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Adam Messinger, Sean Froudist-Walsh, Doris Y. Tsao, Wim Vanduffel, Jean-François Aubry, Richard J. Krauzlis, Melanie Wilke, Angela C. Roberts, Béchir Jarraya, Hiroyuki Oya, Igor Kagan, Andrew S. Fox, Michael Ortiz-Rios, Charles E. Schroeder, P. Christiaan Klink, Anna S. Mitchell, Lynn Uhrig, Elisa E. Konofagou, Vincent P. Ferrera, Michael C. Schmid, Christopher I. Petkov, Jerome Sallet, Matthew F. S. Rushworth, Anna W. Roe, Jordy Tasserie, HAL UVSQ, Équipe, Equipements d'excellence - Thérapie et Neurostimulation cérébrale de très haute précision par Ultrasons Transcraniens - - ULTRABRAIN2010 - ANR-10-EQPX-0015 - EQPX - VALID, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Physique pour la médecine (PhysMed Paris), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], University of California [Davis] (UC Davis), University of California (UC), New York University [New York] (NYU), NYU System (NYU), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], National Eye Institute [Bethesda, MD, États-Unis] (NEI), National Institutes of Health [Bethesda] (NIH), National Institute of Mental Health (NIMH), University of Oxford, Leibniz Institute for Primate Research, German Primate Centre, Institute for Cell and Molecular Biosciences, The Medical School Newcastle University, University of Northumbria at Newcastle [United Kingdom], University of Iowa [Iowa City], University of Cambridge [UK] (CAM), Zhejiang Gongshang University [Hangzhou] (ZJSU), Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Fribourg, Howard Hughes Medical Institute (HHMI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Harvard Medical School [Boston] (HMS), Massachusetts General Hospital [Boston], University Medical Center Göttingen (UMG), German Primate Center - Deutsches Primatenzentrum -- Leibniz Insitute for Primate Research -- [Göttingen, Allemagne] (GPC - DPZ), Newcastle University [Newcastle], 2015AA020515, IDEX/IMP/2020/14 MECHIDENT 724198 945539 G0B8617N, G0C1920N, G0E0520N, VS02219N ZIA EY000511 637638 National Science Foundation, NSF: 2020C03004, 31627802, 81430010 National Institutes of Health, NIH: MH112142 Howard Hughes Medical Institute, HHMI National Institute of Mental Health, NIMH: ZIA MH002918 California National Primate Research Center, CNPRC: P51-OD011107 Wellcome Trust, WT: WT 110157/Z/15/Z European Research Council, ERC Deutsche Forschungsgemeinschaft, DFG: GA1475-B4, KA 3726/2-1, WI 4046/1-1, WT092606AIA Agence Nationale de la Recherche, ANR: ANR-10-EQPX-15, R01-DC04290 KU Leuven: C14/17/109 Fondation Bettencourt Schueller National Key Research and Development Program of China, NKRDPC: 2018YFA0701400, This work was supported by NIH -MH112142 (V.F. and E.K.), California National Primate Research Center Base Grant ( P51-OD011107 ) (A.F.), Fondation Bettencourt Schueller, France and Human Brain Project (B.J., L.U., J.T.), the Intramural Research Program of the NIMH (ZIA MH002918) (A.M.), Wellcome Trust ( WT 110157/Z/15/Z ) (A.S.M.), European Research Council (ERC StG, OptoVision, 637638 ) (M.C.S and M.O.R.), National Key R&D Program of China 2018YFA0701400 (A.W.R.), Chinese NSF ( 81430010 and 31627802 ) (A.W.R.), Zhejiang province 2020C03004 (A.W.R.), Chinese National R&D Program Grant 2015AA020515 (A.W.R.), IDEXLYON 'IMPULSION 2020 grant (IDEX/IMP/2020/14) (J.S.), Howard Hughes Medical Institute (D.T.), KU Leuven grant C14/17/109 (W.V.), the National Eye Institute Intramural Research Program (ZIA EY000511 ) at the National Institutes of Health, U.S.A. (W.V.), Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO) G0D5817N , G0B8617N , G0C1920N , G0E0520N , VS02219N (W.V.), the European Union's Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No 945539 (Human Brain Project SGA3) (W.V.), Hermann and Lilly Schilling Foundation, German Research Foundation (DFG) grants WI 4046/1-1 and Research Unit GA1475-B4, KA 3726/2-1, Primate Platform of DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB) (M.W. and I.K.), Wellcome Trust ( WT092606AIA ) (C.I.P.), European Research Council Horizon 2020 (ERC CoG, MECHIDENT 724198) (C.I.P.), the Bettencourt Schueller Foundation (Ultrabrain project) (J.-F. A.), the French National Agency for Research ( ANR-10-EQPX-15 ) (J.-F. A.):and the National Institutes of Health (with Matthew Howard III: R01-DC04290 ) (C.I.P.), This work was supported by NIH-MH112142 (V.F. and E.K.), California National Primate Research Center Base Grant (P51-OD011107) (A.F.), Fondation Bettencourt Schueller, France and Human Brain Project (B.J. L.U. J.T.), Wellcome Trust (WT 110157/Z/15/Z) (A.S.M.), European Research Council (ERC StG, OptoVision, 637638) (M.C.S and M.O.R.), Chinese NSF (81430010 and 31627802) (A.W.R.), IDEXLYON ?IMPULSION 2020 grant (IDEX/IMP/2020/14) (J.S.), the National Eye Institute Intramural Research Program (ZIA EY000511) at the National Institutes of Health, U.S.A. (W.V.), Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO) G0D5817N, G0B8617N, G0C1920N, G0E0520N, VS02219N (W.V.), Wellcome Trust (WT092606AIA) (C.I.P.), the French National Agency for Research (ANR-10-EQPX-15) (J.-F. A.):and the National Institutes of Health (with Matthew Howard III: R01-DC04290) (C.I.P.), All research discussed in this work was performed in accordance with institutional and nationally approved oversight, such as the NIH Guide for Care and Use of Laboratory Animals, the U.K. Animals (Scientific Procedures) Act, 1986, and European Directive 2010/63/EU., ANR-10-EQPX-0015,ULTRABRAIN,Thérapie et Neurostimulation cérébrale de très haute précision par Ultrasons Transcraniens(2010), Institut cellule souche et cerveau (SBRI), Université de Fribourg = University of Fribourg (UNIFR), Physique pour la médecine (UMR 8063, U1273), University of California, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Isabelle Pin, Isa Cerveri, Lucia Cazzoletti, Andrei Malinovschi, Josep M. Antó, Simone Accordini, Deborah Jarvis, David Gislason, Ane Johannessen, Bénédicte Leynaert, Pierpaolo Marchetti, Diogenes S. Ferreira, Nicole Probst-Hensch, Alessandro Marcon, Christer Janson, Rain Jögi, Judith Garcia-Aymerich, Angelo Corsico, Joachim Heinrich, Joost Weyler, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 2610, 4350 97/0035-01, 99/0034-01, 99/0034-02 97/0035, 97/0035-02, 99/0034-04, 99/0034-06, 99/0034-07, 99/350 90MR/10, 91AF/6 SEPAR R01 HL62633-01 018996 911631 Russell Sage Foundation, RSF ResMed Foundation AstraZeneca GlaxoSmithKline, GSK Novartis U.S. Public Health Service, USPHS: R01 HL62633-01 Chiesi Farmaceutici, Chiesi Faculty of Arts and Sciences, Harvard University, FAS Boehringer Ingelheim VÃ¥rdalstiftelsen Freiwillige Akademische Gesellschaft, FAG Commercial Aircraft of China, COMAC Wellcome Trust, WT: WT 084703MA Horizon 2020 Framework Programme, H2020: 633212 Growing Spine Foundation, GSF Gobierno del Principado de Asturias Blond McIndoe Research Foundation, BMRF Asthma and Allergy Foundation of America, AAFA Ministerio de Sanidad, Consumo y Bienestar Social, MISAN Union Chimique Belge, UCB Medical Research Council, MRC: 92091, G0901214 National Institute for Health Research, NIHR British Lung Foundation, BLF European Commission, EC: EU-PEAL PL01237 National Health and Medical Research Council, NHMRC: G.0402.00 Asthma Foundation of Victoria Deutsche Forschungsgemeinschaft, DFG: FR1526/1-1, HE 3294/10-1, MA 711/4-1, MA 711/6-1, NO 262/7-1 Agence Nationale de la Recherche, ANR Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNSF: 3100-059302, 3200-042532, 3200-052720, 3247-065896, 3247BO-104283, 3247BO-104284, 3247BO-104288, 33CSCO-108796, 33CSCO-134276/1, 4026-028099, 4026-28099 Eesti Teadusfondi, ETF: 1088 ForskningsrÃ¥det för Arbetsliv och Socialvetenskap, FAS Eesti Teadusagentuur: 562 Bundesamt für Gesundheit, BAG Belgian Federal Science Policy Office, BELSPO Generalitat de Catalunya Consell Català de Recerca i Innovació: 1999SGR 00241 Haridus- ja Teadusministeerium: SF0180060s09 Hjärt-Lungfonden Consiglio Nazionale delle Ricerche, CNR Instituto de Salud Carlos III, ISCIII: C03/011, C03/09 Háskóli Íslands, HI Norges ForskningsrÃ¥d: 101422/310, 214123 Medicinska ForskningsrÃ¥det, MFR Cancéropôle Ile de France Russian Science Foundation, RSF: 381/05.93 Ministeriet Sundhed Forebyggelse SUVA Sociedad Española de Neumología y Cirugía Torácica, SEPAR: FIS 09/01511, FIS PS09/00716, FIS PS09/02185, FIS PS09/03190, SEPAR 1001/2010 Horizon 2020 Universiteit Antwerpen Comité des Maladies Respiratoires de l'Isère Comissió Interdepartamental de Recerca i Innovació Tecnològica, CIRIT: 1997 SGR 00079, 1999 SGR 00214 Servicio Murciano de Salud Regione del Veneto Regione Piemonte Astma- och Allergiförbundet Centre Hospitalier Universitaire de Bordeaux, CHU de Bordeaux Office Fédéral de l'Education et de la Science, OFES Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, BMBWF Helmholtz Zentrum München Lungenliga Schweiz Ministerio de Medio Ambiente y Medio Rural y Marino, MARM: G03/176 Ministère des Solidarités et de la Santé INCLIVA Instituto de Investigación Sanitaria: 91/0016-060-05/E, 92/0319, 93/0393, PS09/00716, PS09/01511, PS09/02185, PS09/02457, PS09/03190 Fundació Autònoma Solidària, FAS Servicio Andaluz de Salud, SAS, The ALEC study is funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org. The funders had no role in the writing of the manuscript or the decision to submit it for publication.Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria, Allen and Hanburys, National Health and Medical Research Council. I. Pin reports travel grants and honoraria from Novartis, Zambon, and AstraZeneca, and nonfinancial support from AGIR?dom. R. J?gi reports grants from Estonian Research Council Personal Research (grant no. 562), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.Financial support for ECRHS I: The coordination of this work was supported by the European Commission, and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria, Allen and Hanbury's, Belgium: Belgian Science Policy Office, National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088), France: Minist?re de la Sant?, Glaxo France, Institut Pneumologique d'Aquitaine, Contrat de Plan Etat-R?gion Languedoc-Rousillon, Caisse nationale de l'assurance maladie des travailleurs salari?s, Comit? national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegu? de la sant?, R?seau national de sant? publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister f?r Forschung und Technologie, Italy: Ministero dell'Universit? e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93), Norway: Norwegian Research Council project no. 101422/310, Portugal: Glaxo Farmac?utica Lda, Sandoz Portugesa, Spain: Fondo de Investigaci?n Sanitaria (nos. 91/0016-060-05/E, 92/0319, and 93/0393), Hospital General de Albacete, Hospital General Juan Ram?n Jim?nez, Direcci?n Regional de Salud P?blica (Consejer?a de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovaci? Tecnol?gica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council, the Swedish Heart-Lung Foundation, the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099), and UK: National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority.Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00), University of Antwerp, and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350), France: (All) Programme Hospitalier de Recherche Clinique?Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health, Minist?re de l'Emploi et de la Solidarit?, Direction G?nerale de la Sant?, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d'Aquitaine, Grenoble: Comite des Maladies Respiratoires de l'Isere, Montpellier: Aventis (France), Direction Regionale des Affaires Sanitaires et Sociales Languedoc-Roussillon, Paris: Union Chimique Belge-Pharma (France), Aventis (France), Glaxo France, Germany: Erfurt: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code FR1526/1-1), Hamburg: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code MA 711/4-1), Iceland: Reykjavik: Icelandic Research Council and Icelandic University Hospital Fund, Italy: Pavia: GlaxoSmithKline Italy, Italian Ministry of University and Scientific and Technological Research (MURST), and Local University Funding for Research 1998 and 1999, Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico?Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell'Universit? e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council, Norwegian Asthma and Allergy Association, Glaxo Wellcome AS, and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumolog?a y Cirug?a Toracica, Public Health Service (grant code R01 HL62633-01), Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Consell Interdepartamentalde Recerca i Innovaci? Tecnol?gica (grant code 1999SGR 00241), Instituto de Salud Carlos III, Red de Centros de Epidemiolog?a y Salud P?blica, C03/09, Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Galdakao: Basque Health Department, Oviedo: Fondo de Investigaciones Sanitaria (97/0035-02, 97/0035, 99/0034-01, 99/0034-02, 99/0034-04, 99/0034-06, 99/350, and 99/0034-07), European Commission (EU-PEAL PL01237), Generalitat de Catalunya (CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Espa?ola de Neumolog?a y Cirug?a Tor?cica (SEPAR R01 HL62633-01), Red de Centros de Epidemiolog?a y Salud P?blica (C03/09), Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, 97/0035-01, 99/0034-01, and 99/0034-02), Sweden: G?teborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research, Swedish Asthma and Allergy Foundation, Swedish Cancer and Allergy Foundation, and Swedish Council for Working Life and Social Research (FAS), Switzerland: Basel: Swiss National Science Foundation, Swiss Federal Office for Education and Science, and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign).Financial support for ECRHS III: Australia: National Health and Medical Research Council, Belgium: Antwerp: South and Antwerp City: Research Foundation Flanders (grant code G.0.410.08.N.10), Estonia: Tartu: the Estonian Ministry of Education (SF0180060s09), France: (All): Minist?re de la Sant?, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Universit? Bordeaux segalen, Grenoble: Comite Scientifique AGIRadom 2011, and Paris: Agence Nationale de la Sant?, R?gion Ile de France, domaine d'int?r?t majeur, Germany: Erfurt: German Research Foundation (HE 3294/10-1), Hamburg: German Research Foundation (MA 711/6-1, NO 262/7-1), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation, California, USA, Orkuveita Reykjavikur (Geothermal plant), and Vegager?in (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health, Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Universit? e della Ricerca), Norway: Norwegian Research Council (grant no. 214123), Western Norway Regional Health Authorities (grant no. 911631), and Blond McIndoe Research Foundation, Spain: Fondo de Investigaci?n Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Espa?ola de Neumolog?a y Cirurg?a Tor?cica (SEPAR 1001/2010), Fondo de Investigaci?n Sanitaria (PS09/02457), Barcelona: Fondo de Investigaci?n Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigaci?n Sanitaria (FIS 09/01511), Huelva: Fondo de Investigaci?n Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigaci?n Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association, The Swedish Association against Lung and Heart Disease, Swedish Research Council for health, working life and welfare, G?teborg: also received further funding from the Swedish Council for Working Life and Social Research. Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, and 4026-028099), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Z?rich, the Swiss Lung League, the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no.92091), support also provided by the National Institute for Health Research through the Primary Care Research Network., Financial support for ECRHS III: Australia: National Health and Medical Research Council, Estonia: Tartu: the Estonian Ministry of Education ( SF0180060s09 ), France: (All): Ministère de la Santé, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Université Bordeaux segalen, and Paris: Agence Nationale de la Santé, Région Ile de France, domaine d'intérêt majeur, Germany: Erfurt: German Research Foundation ( HE 3294/10-1 ), Hamburg: German Research Foundation ( MA 711/6-1 , NO 262/7-1 ), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation , California, USA , Orkuveita Reykjavikur (Geothermal plant), and Vegagerðin (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health , Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Università e della Ricerca), Norway: Norwegian Research Council (grant no. 214123 ), Western Norway Regional Health Authorities (grant no. 911631 ), and Blond McIndoe Research Foundation, Spain: Fondo de Investigación Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Española de Neumología y Cirurgía Torácica ( SEPAR 1001/2010), Fondo de Investigación Sanitaria (PS09/02457), Barcelona: Fondo de Investigación Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigación Sanitaria (FIS 09/01511), Huelva: Fondo de Investigación Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigación Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association , The Swedish Association against Lung and Heart Disease , Swedish Research Council for health, working life and welfare, Göteborg: also received further funding from the Swedish Council for Working Life and Social Research . Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1 , 33CSCO-108796 , 3247BO-104283 , 3247BO-104288 , 3247BO-104284 , 3247-065896 , 3100-059302 , 3200-052720 , 3200-042532 , and 4026-028099 ), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League , the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft , UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics , European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no. 92091 ), support also provided by the National Institute for Health Research through the Primary Care Research Network ., Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria , Allen and Hanburys , National Health and Medical Research Council . I. Pin reports travel grants and honoraria from Novartis , Zambon , and AstraZeneca , and nonfinancial support from AGIRàdom. R. Jõgi reports grants from Estonian Research Council Personal Research (grant no. 562 ), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00 ), University of Antwerp , and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350 ), France: (All) Programme Hospitalier de Recherche Clinique—Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health , Ministère de l’Emploi et de la Solidarité, Direction Génerale de la Santé, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d’Aquitaine, Grenoble: Comite des Maladies Respiratoires de l’Isere, Germany: Erfurt: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code FR1526/1-1 ), Hamburg: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code MA 711/4-1 ), Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico—Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell’Università e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council , Norwegian Asthma and Allergy Association , Glaxo Wellcome AS , and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumología y Cirugía Toracica, Public Health Service (grant code R01 HL62633-01 ), Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Consell Interdepartamentalde Recerca i Innovació Tecnológica (grant code 1999SGR 00241 ), Instituto de Salud Carlos III, Red de Centros de Epidemiología y Salud Pública, C03/09, Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Oviedo: Fondo de Investigaciones Sanitaria ( 97/0035-02 , 97/0035 , 99/0034-01 , 99/0034-02 , 99/0034-04 , 99/0034-06 , 99/350 , and 99/0034-07 ), European Commission ( EU-PEAL PL01237 ), Generalitat de Catalunya ( CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Española de Neumología y Cirugía Torácica ( SEPAR R01 HL62633-01 ), Red de Centros de Epidemiología y Salud Pública (C03/09), Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, Sweden: Göteborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research , Swedish Asthma and Allergy Foundation , Swedish Cancer and Allergy Foundation , and Swedish Council for Working Life and Social Research ( FAS ), Switzerland: Basel: Swiss National Science Foundation , Swiss Federal Office for Education and Science , and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign)., Financial support for ECRHS I: The coordination of this work was supported by the European Commission , and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria , Allen and Hanbury's, Belgium: Belgian Science Policy Office , National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088 ), France: Ministère de la Santé, Glaxo France , Institut Pneumologique d'Aquitaine , Contrat de Plan Etat-Région Languedoc-Rousillon , Caisse nationale de l'assurance maladie des travailleurs salariés, Comité national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegué de la santé, Réseau national de santé publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister für Forschung und Technologie, Italy: Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93 ), Portugal: Glaxo Farmacêutica Lda, Sandoz Portugesa, Spain: Fondo de Investigación Sanitaria (nos. 91/0016-060-05/E , 92/0319 , and 93/0393 ), Hospital General de Albacete, Hospital General Juan Ramón Jiménez, Dirección Regional de Salud Pública (Consejería de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovació Tecnològica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council , the Swedish Heart-Lung Foundation , the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099 ), and UK: National Asthma Campaign , British Lung Foundation , Department of Health , South Thames Regional Health Authority ., The ALEC study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org . The funders had no role in the writing of the manuscript or the decision to submit it for publication., Commission of the European Communities, Medical Research Council (MRC), and Ageing Lungs European Cohorts ALEC

