Matthijs, additional

Published
2020
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