Jannasch, Franziska, Dietrich, Stefan, Bishop, Tom RP, Pearce, Matthew, Fanidi, Anouar, O'Donoghue, Gráinne, O'Gorman, Donal, Marques-Vidal, Pedro, Vollenweider, Peter, Bes-Rastrollo, Maira, Byberg, Liisa, Wolk, Alicja, Hashemian, Maryam, Malekzadeh, Reza, Poustchi, Hossein, Luft, Vivian C, De Matos, Sheila M Alvim, Kim, Jihye, Kim, Mi Kyung, Kim, Yeonjung, Stern, Dalia, Lajous, Martin, Magliano, Dianna J, Shaw, Jonathan E, Akbaraly, Tasnime, Kivimaki, Mika, Maskarinec, Gertraud, Le Marchand, Loïc, Martínez-González, Miguel Ángel, Soedamah-Muthu, Sabita S, EPIC-InterAct Consortium, Wareham, Nicholas J, Forouhi, Nita G, Schulze, Matthias B, Medical and Clinical Psychology, Jannasch, Franziska [0000-0003-3478-4758], Apollo - University of Cambridge Repository, EPIC-InterAct Consortium, University of Cambridge [UK] (CAM), Université de Lausanne = University of Lausanne (UNIL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G03/140, PI10/02293, PI10/02658, PI13/00615, PI14/01668, PI14/01764, PI14/01798, PI17/01795, PI20/00564, PNSD-2020/021, LSHM_CT_2006_037197, 82DZD00302, 122/2014, 27/2011, 45/2011, PNSD 2020/2021, FKZ: 01EA1806A, National Institutes of Health, NIH: R01AG056477, RF1AG062553, U01 CA164973, National Cancer Institute, NCI, American Institute for Cancer Research, AICR: 05B047, GlaxoSmithKline, GSK, Centre International de Recherche sur le Cancer, CIRC, Wellcome Trust, WT: 221854/Z/20/Z, Horizon 2020 Framework Programme, H2020: 824989, Seventh Framework Programme, FP7: 602068, Manchester Biomedical Research Centre, BRC: IS-BRC-1215-20014, Medical Research Council, MRC: MC_UU_00006/1and MC_UU_00006/3, Cancer Research UK, CRUK: C20/A5860, National Research Foundation, NRF, Department of Science and Technology, Ministry of Science and Technology, India, डीएसटी, Deutsche Forschungsgemeinschaft, DFG: 491394008, NFDI 13/1, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF: 33CS30-139468, 33CS30-148401, 33CS30_177535/1, 33CSCO-122661, MRCMR/R024227/1, Bundesministerium für Bildung und Forschung, BMBF, Consejo Nacional de Ciencia y Tecnología, CONACYT: S0008-2009-1: 000000000115312, Kementerian Sains, Teknologi dan Inovasi, MOSTI, Nederlandse Zuivel Organisatie, NZO, Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Ministry of Science, ICT and Future Planning, MSIP: NRF-2017M3C9A6047623, Ministry of Health and Welfare, MOHW: 4845-301, 4851-302, Korea Centers for Disease Control and Prevention, KCDC, Seconda Università degli Studi di Napoli, SUN, Vetenskapsrådet, VR: 2017–00644, Universidad de Navarra, Tehran University of Medical Sciences and Health Services, TUMS: 81/15, Financiadora de Estudos e Projetos, FINEP: 01 06 0010.00, 01 06 0071.00, 01 06 0115.00, 01 06 0300.00, Ministério da Saúde, Mejeribrugets ForskningsFond, MFF, European Regional Development Fund, ERDF: RD 06/0045, Open Access funding enabled and organized by Projekt DEAL. The InterConnect project is funded by the European Union’s Seventh Framework Programme (grant number 602068). FJ and MBS acknowledge funding from the German Federal Ministry of Education and Research and the State of Brandenburg to the German Center for Diabetes Research (DZD) (82DZD00302). Furthermore, this work was supported by the NutriAct – Competence Cluster Nutrition Research Berlin-Potsdam funded by the German Federal Ministry of Education and Research (FKZ: 01EA1806A). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491394008. This work was done as part of the NFDI4Health Consortium ( www.nfdi4health.de ). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – NFDI 13/1. NJW and NGF acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_00006/1and MC_UU_00006/3) and NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). NGF is an NIHR Senior Investigator (G111539). TB acknowledges funding from EUCAN-Connect under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 824989). The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197). MBR and MAMG acknowledge that the SUN Project has received funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), PNSD-2020/021, the Navarra Regional Government (27/2011, 45/2011, 122/2014), PNSD 2020/2021, and the University of Navarra. LB and AW acknowledge that the COSM and SMC are part of the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research, SIMPLER. SIMPLER receives funding through the Swedish Research Council (grant no 2017–00644). RM acknowledges funding from the Tehran University of Medical Sciences (grant number: 81/15), Cancer Research UK (grant number: C20/A5860), the Intramural Research Program of the U.S. National Cancer Institute, NIH, and the International Agency for Research on Cancer. SMAM and VCL acknowledge that ELSA-Brasil was supported by the Brazilian Ministry of Health (Department of Science and Technology) and Ministry of Science, Technology and Innovation (Financiadora de Estudos e Projetos (FINEP), grant numbers 01 06 0010.00, 01 06 0212.00, 01 06 0300.00, 01 06 0278.00, 01 06 0115.00 and 01 06 0071.00) and the National Council for Scientific and Technological Development (CNPq). JK acknowledges funding from the Korea Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea (4845-301 and 4851-302), and the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C9A6047623). DS and ML acknowledge that this work of MTC was supported by the American Institute for Cancer Research (grant number 05B047) and the Consejo Nacional de Ciencia y Tecnología (CONACyT) (grant number S0008-2009-1: 000000000115312). LLM acknowledges funding from the US National Institutes of Health grant U01 CA164973, SSSM received the Wiebe Visser International Dairy Nutrition Prize and has received recent research funding (2019) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation. PMV and PV acknowledge funding from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468, 33CS30-148401 and 33CS30_177535/1). MK and the Whitehall II study were supported by the UK Medical Research Council (MRCMR/R024227/1), the Wellcome Trust (221854/Z/20/Z) and the US National Institutes of Health (NIH, RF1AG062553, R01AG056477), during the conduct of the study. The funding sources did not participate in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript., We would like to thank the participants, principal investigators, and study teams of the individual cohorts included in this collaboration. The work presented herein was made possible using the OBiBa suite (http://www.obiba.org), a software suite developed by Maelstrom Research (www.maelstrom-research.org), and DataSHIELD (http://www.datashield.ac.uk), a software suite developed by the Data to Knowledge (D2K) Research Group. We thank EPIC-InterAct collaborators and Nicola Kerrison at the MRC Epidemiology Unit for assistance relating to the EPIC-InterAct dataset. We also thank the AusDiab Steering Committee for providing data from the AusDiab study. Moreover, we thank the NIH Biologic Specimen and Data Repository Information Coordinating Center and the ARIC, CARDIA, MESA, PRHHP and WHI OS study for providing data for this study., and HAL UVSQ, Équipe

Bradbury, Charlotte A., Lawler, Patrick R., Stanworth, Simon J., McVerry, Bryan J., McQuilten, Zoe, Higgins, Alisa M., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Berry, Lindsay R., Lorenzi, Elizabeth, Zarychanski, Ryan, Arabi, Yaseen M., Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Bhimani, Zahra, Bihari, Shailesh, Bonten, Marc J. M., Brunkhorst, Frank M., Buzgau, Adrian, Buxton, Meredith, Carrier, Marc, Cheng, Allen C., Cove, Matthew, Detry, Michelle A., Estcourt, Lise J., Fitzgerald, Mark, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Hills, Thomas, Huang, David T., Horvat, Christopher M., Hunt, Beverley J., Ichihara, Nao, Lamontagne, Francois, Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Marshall, John C., McAuley, Daniel F., McGlothlin, Anna, McGuinness, Shay P., Middeldorp, Saskia, Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Neal, Matthew D., Nichol, Alistair D., Parke, Rachael L., Parker, Jane C., Reyes, Luis, Saito, Hiroki, Santos, Marlene S., Saunders, Christina T., Serpa-Neto, Ary, Seymour, Christopher W., Shankar-Hari, Manu, Singh, Vanessa, Tolppa, Timo, Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Derde, Lennie P. G., Webb, Steve A., Gordon, Anthony C., Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Vermassen, Joris, REMAP-CAP Investigators, University of Bristol [Bristol], University Health Network, University of Toronto, University of Oxford, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Monash University [Melbourne], Imperial College London, University of Manitoba [Winnipeg], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Medical Center [Utrecht], St. Michael's Hospital, 215522, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH, U.S. Department of Defense, DOD, National Institute of General Medical Sciences, NIGMS, National Institute of Neurological Disorders and Stroke, NINDS, Gordon and Betty Moore Foundation, GBMF, Medtronic, Baxter International, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Wellcome Trust, WT, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, LAM Therapeutics, Canadian Institutes of Health Research, IRSC: 158584, Medical Research Council, MRC, National Institute for Health and Care Research, NIHR, European Commission, EC, National Heart and Lung Institute, NHLI, Queen's University Belfast, QUB: US8962032, National Health and Medical Research Council, NHMRC: APP1101719, National Medical Research Council, NMRC, Health Research Council of New Zealand, HRC: 16/631, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Swedish Orphan Biovitrum, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support: This study was funded by the following: the Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) consortium of the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Rapid European COVID-19 Emergency Research Response (RECOVER) consortium of the European Union’s Horizon 2020 Research and Innovation Programme (grant 101003589), the Australian National Health and Medical Research Council (grant APP1101719), the Health Research Council of New Zealand (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the University of Pittsburgh Medical Center (UPMC) Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (grant PHRC-20-0147), the Minderoo Foundation, and the Wellcome Trust Innovations Project (grant 215522). Dr Shankar-Hari is funded by an NIHR clinician scientist fellowship (grant CS-2016-16-011) and Dr Gordon is funded by an NIHR research professorship (grant RP-2015-06-18)., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Clinical Trials Group, the Irish Critical Care Clinical Trials Network, the UK Critical Care Research Group and the International Forum of Acute Care Trialists., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands, reported receipt of personal fees from Lilly, BMS-Pfizer, Bayer, Amgen, Novartis, Janssen, Portola, Ablynx, and Grifols. Dr Lawler reported receipt of personal fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and royalties from McGraw-Hill Publishing. Dr McVerry reported receipt of grants from the National Heart, Lung, and Blood Institute and Bayer Pharmaceuticals and personal fees from Boehringer Ingelheim. Dr L. Berry reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Lorenzi reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Zarychanski reported receipt of grants from the Canadian Institutes of Health Research, LifeArc, Research Manitoba, the CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, and the Thistledown Foundation and research operating support as the Lyonel G. Israels Research Chair in Hematology. Dr Bonten reported membership in international study steering committees, advisory boards, and independent data safety and monitoring committees funded by Janssen Vaccines, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Sanofi Pasteur (all reimbursements to UMC Utrecht). Dr Brunkhorst reported receipt of grants from Jena University Hospital. Dr Buxton reported receipt of a gift from the Breast Cancer Research Foundation and contracts with Amgen and Eisai. Dr Carrier reported receipt of grants from BMS-Pfizer and personal fees from Bayer, Sanofi, Servier, Leo Phama, and BMS-Pfizer to his institution. Dr Cove reported receipt of grants from the National Medical Research Council and personal fees from Baxter and Medtronic. Dr Estcourt reported receipt of grants from the UK National Institute for Health Research (NIHR) and the European Union Horizon 2020 Research and Innovation Programme. Dr Haniffa reported receipt of grants from the UK Research and Innovation/Medical Research Council African Critical Care Registry Network. Dr Horvat reported receipt of grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Dr Ichihara reported being affiliated with the Department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration supported by the National Clinical Database, Johnson & Johnson, and Nipro Corporation. Dr Marshall reported receipt of personal fees from AM Pharma and Critical Care Medicine. Dr McAuley reported receipt of personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Lilly, Vir Biotechnology, Faron Pharmaceutical, and SOBI and grants from the NIHR, the Wellcome Trust, Innovate UK, the UK Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, in addition, Dr McAuley had a Queen’s University Belfast patent for novel treatment for inflammatory disease (US8962032), was co-director of research at the Intensive Care Society until June 2021, and was director of the Efficacy and Mechanisms Evaluation Program for the UK Medical Research Council/NIHR. Dr Middeldorp reported receipt of personal fees from Daiichi Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Portola/Alexion, AbbVie, BMS-Pfizer, Sanofi, and Viatris, all paid to his institution, and grants from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim. Dr Neal reported equity in Haima Therapeutics, receipt of personal fees from Janssen Pharma and Haemonetics, and receipt of grants from Instrumentation Laboratory, the National Institutes of Health, and the Department of Defense. Dr Nichol reported receipt of personal fees from AM Pharma, paid to his university, and grants from Baxter. Dr Parke reported receipt of grants from Fisher and Paykel Healthcare NZ. Dr Serpa-Neto reported receipt of personal fees from Drager and Endpoint Health. Dr Seymour reported receipt of grants from the Gordon and Betty Moore Foundation and the National Institutes of Health/National Institute of General Medical Sciences. Dr Lewis reported being senior medical scientist at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr S. Berry reported being an employee with an ownership role at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Derde reported being a coordinating committee member for the European Clinical Research Alliance on Infectious Diseases, a member of the Dutch Intensivists Task Force on Acute Infectious Threats, a member of the International Scientific Advisory Board for Sepsis Canada, and a member of the Dutch Academy of Sciences’ Pandemic Preparedness Plan committee. Dr Gordon reported receipt of personal fees from 30 Respiratory, paid to his institution. No other disclosures were reported., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Investigators, REMAP-CAP Writing Committee for the REMAP-CAP, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Intensive Care Medicine

Stanislas Grassin-Delyle, Michaela Semeraro, Elodie Lamy, Saïk Urien, Iléana Runge, Frantz Foissac, Naim Bouazza, Jean-Marc Treluyer, Monica Arribas, Ian Roberts, Haleema Shakur-Still, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité de recherche clinique / Centre d'investigation clinique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), London School of Hygiene and Tropical Medicine (LSHTM), Bill and Melinda Gates Foundation, BMGF: OPP1176150, Wellcome Trust, WT: 208870, Wellcome Trust (208870), Bill & Melinda Gates Foundation (OPP1176150)., and HAL UVSQ, Équipe

Gabriela P. Peralta, Raquel Granell, Annabelle Bédard, Anne‐Elie Carsin, Elaine Fuertes, Laura D. Howe, Sandra Márquez, Deborah L. Jarvis, Judith Garcia‐Aymerich, CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Universität Zürich [Zürich] = University of Zurich (UZH), University of Bristol [Bristol], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hospital del Mar Medical Research Institute [Barcelona, Spain] (IMIM), Imperial College London, Wellcome Trust, WT, Medical Research Council, MRC: 076467/Z/05/Z, G0401540/73080, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, MICINN, Horizon 2020: 633212, The present analyses are part of the Aging Lungs in European Cohorts (ALEC) Study ( www.alecstudy.org ), which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 633212. The content of this article reflects only the authors' views, and the European Commission is not liable for any use that may be made of the information contained therein. The UK Medical Research Council and Wellcome (Grant reference: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Laura Howe and Raquel Granell will serve as guarantors for the contents of this paper. A comprehensive list of grant funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). Specifically, grants from Wellcome Trust and MRC (076467/Z/05/Z and G0401540/73080) supported the collection of body composition and lung function data at 15 years. We acknowledge support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018‐000806‐S), and support from the Generalitat de Catalunya through the CERCA Program., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), HAL UVSQ, Équipe, and Aging Lungs in European Cohorts - ALEC - - H20202015-05-01 - 2019-04-30 - 633212 - VALID

Manuela M. Bergmann, Tammy Y.N. Tong, Anna Stubbendorff, Elisabeth H. M. Temme, Claudia Agnoli, Ulrika Ericson, Antonio Agudo, Mélanie Deschasaux, Elisabete Weiderpass, Konstantinos K. Tsilidis, Dagfinn Aune, Guri Skeie, Giovanna Masala, Torkjel M. Sandanger, Emmanuelle Kesse-Guyot, Gianluca Severi, Charlotta Rylander, Francesca Mancini, Miguel A. Rodríguez Barranco, Marie-Christine Boutron-Ruault, Paolo Vineis, Mathilde Touvier, Pietro Ferrari, Marc J. Gunter, Daniel B Ibsen, Jolanda M. A. Boer, María José Pérez, Inge Huybrechts, Matthias B. Schulze, Anika Knuppel, Keren Papier, Elio Riboli, Bernard Srour, Christina C. Dahm, Jessica E. Laine, Tilmann Kühn, Medical Research Council (MRC), Imperial College London, University of Bern, Centre international de Recherche sur le Cancer (CIRC), Bjørknes University College [Oslo, Norvège], Oslo University Hospital [Oslo], University of Potsdam, German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), National Institute for Public Health and the Environment [Bilthoven] (RIVM), IRCCS Istituto Nazionale dei Tumori [Milano], Lund University [Lund], Aarhus University [Aarhus], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Espace régional de réflexion éthique de Normandie (EREN), Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), ibs.GRANADA Instituto de Investigación Biosanitaria [Granada, Spain], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Granada [Granada], University of Oxford [Oxford], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), The Arctic University of Norway (UiT), Italian Institute of Technology (IIT), International Arctic Research Center, University of Alaska, Fairbanks, IARC, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Wellcome Trust, WT: 205212/Z/16/Z, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, MR/M501669/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, The coordination of EPIC is financially supported by IARC and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre. The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, INSERM (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Statistics Netherlands (The Netherlands), Health Research Fund - Instituto de Salud Carlos III, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (MRC, 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford, UK). JEL was supported by an MRC Early Career Fellowship (MR/M501669/1). We acknowledge the Netherlands Cancer Registry and Statistics Netherlands (The Netherlands) for contributions to data acquisition. KP and AK are supported by the Wellcome Trust (Livestock, Environment and People, LEAP, grant number 205212/Z/16/Z). We acknowledge Corinne Casagrande and Genevieve Nicolas who assisted in the matching of the dietary intake data with the Greenhouse Gas and Landuse data. We also acknowledge Bertrand Hemon for database compilation and Carine Biessy for her contribution to the sensitivity analyses. Where authors are identified as personnel of the IARC or WHO, the authors alone are responsible for the views expressed in this Article and they do not necessarily represent the decisions, policy, or views of the IARC or WHO., Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, INSERM (France), Health Research Fund - Instituto de Salud Carlos III, Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), University of Potsdam = Universität Potsdam, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Universidad de Granada = University of Granada (UGR), Nuffield Department of Population Health [Oxford], University of Oxford, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli Studi di Firenze = University of Florence (UniFI), Institut Gustave Roussy (IGR), The Arctic University of Norway [Tromsø, Norway] (UiT), European Commission (DG-SANCO), the International Agency for Research on Cancer (IARC), MRC Early Career Fellowship (MR/M501669/1), and HAL UVSQ, Équipe

Dorling, L., Carvalho, S., Allen, J., Parsons, M.T., Fortuno, C., Gonzalez-Neira, A., Heijl, S.M., Adank, M.A., Ahearn, T.U., Andrulis, I.L., Auvinen, P., Becher, H., Beckmann, M.W., Behrens, S., Bermisheva, M., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bremer, M., Briceno, I., Camp, N.J., Campbell, A., Castelao, J.E., Chang-Claude, J., Chanock, S.J., Chenevix-Trench, G., Collee, J.M., Czene, K., Dennis, J., Dork, T., Eriksson, M., Evans, D.G., Fasching, P.A., Figueroa, J., Flyger, H., Gabrielson, M., Gago-Dominguez, M., Garcia-Closas, M., Giles, G.G., Glendon, G., Guenel, P., Gundert, M., Hadjisavvas, A., Hahnen, E., Hall, P., Hamann, U., Harkness, E.F., Hartman, M., Hogervorst, F.B.L., Hollestelle, A., Hoppe, R., Howell, A., Jakubowska, A., Jung, A., Khusnutdinova, E., Kim, S.W., Ko, Y.D., Kristensen, V.N., Lakeman, I.M.M., Li, J.M., Lindblom, A., Loizidou, M.A., Lophatananon, A., Lubinski, J., Luccarini, C., Madsen, M.J., Mannermaa, A., Manoochehri, M., Margolin, S., Mavroudis, D., Milne, R.L., Taib, N.A.M., Muir, K., Nevanlinna, H., Newman, W.G., Oosterwijk, J.C., Park, S.K., Peterlongo, P., Radice, P., Saloustros, E., Sawyer, E.J., Schmutzler, R.K., Shah, M.T., Sim, X., Southey, M.C., Surowy, H., Suvanto, M., Tomlinson, I., Torres, D., Truong, T., Asperen, C.J. van, Waltes, R., Wang, Q., Yang, X.H.R., Pharoah, P.D.P., Schmidt, M.K., Benitez, J., Vroling, B., Dunning, A.M., Teo, S.H., Kvist, A., Hoya, M. de la, Devilee, P., Spurdle, A.B., Vreeswijk, M.P.G., Easton, D.F., NBCS Collaborators, KConFab Investigators, SGBCC Investigators, Clinical Genetics, Medical Oncology, Apollo - University of Cambridge Repository, Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), University of Helsinki, Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Wellcome Trust, WT: 633784, v203477/Z/16/Z, Horizon 2020 Framework Programme, H2020, Cancer Research UK, CRUK: C1287/A16563, The sequencing and analysis for this project was funded by the European Union’s Horizon 2020 Research and Innovation Programme (BRIDGES: grant number 634935) and the Wellcome Trust [grant no: v203477/Z/16/Z]. BCAC co-ordination was additionally funded by the European Union’s Horizon 2020 Research and Innovation Programme (BRIDGES: grant number 634935, BCAST: grant number 633784) and by Cancer Research UK [C1287/A16563]. Study specific funding is given in the Additional Note., and HAL UVSQ, Équipe

Amélie Keller, Jonathan Groot, Joane Matta, Feifei Bu, Tarik El Aarbaoui, Maria Melchior, Daisy Fancourt, Marie Zins, Marcel Goldberg, Anne-Marie Nybo Andersen, Naja H. Rod, Katrine Strandberg-Larsen, Tibor V. Varga, University of Copenhagen = Københavns Universitet (UCPH), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University College of London [London] (UCL), PRJ-2019-00020, 09‐067124, March of Dimes Foundation, MDF, AstraZeneca, Sundhed og Sygdom, Det Frie Forskningsråd, FSS, DFF: 271‐08‐0839/06‐066023, SSVF 0646, Natur og Univers, Det Frie Forskningsråd, FNU, DFF: DFF—4183‐00152, DFF—4183‐00594, Velux Fonden: 36336, Pfizer Foundation, Merck Sharp and Dohme, MSD, Wellcome Trust, WT: 205407/Z/16/Z, 221400/Z/20/Z, UK Research and Innovation, UKRI: ES/S002588/1, National Health Insurance Administration, NHI, Nuffield Foundation: WEL/FR-000022583, Health Foundation, Cardiff University, Swansea University, Agence Nationale de la Recherche, ANR: -10-COHO-06, -20-COVI-000, ANR-11-INBS-0002, Institut National de la Santé et de la Recherche Médicale, Inserm: 20-26, Københavns Universitet, KU, Fondation pour la Recherche Médicale, FRM: 20RR052-00, Lundbeckfonden: R100‐A9193, Nordea-fonden: 02‐2013‐2014, AU R9‐A959‐13‐S804, Institut National Du Cancer, INCa, Egmont Fonden, H. Lundbeck A/S, This study was made possible by a grant from the RealDania Foundation (PRJ-2019-00020 ‘Indoor environment and child health…’). The DNBC was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation and other minor grants. 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), the Lundbeck Foundation (195/04, R100‐A9193), The Innovation Fund Denmark 0603‐00294B (09‐067124), the Nordea Foundation (02‐2013‐2014), Aarhus Ideas (AU R9‐A959‐13‐S804), a University of Copenhagen Strategic Grant (IFSV 2012) and the Danish Council for Independent Research (DFF—4183‐00594 and DFF—4183‐00152). Follow-up of mother and children in the COVID-19 data collection was supported by a grant from the Velux Foundation (grant number 36336, ‘Standing together at a distance—How Danes are living with the Corona Crisis’). The TEMPO cohort received funding from the French National Research Agency (ANR) including the Flash COVID-19 funding scheme, the French Institute for Public Health Research-IReSP (TGIR Cohortes), the French Inter-departmental Mission for the Fight against Drugs and Drug Addiction (MILDeCA), the French Institute of Cancer (INCa), and the Pfizer Foundation. The CONSTANCES COVID-19 Study was funded by: ANR (Agence Nationale de la Recherche, #ANR-20-COVI-000, #ANR-10-COHO-06), Fondation pour la Recherche Médicale (#20RR052-00), Inserm (Institut National de la Santé et de la Recherche Médicale, #C20-26). The CONSTANCES Cohort Study was supported and funded by the French National Health Insurance Fund ('Caisse nationale d’assurance maladie', CNAM). The CONSTANCES Cohort Study is an 'Infrastructure nationale en Biologie et Santé' and benefits from a grant from the French National Agency for Research (ANR-11-INBS-0002). CONSTANCES is also partly funded by Merck Sharp & Dohme (MSD), AstraZeneca, Lundbeck and L’Oréal. None of these funding sources had any role in the design of the study, collection and analysis of data or decision to publish. The Covid-19 Social Study was funded by the Nuffield Foundation [WEL/FR-000022583], but the views expressed are those of the authors and not necessarily the Foundation. The study was also supported by the MARCH Mental Health Network funded by the Cross-Disciplinary Mental Health Network Plus initiative supported by UK Research and Innovation [ES/S002588/1], and by the Wellcome Trust [221400/Z/20/Z]. DF was funded by the Wellcome Trust [205407/Z/16/Z]. The researchers are grateful for the support of a number of organisations with their recruitment efforts including: the UKRI Mental Health Networks, Find Out Now, UCL BioResource, SEO Works, FieldworkHub, and Optimal Workshop. The study was also supported by HealthWise Wales, the Health and Care Research Wales initiative, which is led by Cardiff University in collaboration with SAIL, Swansea University. The funders had no role in the study design, data collection, data analysis, interpretation, the writing of the report, and decisions on where to publish., The authors thank the INSERM-Versailles Saint Quentin en Yvelines University ?Population-based Epidemiologic Cohorts Unit? (Cohortes ?pid?miologiques en population) which designed and manages the Constances Cohort Study. They also thank the National Health Insurance Fund (?Caisse nationale d?assurance maladie des travailleurs salaries,? CNAMTS) and its Health Screening Centres (?Centres d?examens de sant??), which are collecting a large part of the data, as well as the National Old-Age Insurance Fund (Caisse nationale d?assurance vieillesse) for its contribution to the constitution of the cohort, ClinSearch, Asqualab and Eurocell, which are conducting the data quality control., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), ANR-11-INBS-0002,CONSTANCES,La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance(2011), HAL UVSQ, Équipe, Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID, and Infrastructures - La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance - - CONSTANCES2011 - ANR-11-INBS-0002 - INBS - VALID

Pietro Ferrari, Fulvio Ricceri, Christina C. Dahm, Kim Overvad, Sabina Sieri, Elisabete Weiderpass, Eleni Peppa, María José Sánchez, Leila Luján Barroso, Marta Solans Margalef, Matthias B. Schulze, Federico Canzian, Giovanna Masala, Florentin Spaeth, Dagfinn Aune, Roel Vermeulen, Tilman Kühn, Delphine Casabonne, Karin Jirstom, Anna Karakatsani, José María Huerta, Yahya Mahamat-Saleh, Paul Brennan, Cecilie Kyrø, Mats Jerkeman, Caroline Besson, Pilar Amiano Exezarreta, Virginia Menéndez, Elio Riboli, Julie A. Schmidt, Rosario Tumino, Sairah L.F. Chen, Marc J. Gunter, Eva Ardanaz, Antonia Trichopoulou, Alexandra Nieters, Marie-Christine Boutron-Ruault, Anne Tjønneland, Fatemeh Saberi Hosnijeh, Sabine Naudin, Salvatore Panico, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre Hospitalier de Versailles André Mignot (CHV), Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Food Standards Agency, FSA Cancer Research UK, CRUK: C864/A14136, C8221/A19170, C570/A16491 RD06/0020 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Université Claude Bernard Lyon 1, UCBL Wellcome Trust, WT Ligue Contre le Cancer 6236 German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Department of Health, Australian Government Ministry of Health and Social Solidarity, Greece Kræftens Bekæmpelse, DCS British Heart Foundation, BHF Instituto de Salud Carlos III, ISCIII National Research Council, NRC Mutuelle Générale de l'Education Nationale, MGEN Hellenic Health Foundation, HHF Stroke Association Institut National de la Santé et de la Recherche Médicale, Inserm Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, IARC Deutsche Krebshilfe Cancerfonden World Cancer Research Fund, WCRF Stavros Niarchos Foundation, SNF Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Medical Research Council, MRC: MR/M012190/1, MR/N003284/1, MC‐UU_12015/1, We thank Carine Biessy and Bertrand Hemon for their technical support and contribution to this work. We are also grateful to all the EPIC participants who have been part of the project and to the many other members of the study teams who have enabled this research. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Health Research Fund, Regional Governments of Andalucýa, Asturias, Basque Country, Murcia (project 6236) and Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa (RD06/0020, Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). This work was part of Sabine Naudin's PhD at Claude Bernard Lyon I University (France), funded by Région Auvergne Rhône‐Alpes, ADR 2016 (France).

Vincent Le Moigne, Daniela Rodriguez Rincon, Simon Glatigny, Christian M. Dupont, Christelle Langevin, Amel Ait Ali Said, Stephen A. Renshaw, R. Andres Floto, Jean-Louis Herrmann, Audrey Bernut, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Cambridge [UK] (CAM), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateforme d'Infectiologie Expérimentale des Rongeurs et Poissons (IERP (UE 0907)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Sheffield [Sheffield], Hôpital Raymond Poincaré [AP-HP], 160161, SRC018, G0700091, GR077544AIA, SRC002, 751977, H2020-MSCA-IF-2016, ARF201909009156, Wellcome Trust, WT: 107032AIA, MR/M004864/1, Medical Research Council, MRC: MRNO2995X/1, These authors contributed equally to this work. ‡These authors contributed equally to this work. §Present address: Laboratory of Pathogen Host Interactions, CNRS/UM, University of Montpellier, UMR 5235, Montpellier, France. Supported by the European Community’s Horizon 2020-Research and Innovation Framework Program (H2020-MSCA-IF-2016) under the Marie Curie Individual Fellowship CFZEBRA (751977) and by the Fondation pour la Recherche Médicale -Espoirs de la Recherche-Program (ARF201909009156) to A.B., a United Kingdom Cystic Fibrosis (CF) Trust Strategic Research Centre award (SRC002) and the Wellcome Trust (107032AIA) to R.A.F. and D.R.R., a Medical Research Council Programme grant (MR/M004864/1) to S.A.R., and and United Kingdom CF Trust workshop funding (160161) and a United Kingdom CF Trust Strategic Research Centre award (SRC018) to A.B., S.A.R., and R.A.F. This work was supported by antimicrobial resistance cross-council funding from the Medical Research Council to the SHIELD consortium (MRNO2995X/1) to A.B. and S.A.R. The authors thank the CYMAGES and the Wolfson Light Microscopy (Medical Research Council grant G0700091) and Wellcome Trust (grant GR077544AIA) facilities.

Lozano, Manuel, Yousefi, Paul, Broberg, Karin, Soler-Blasco, Raquel, Miyashita, Chihiro, Pesce, Giancarlo, Kim, Woo Jin, Rahman, Mohammad, Bakulski, Kelly, Haug, Line, Ikeda-Araki, Atsuko, Huel, Guy, Park, Jaehyun, Relton, Caroline, Vrijheid, Martine, Rifas-Shiman, Sheryl, Oken, Emily, Dou, John, Kishi, Reiko, Gutzkow, Kristine, Annesi-Maesano, Isabella, Won, Sungho, Hivert, Marie-France, Fallin, M. Daniele, Vafeiadi, Marina, Ballester, Ferran, Bustamante, Mariona, Llop, Sabrina, Universitat de València (UV), University of Bristol [Bristol], Karolinska Institutet [Stockholm], Lund University [Lund], Hokkaido Information University, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kangwon National University, Harvard Medical School [Boston] (HMS), University of Michigan [Dearborn], University of Michigan System, Norwegian Institute of Public Health [Oslo] (NIPH), Seoul National University [Seoul] (SNU), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Spanish Consortium for Research on Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Johns Hopkins University (JHU), University of Crete [Heraklion] (UOC), 1999SGR 00241, 15/0025, 17/00260, 20/0006, FIS-FEDER PI16/1288, FIS-FEDER PI19/1338, FIS-FEDER-PI03–1615, FIS-FEDER-PI06/0867, FIS-PI04/1436, FIS-PI08/1151, FIS-PI11/00610, MC_UU_00011/5, National Institutes of Health, NIH: R37 HD034568, National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK: R01 DK10324, National Institute of Neurological Disorders and Stroke, NINDS: 06A1, 1 UO1 NS 047537–01, National Institute of Environmental Health Sciences, NIEHS: N01-ES-75558, Z01-ES-49019, Centre International de Recherche sur le Cancer, CIRC, Japan Agency for Medical Research and Development, AMED: JPMH18950314, JPMH19188595, Wellcome Trust, WT: 102215/2/13/2, Horizon 2020 Framework Programme, H2020: 874583, Medical Research Council, MRC: MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8, WT088806, Biotechnology and Biological Sciences Research Council, BBSRC: BB/I025263/1, BB/I025751/1, European Commission, EC: 261357, European Research Council, ERC: 268479, University of Bristol, Japan Society for the Promotion of Science, KAKEN, Ministry of Education, Culture, Sports, Science and Technology, Monbusho: JP15H04780, JP16H02645, JP18H03035, JP18K10022, JP18K10042, JP19H01071, JP19K10576, JP19K10636, JP19K20457, JP19K22730, JPMEERF20145054, JPMEERF20175053, JPMEERF20205002, Bundesministerium für Bildung und Forschung, BMBF, Generalitat Valenciana, GVA: 090,430, BEST/2020/059, Ministry of Health, Labour and Welfare, MHLW: JPMH14427175, JPMH17932352, JPMH19189425, Helse- og Omsorgsdepartementet, Ministry of Environment, MOE: 2017001360005, Korea Environmental Industry and Technology Institute, KEITI, Instituto de Salud Carlos III, ISCIII: CB06/02/0041, INMA G03/176, Ministerio de Ciencia e Innovación, MICINN: MTM2015-68140-R, Seventh Framework Programme, FP7: R01HL111108, R01NR013945, Norges Forskningsråd: 221097, Institut National Du Cancer, INCa, Horizon 2020: 733206, Ministry of Internal Affairs and Communications, MIC: JPMI10001, Consejería de Educación e Investigación, The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research , NIH/NIEHS (contract no N01-ES-75558 ), NIH/NINDS (grant no. 1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1 ). MoBa1 and MoBa 2 are supported by the Intramural Research Program of the NIH , National Institute of Environmental Health Sciences ( Z01-ES-49019 ) and Norwegian Research Council /BIOBANK (grant no 221097 ). The work in MoBa3 was supported in part by a Postdoctoral Fellowship grant from the Ulleval Hospitals Research Council (now under Oslo University Hospital) and travel grants from the Unger-Vetlesens foundation and the Norwegian American Womens Club , all to M.C.M.K. MoBa3 epigenomics data analyses were funded by INCA/Plan Cancer-EVA-INSERM, France, and the International Childhood Cancer Cohort Consortium (I4C), and performed by the Epigenetics Group at the International Agency for Research on Cancer (IARC, Lyon, France), A.G. was supported by the grant from INCA /Plan Cancer-EVA-INSERM (France, 2015) to Z.H. and also by the IARC Postdoctoral Fellowship, partially supported by the EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND)., ALSPAC study was funded by the UK Medical Research Council and the Wellcome Trust (grant ref: 102215/2/13/2 ) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, PY and CR, who will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). The Accessible Resource for Integrated Epigenomics Studies (ARIES), was funded by the UK Biotechnology and Biological Sciences Research Council ( BB/I025751/1 and BB/I025263/1 ). Additional epigenetic profiling of ALSPAC was supported by the UK Medical Research Council (MRC) Integrative Epidemiology Unit and the University of Bristol ( MC_UU_12013_1 , MC_UU_12013_2 , MC_UU_12013_5 and MC_UU_12013_8 ), the Wellcome Trust ( WT088806 ) and the United States National Institute of Diabetes and Digestive and Kidney Diseases ( R01 DK10324 ). PY and CR are supported by the UK MRC Integrative Epidemiology Unit ( MC_UU_00011/5 )., The Project Viva cohort is funded by NIH grants R01HL111108 , R01NR013945 , and R37 HD034568 ., The Hokkaido-Sapporo Study is supported by Grant-in-Aid for Scientific Research from the Japanese Ministry of Health , Labour and Welfare ( JPMH14427175 , JPMH19189425 , JPMH17932352 ), the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology ( JP16H02645 , JP19H01071 , JP18H03035 , JP15H04780 , JP19K10576 , JP19K10636 , JP18K10042 , JP18K10022 , JP19K22730 , JP19K20457 ), and an Environment Research and Technology Development fund ( JPMEERF20145054 , JPMEERF20175053 , JPMEERF20205002 ), AMED ( JPMH19188595 , JPMH18950314 ), and Ministry of Internal Affairs and Communications ( JPMI10001 )., Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III ( Red INMA G03/176 , CB06/02/0041 ), Spanish Ministry of Health ( FIS-PI04/1436 , FIS-PI08/1151 including FEDER funds, FIS-PI11/00610 , FIS-FEDER-PI06/0867 , FIS-FEDER-PI03–1615 , FIS-FEDER PI16/1288 , FIS-FEDER PI19/1338, Miguel Servet FEDER 15/0025 and 20/0006, FIS-FSE : 17/00260 ), Generalitat de Catalunya-CIRIT 1999SGR 00241 , Generalitat Valenciana BEST/2020/059 , Fundacio ́ La Marato ́ de TV3 ( 090,430 ), EU Commission ( 261357 -MeDALL: Mechanisms of the Development of ALLergy), and European Research Council ( 268479 -BREATHE: Brain dEvelopment and Air polluTion ultrafine particles in school childrEn)., The authors would also like to thank Ingvild Essen for thorough field work, Heidi Marie Nordheim for biological sample management and the MoBa administrative unit (MoBa). The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research . We are grateful to all the participating families in Norway who take part in this on-going cohort study., The Rhea project was financially supported by European projects , and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014, ‘Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). The work was also supported by MICINN ( MTM2015-68140-R ), Centro Nacional de Genotipado - CEGEN-PRB2-ISCIII, the H2020 -EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583 ) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206 ) (Early Life stressors and Lifecycle Health (LIFECYCLE))., This study was supported by the Korean Environment Industry & Technology Institute ( KEITI ) through 'the Environmental Health Action Program', funded by Korea Ministry of Environment ( 2017001360005 )., ALSPAC. ALSPAC study is extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. We would like to acknowledge Oliver Lyttleton, Hashem Shihab, Nabila Kazmi and Geoff Woodward for their earlier contribution to the generation of ARIES data (ALSPAC methylation data). INMA, The authors would like to thank all the participants for their generous collaboration. full roster of the INMA project investigators can be found at http://www.proyectoinma.org/presentacion-inma/listado-investigadores/en_listado-investigadores.html. MoBa, The authors would also like to thank Ingvild Essen for thorough field work, Heidi Marie Nordheim for biological sample management and the MoBa administrative unit (MoBa). The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. Project Viva, Project Viva researchers would like to thank all mothers, children and families for their ongoing participation. RHEA, The authors would like to thank Georgia Chalkiadaki and Danai Feida for biological sample management, to Eirini Michalaki, Mariza Kampouri, Anny Kyriklaki and Minas Iakovidis for field study performance and to Maria Fasoulaki for administrative assistance. SAPPORO-HOKKAIDO, We would like to express our appreciation to all of the study participants of the Hokkaido Study on Environment and Children? Health. We also express our profound gratitude to all personnel in the hospitals and clinics that collaborated with the study, including Sapporo Toho Hospital, Keiai Hospital, Endo Kikyo Maternity Clinic, Shiroishi Hospital, Memuro Municipal Hospital, Aoba Ladies Clinic, Obihiro-Kyokai Hospital, Akiyama Memorial Hospital, Sapporo Medical University Hospital, Hokkaido University Hospital, Kitami Red Cross Hospital, Hoyukai Sapporo Hospital, Gorinbashi Hospital, Hashimoto Clinic, Asahikawa Medical College Hospital, Hakodate Central General Hospital, Ohji General Hospital, Nakashibetsu Municipal Hospital, Sapporo Tokushukai Hospital, Asahikawa Red Cross Hospital, Wakkanai City Hospital, Kushiro Rosai Hospital, Sapporo-Kosei General Hospital, Shibetsu City General Hospital, Nikko Memorial Hospital, Sapporo City General Hospital, Kohnan Hospital, Hakodate City Hospital, Hokkaido Monbetsu Hospital, Tenshi Hospital, Hakodate Goryoukaku Hospital, Nakamura Hospital, Kin-ikyo Sapporo Hospital, Kitami Lady's Clinic, Engaru-Kosei General Hospital, Kushiro Red Cross Hospital, Nayoro City General Hospital, and Obihiro-Kosei General Hospital. We also deeply express our gratitude to the staff of The Hokkaido Study on Environment and Children's Health for their considerable efforts to support our study, including N. Goto, O. Hayashi, T. Hikichi, N. Kanda, K. Kunita, K. Miura, Y. Shibasaki, K. Sugawara, K. Tanaka, E. Toyama, and T. Yoshikawa. Special thanks to Ms. Mimi Takahashi on her effort to support writing this manuscript.ALSPAC study was funded by the UK Medical Research Council and the Wellcome Trust (grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, PY and CR, who will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The Accessible Resource for Integrated Epigenomics Studies (ARIES), was funded by the UK Biotechnology and Biological Sciences Research Council (BB/I025751/1 and BB/I025263/1). Additional epigenetic profiling of ALSPAC was supported by the UK Medical Research Council (MRC) Integrative Epidemiology Unit and the University of Bristol (MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5 and MC_UU_12013_8), the Wellcome Trust (WT088806) and the United States National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK10324). PY and CR are supported by the UK MRC Integrative Epidemiology Unit (MC_UU_00011/5).Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03?1615, FIS-FEDER PI16/1288, FIS-FEDER PI19/1338, FIS-FSE: 17/00260), Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat Valenciana BEST/2020/059, Fundacio ? La Marato ? de TV3 (090,430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: Brain dEvelopment and Air polluTion ultrafine particles in school childrEn).This study was supported by the Korean Environment Industry & Technology Institute (KEITI) through ?the Environmental Health Action Program?, funded by Korea Ministry of Environment (2017001360005).The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537?01 and grant no.2 UO1 NS 047537?06A1). MoBa1 and MoBa 2 are supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and Norwegian Research Council/BIOBANK (grant no 221097). The work in MoBa3 was supported in part by a Postdoctoral Fellowship grant from the Ulleval Hospitals Research Council (now under Oslo University Hospital) and travel grants from the Unger-Vetlesens foundation and the Norwegian American Womens Club, all to M.C.M.K. MoBa3 epigenomics data analyses were funded by INCA/Plan Cancer-EVA-INSERM, France, and the International Childhood Cancer Cohort Consortium (I4C), and performed by the Epigenetics Group at the International Agency for Research on Cancer (IARC, Lyon, France), A.G. was supported by the grant from INCA/Plan Cancer-EVA-INSERM (France, 2015) to Z.H. and also by the IARC Postdoctoral Fellowship, partially supported by the EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND).The Project Viva cohort is funded by NIH grants R01HL111108, R01NR013945, and R37 HD034568.The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011?2014, Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012?2015). The work was also supported by MICINN (MTM2015-68140-R), Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII, the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)).The Hokkaido-Sapporo Study is supported by Grant-in-Aid for Scientific Research from the Japanese Ministry of Health, Labour and Welfare (JPMH14427175, JPMH19189425, JPMH17932352), the Ministry of Education, Culture, Sports, Science and Technology (JP16H02645, JP19H01071, JP18H03035, JP15H04780, JP19K10576, JP19K10636, JP18K10042, JP18K10022, JP19K22730, JP19K20457), and an Environment Research and Technology Development fund (JPMEERF20145054, JPMEERF20175053, JPMEERF20205002), AMED (JPMH19188595, JPMH18950314), and Ministry of Internal Affairs and Communications (JPMI10001)., European Project: 261357,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MEDALL(2010), HAL UVSQ, Équipe, and Mechanisms of the Development of ALLergy - MEDALL - - EC:FP7:HEALTH2010-12-01 - 2015-05-31 - 261357 - VALID

Stanislas Grassin-Delyle, Elodie Lamy, Michaela Semeraro, Iléana Runge, Jean-Marc Treluyer, Raoul Mansukhani, Monica Arribas, Ian Roberts, Haleema Shakur-Still, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Bill and Melinda Gates Foundation, BMGF: OPP1176150, Wellcome Trust, WT: 208870, This work was supported by the Wellcome Trust (208870) and the Bill & Melinda Gates Foundation (OPP1176150)., Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de recherche clinique / Centre d'investigation clinique [CHU Necker], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Writing Committee for the REMAP-CAP Investigators, Estcourt, Lise J, Turgeon, Alexis F, McQuilten, Zoe K, McVerry, Bryan J, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Arnold, Donald M, Beane, Abigail, Bégin, Philippe, van Bentum-Puijk, Wilma, Berry, Lindsay R, Bhimani, Zahra, Birchall, Janet E, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Callum, Jeannie L, Chassé, Michaël, Cheng, Allen C, Cove, Matthew E, Daly, James, Derde, Lennie, Detry, Michelle A, De Jong, Menno, Evans, Amy, Fergusson, Dean A, Fish, Matthew, Fitzgerald, Mark, Foley, Claire, Goossens, Herman, Gordon, Anthony C, Gosbell, Iain B, Green, Cameron, Haniffa, Rashan, Harvala, Heli, Higgins, Alisa M, Hills, Thomas E, Hoad, Veronica C, Horvat, Christopher, Huang, David T, Hudson, Cara L, Ichihara, Nao, Laing, Emma, Lamikanra, Abigail A, Lamontagne, François, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, MacLennan, Sheila, Marshall, John, McAuley, Daniel F, McDyer, John F, McGlothlin, Anna, McGuinness, Shay, Miflin, Gail, Montgomery, Stephanie, Mouncey, Paul R, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane C, Priddee, Nicole, Purcell, Damian FJ, Reyes, Luis F, Richardson, Peter, Robitaille, Nancy, Rowan, Kathryn M, Rynne, Jennifer, Saito, Hiroki, Santos, Marlene, Saunders, Christina T, Serpa Neto, Ary, Seymour, Christopher W, Silversides, Jon A, Tinmouth, Alan A, Triulzi, Darrell J, Turner, Anne M, van de Veerdonk, Frank, Walsh, Timothy S, Wood, Erica M, Berry, Scott, Lewis, Roger J, Menon, David K, McArthur, Colin, Zarychanski, Ryan, Angus, Derek C, Webb, Steve A, Roberts, David J, Shankar-Hari, Manu, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Investigators, Writing Committee for the REMAP-CAP, Writing Comm REMAP-CAP Investigators, Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institutes of Health, NIH, National Institute of Child Health and Human Development, NICHD, Pittsburgh Foundation, Breast Cancer Research Foundation, BCRF, Bristol-Myers Squibb, BMS, GlaxoSmithKline, GSK, Medtronic, Baxter International, Manitoba Medical Service Foundation, MMSF, CancerCare Manitoba Foundation, CCMF, Wellcome Trust, WT, University of Manitoba, UM, Health Research Board, HRB: PHRC-20-0147, National Blood Authority, NBA, Llywodraeth Cymru, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, CTN 2014-012, Medical Research Council, MRC, National Institute for Health Research, NIHR, Department of Health and Social Care, DH, European Commission, EC: APP194811, National Heart and Lung Institute, NHLI, National Health and Medical Research Council, NHMRC: 2015-06-18, 2016-16-011, APP1101719, APP2002132, Health Research Council of New Zealand, HRC: 16/631, 447335, Monash University, MU, Ministère des Affaires Sociales et de la Santé: 215522, Seventh Framework Programme, FP7, Université Pierre et Marie Curie, UPMC, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Minderoo Foundation, Dr Fitzgerald reported receiving grants from the PREPARE Network and the European Commission. Dr Gordon reported receiving grants from the National Institute for Health Research and receiving personal fees from 30 Respiratory, GlaxoSmithKline, and Bristol Myers Squibb. Dr Gosbell reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Haniffa reported receiving grants from the Wellcome Trust Innovations Project, the Minderoo Foundation, and the UK Research and Innovation African Critical Care Registry Network. Dr Higgins reported receiving grants from the National Health and Medical Research Council, the Minderoo Foundation, and the National Blood Authority. Dr Hills reported receiving grants from the Health Research Council of New Zealand. Dr Hoad reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Horvat reported receiving grants from the National Institute of Child Health and Human Development. Dr Huang reported receiving grants from the Breast Cancer Research Foundation. Dr Lamontagne reported receiving grants from the Canadian Institutes of Health Research. Dr Lawler reported receiving consulting fees from Novartis, Coronna LLC, and Brigham and Women’s Hospital, receiving royalties from McGraw-Hill Publishing, and receiving grants from the Canadian Institutes of Health Research, the LifeArc Foundation, the National Institutes of Health, the Peter Munk Cardiac Centre, the Ted Rogers Centre for Heart Research, the Thistledown Foundation, and the province of Ontario. Dr Lorenzi reported receiving personal fees from Berry Consultants. Dr Marshall reported receiving personal fees from AM-Pharma (data and safety monitoring board chair) and Critical Care Medicine (associate editor). Dr McAuley reported receiving personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Eli Lilly, Vir Biotechnology, Faron Pharmaceuticals, and Sobi, receiving grants from the National Institute for Health Research, Wellcome Trust, Innovate UK, the Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, and holding a patent for an anti-inflammatory treatment that was issued to Queen’s University Belfast. Dr McGlothlin reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Mr Mouncey reported receiving grants from the European Union, the PREPARE Network, the National Institute for Health Research, and European Union Horizon 2020. Dr Nichol reported receiving grants from the Health Research Board of Ireland and Baxter and receiving personal fees from AM-Pharma. Dr Parke reported receiving grants from Fisher and Paykel Healthcare Ltd. Ms Parker reported receiving grants from Monash University. Mr Richardson reported receiving funding from the Welsh government. Dr Rowan reported receiving grants from the European Commission and the National Institute for Health Research. Dr Saunders reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Dr Serpa Neto reported receiving personal fees from Drager and Endpoint Health. Dr Tinmouth reported receiving grants and personal fees from the Canadian Blood Services. Ms Turner reported receiving grants from the Health Research Council of New Zealand. Dr van de Veerdonk reported receiving personal fees from Gilead, Sobi, and GlaxoSmithKline. Dr Wood reported receiving grants from the Australian Medical Research Future Fund. Dr S. Berry reported being an employee of Berry Consultants with an ownership role. Dr Lewis reported being an employee of Berry Consultants. Dr Menon reported receiving grants from the National Institute for Health Research. Dr McArthur reported receiving grants from the Health Research Council of New Zealand. Dr Zarychanski reported receiving grants from the Canadian Institutes of Health Research, the University of Manitoba, LifeArc, the Thistledown Foundation, Research Manitoba, the CancerCare Manitoba Foundation, the Victoria General Hospital Foundation, the Peter Munk Cardiac Centre, and the Manitoba Medical Services Foundation. Dr Webb reported receiving grants from the National Health and Medical Research Council and the Minderoo Foundation. Dr Shankar-Hari reported receiving grants from the National Institute for Clinical Research. No other disclosures were reported., nonprofit sponsors: Monash University, Melbourne, Australia (Australasian sponsor), Utrecht Medical Center, Utrecht, the Netherlands (European sponsor), St Michael’s Hospital, Toronto, Ontario, Canada (Canadian sponsor), and the Global Coalition for Adaptive Research, San Francisco, California (US sponsor). This study was additionally funded by grant 602525 FP7-health-2013-innovation-1 from the European Union Platform for European Preparedness Against Reemerging Epidemics, grants APP1101719 and APP1116530 from the Australian National Health and Medical Research Council, grant APP2002132 from the Australian Medical Research Future Fund, grant 16/631 from the New Zealand Health Research Council, grant 447335 from the Canadian Institutes of Health Research COVID-19 Rapid Research, grant 158584 from the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program, grant CTN 2014-012 from the Health Research Board of Ireland, grant PHRC-20-0147 from the French Ministry of Health, and grant 215522 from the Wellcome Trust Innovations Project and funding from the National Institute for Health Research, the Department of Health and Social Care, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the National Institute for Health Research, the National Institute for Health Research Imperial Biomedical Research Centre, the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the Pittsburgh Foundation, and the Minderoo Foundation. The Australian government funds the Australian Red Cross Lifeblood for the provision of blood products and services. The collection of plasma in the United Kingdom was funded by European Union SoHo grants from the Department of Health and Social Care. Dr Turgeon is the Canada Research Chair in Critical Care Neurology and Trauma. Dr McQuilten is supported by emerging leader fellowship APP194811 from the National Health and Medical Research Council. Dr Gordon is funded by research professorship 2015-06-18 from the National Institute for Health Research. Dr Shankar-Hari is funded by clinician scientist fellowship 2016-16-011 from the National Institute for Health Research., In Canada, the trial has been funded by the Canadian Institute of Health Research, Strategy for Patient-Oriented Research (CIHR-SPOR) Innovative Clinical Trials Program Grant (no. 158584) for CAD $1,497,200, for the recruitment of 300 patients., The Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium is funded by the European Union (FP7-HEALTH-2013-INNOVATION-1, grant number 602525). Within the PREPARE consortium, the trial has funding for the recruitment of approximately 4000 patients., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands (RCC-Net)., Funding sources for the REMAP-CAP trial are specified in the core protocol documents. This domain has received domain-specific funding from the Australian Medical Research Future Fund (MRFF)., reported receiving grants from the National Institute for Health Research and European Union Horizon 2020. Dr Turgeon reported receiving grants from the Canadian Institutes of Health Research. Dr McQuilten reported receiving grants from the Australian Medical Research Future Fund. Dr McVerry reported receiving grants from the Pittsburgh Foundation, the Translational Breast Cancer Research Consortium, UPMC Learning While Doing Program, National Heart, Lung, and Blood Institute, and Bayer Pharmaceuticals and receiving personal fees from Boehringer Ingelheim. Dr Annane reported receiving grants from the French Ministry of Health and Solidarity. Dr Arnold reported receiving grants from the Canadian Institutes of Health Research. Ms Beane reported receiving grants and salary support from Wellcome Trust. Ms Bentum-Puijk reported receiving grants from the European Commission and the European Union. Dr L. Berry reported receiving grants from Berry Consultants. Dr Bradbury reported receiving personal fees from Lilly, Bristol Myers Squibb, Pfizer, Bayer, Amgen, Novartis, Janssen, Portola Advisors, and Ablynx. Dr Buxton reported receiving personal fees from the Breast Cancer Research Foundation, Amgen, and Eisai. Dr Callum reported receiving grants from the Canadian Blood Services and Octapharma. Dr Cove reported receiving grants from National University Health System, receiving consulting fees from Medtronic and Baxter, and holding a US patent for removal of carbon dioxide via dialysis. Dr Daly reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Derde reported receiving grants from University Medical Center Utrecht, being a member of the COVID-19 guideline committee of the Surviving Sepsis Campaign/ European Society of Intensive Care Medicine and European Society of Intensive Care Medicine COVID-19 taskforce, and serving as chair of the Dutch intensivists taskforce acute infectious threats. Dr Detry reported receiving grants from the European Union Platform for European Preparedness Against Reemerging Epidemics (PREPARE) consortium, the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, and the UPMC Learning While Doing Program. Dr De Jong reported receiving personal fees from Roche Scientific, Shionogi Scientific, and Janssen., The current regions are: x Europe, with funding from a European Union FP7 grant (FP7-HEALTH-2013-INNOVATION-1, grant number 602525), to support the enrollment of 4000 participants. This funding terminates in 2021. x Australia and New Zealand. In Australia the project has received funding from a NHMRC Project Grant (APP1101719), to support the enrollment of 2000 participants. This funding terminates in December 2021, although some extension may be feasible. In New Zealand the project has received funding from a HRC Programme Grant (16/631), to support the enrollment of 800 participants. This funding terminates in November 2021. x Canada. In Canada the project has received funding for a CIHR grant (158584), to support the enrollment of 300 participants. This funding terminates in 2022. x United States. In the US, funding has been received from UPMC health system for recruitment internally at all UPMC hospitals (>40) and to support a US regional coordinating center. Philanthropic support is being provided through GCAR. Additional funds are being pursued., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Trials Group, the Irish Critical Care, European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), NIHR, National Institute for Health Research, Medical Microbiology and Infection Prevention, AII - Infectious diseases, and Intensive Care Medicine

Katherine D. Wick, Jeremy R. Beitler, Joseph E. Levitt, Carolyn S. Calfee, Daniel F. McAuley, Elisabeth D. Riviello, Michael A. Matthay, Djillali Annane, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Covid-19, National Institutes of Health, NIH: 5T32GM8440-24, Boehringer Ingelheim, BI, Eli Lilly and Company, Genentech, GlaxoSmithKline, GSK, Johnson and Johnson, J&J; Novartis, National Institute on Handicapped Research, NIHR, Wellcome Trust, WT, Bayer Fund, BF, Medical Research Council, MRC, Intensive Care Society, ICS: K23-HL133489, R21-HL145506, UH3HL141722, Queen's University Belfast, QUB: USB962032, Innovate UK, KDW has received funding from NIH 5T32GM8440-24. DFM: Funding for PHIND trial from Innovate UK, grants/contracts from NIHR, Wellcome Trust, MRC, Northern Ireland HSC R&D division, and Novavax as an investigator for ARDS and Covid-19 trials, patent from Queen’s Belfast University for novel treatment for inflammatory disease (USB962032), consulting fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, and Eli Lilly for the study of ARDS and Covid-19, Speaker fees from GlaxoSmithKline for educational seminars, DSMB member for Vir Biotechnology, Inc. and Faron Pharmaceuticals, Co-director of research for the Intensive Care Society, Director of EME program for MRC/NIHR. Spouse has received consultancy fees from Insmed and the California Institute for Regenerative medicine. JEL has received a grant from the NIH (UH3HL141722) to study inhaled budesonide and formoterol for the treatment of hospitalized patients with pneumonia and hypoxemia for the prevention of acute respiratory failure. JRB: Grant funding from NIH grants K23-HL133489 and R21-HL145506. Consulting fees from Sedana Medical and Biomarck Pharmaceuticals for clinical trial design/planning, and Hamilton Medical for work as a medical monitor. DA has received a public grant through the national program 'Programme d’Investissements d’avenir' under the reference ANR-18-RHUS-0004 for investigating corticosteroid therapy in COVID-19 and sepsis. This work is part of Federations Hospitalo-universitaires (FHU) Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis (SEPSIS). EDR declares no competing interests. CSC: Grant funding from the NIH for the investigation of ARDS, grant support from Roche/Genentech, and Bayer for observational studies of ARDS, consultancy fees from Roche/Genentech, Bayer, Gen1e Life Sciences, and Vasomune, fees for serving on the medical board of Prometric and Quark Pharmaceuticals, personal fees from Quantum Leap Healthcare Collaborative. MAM: Grant funding from the NIH for the investigation of ARDS, grant support from Roche/Genentech for observational studies of ARDS, consulting income from Citius Pharmaceuticals, Johnson and Johnson, and Novartis., Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Hôpital Raymond Poincaré [AP-HP], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Director of EME program for MRC/NIHR. Spouse has received consultancy fees from Insmed and the California Institute for Regenerative medicine. JEL has received a grant from the NIH (UH3HL141722) to study inhaled budesonide and formoterol for the treatment of hospitalized patients with pneumonia and hypoxemia for the prevention of acute respiratory failure. JRB: Grant funding from NIH grants K23-HL133489 and R21-HL145506. Consulting fees from Sedana Medical and Biomarck Pharmaceuticals for clinical trial design/planning, and Hamilton Medical for work as a medical monitor. DA has received a public grant through the national program 'Programme d’Investissements d’avenir' under the reference ANR-18-RHUS-0004 for investigating corticosteroid therapy in COVID-19 and sepsis. This work is part of Federations Hospitalo-universitaires (FHU) Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for Sepsis (SEPSIS). EDR declares no competing interests. CSC: Grant funding from the NIH for the investigation of, and ANR-18-RHUS-0004,RECORDS,Rapid rEcognition of CS sensitive or resistant Sepsis(2018)

Patricia Margaritte-Jeannin, Marie-Hélène Dizier, Régis Matran, Miora Valérie Andrianjafimasy, Hamida Mohamdi, Farid Zerimech, Orianne Dumas, Florence Demenais, Nicole Le Moual, Rachel Nadif, Laurent Orsi, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Merck Sharp and Dohme, MSD, Wellcome Trust, WT: WT084703MA, European Commission, EC: LSHB-CT-2006-018996- GABRIEL, Agence Nationale de la Recherche, ANR: CES-2009, Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, AFSSET: EST- 09–15, PNR-EST 2017, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES, Agir pour les Maladies Chroniques, This work was funded by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES/ AFSSET , EST- 09–15 , PNR-EST 2017), Merck Sharp & Dohme (MSD) , the national hospital program of clinical research (PHRC-National 2012, EvAdA), the National Research Agency – Health Environment, Health-Work Program ( ANR-PRSP 2009 : IAGO, ANR CES-2009), the Region Hauts de France, and the Fonds AGIR pour les maladies chroniques. Genotyping of the Epidemiological study on the genetics and environment of asthma (EGEA) was supported by grants from the European Commission (No. LSHB-CT-2006-018996- GABRIEL ) and the Wellcome Trust ( WT084703MA )., This work was funded by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES/AFSSET, EST- 09?15, PNR-EST 2017), Merck Sharp & Dohme (MSD), the national hospital program of clinical research (PHRC-National 2012, EvAdA), the National Research Agency ? Health Environment, Health-Work Program (ANR-PRSP 2009: IAGO, ANR CES-2009), the Region Hauts de France, and the Fonds AGIR pour les maladies chroniques. Genotyping of the Epidemiological study on the genetics and environment of asthma (EGEA) was supported by grants from the European Commission (No. LSHB-CT-2006-018996- GABRIEL) and the Wellcome Trust (WT084703MA)., and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Alison Wilby, Stanislas Grassin-Delyle, Zoe Kane, Ian Roberts, Haleema Shakur-Still, Joseph F. Standing, Roberto Picetti, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], Bill and Melinda Gates Foundation, BMGF: OPP1176150, Wellcome Trust, WT: WT208870/Z/17/Z, and We would like to thank all the researchers and volunteers involved in the conduct and reporting of the tranexamic acid pharmacokinetic studies without which this work would not have been possible. This study was funded by Wellcome (WT208870/Z/17/Z) and the Bill & Melinda Gates Foundation (OPP1176150).

Broberg, Karin E., Kippler, Maria J., Veldink, Jan Herman, Van Den Berg, Leonard H., Middleton, Lefkos T., Travis, Ruth C., Bergmann, Manuela M., Mancini, Francesca Romana, Katzke, Verena Andrea, Agudo, Antonio T., Gómez, Jesús Humberto, Rodríguez-Barranco, Miguel A., Trichopoulou, Antonia D., Vermeulen, Roel C.H., Peters, Susan, Broberg, Karin, Gallo, Valentina, Levi, Michael, Kippler, Maria, Vineis, Paolo, Veldink, Jan, Berg, Leonard, Middleton, Lefkos, Travis, Ruth, Bergmann, Manuela, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Elbaz, Alexis, Vlaar, Tim, Mancini, Francesca, Kühn, Tilman, Katzke, Verena, Agudo, Antonio, Goñi, Fernando, Gómez, Jesús‐humberto, Rodríguez‐barranco, Miguel, Merino, Susana, Barricarte, Aurelio, Trichopoulou, Antonia, Jenab, Mazda, Weiderpass, Elisabete, Vermeulen, Roel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), FOOD‐CT‐2005‐513943 Ministry of National Education and Religious Affairs Cancer Research UK, CRUK Wellcome Trust, WT German Cancer Research Center, DKFZ Department of Health, Australian Government Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Instituto de Salud Carlos III, ISCIII: C03/09 Stichting Diabetes Onderzoek Nederland British Heart Foundation, BHF Norges Forskningsråd QLK4CT199900927 Stroke Association European Commission, EC Deutsche Krebshilfe World Cancer Research Fund, WCRF Kreftforeningen, NCS Medical Research Council, MRC, The EPIC study is funded by a number of grants, however, no funding source had any role in the preparation of this article. The EPIC study was funded by the Europe against Cancer program of the European Commission (SANCO), Italian Association for Research on Cancer, and Italian National Research Council. In addition, the authors thank the following for their financial support: the Environmental Cancer Risk, Nutrition, and Individual Susceptibility Network of Excellence, operating within the European Union Sixth Framework Program, Priority 5: Food Quality and Safety (FOOD‐CT‐2005‐513943), European Community Fifth Framework Program (grant QLK4CT199900927), ISCIII, Red de Centros RCESP (C03/09), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia, and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health, Welfare, and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands, Swedish Cancer, Swedish Scientific Council, Regional Government of Skåne and Västerbotten, Sweden, Norwegian Cancer Society, Research Council of Norway, French League against Cancer, INSERM, Mutuelle Generale l'Education National, and IGR. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136)., and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Fulvio Ricceri, Joseph A. Rothwell, Amanda J. Cross, Graham G. Giles, Elisabete Weiderpass, Tilman Kühn, Emily Sonestedt, Yi Yang, Rudolf Kaaks, Valeria Pala, Anna Karakatsani, Dallas R. English, Rosario Tumino, Pilar Amiano, Antonia Trichopoulou, John L. Hopper, Leila Lujan-Barroso, Allison M. Hodge, Bengt Wallner, Ruth C. Travis, María Dolores López, Anne Tjønneland, Hazel M. Mitchell, Kostas Tsilidis, Domenico Palli, Harindra Jayasekara, Elio Riboli, Antonio Agudo, Robin Room, Heiner Boeing, Eva Ardanaz, Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Pietro Ferrari, Robert J. MacInnis, Susana Merino, Andrew Haydon, Eleni Peppa, Marie-Christine Boutron-Ruault, Salvatore Panico, María José Sánchez, Marc J. Gunter, Hanna Sternby, Roger L. Milne, Gianluca Severi, Ana Lucia Mayen-Chacon, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), VicHealth Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT Medical Research Council, MRC: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1 British Heart Foundation, BHF Department of Health and Social Care, DH Cancer Research UK, CRUK: C570/ A16491, C8221/A19170, C864/A14136 World Cancer Research Fund, WCRF Food Standards Agency, FSA Stroke Association European Commission, EC National Health and Medical Research Council, NHMRC: 1074383, 209057, 396414, GNT1163120 Cancer Council Victoria Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Vetenskapsrådet, VR Consiglio Nazionale delle Ricerche, CNR Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Foundation for Alcohol Research and Education, FARE Hellenic Health Foundation, HHF, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414, GNT1163120, Cancer Council Victoria (Australia), Cancer Research UK, Grant/Award Numbers: C570/ A16491, C8221/A19170, C864/A14136, Catalan Institute of Oncology ‐ ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission (Directorate General for Health and Consumer Affairs), Foundation for Alcohol Research and Education (Australia), French Ministry of Health, Grant/Award Number: Grant GR‐IARC‐2003‐09‐12‐01, Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Santé et de la Recherche Médicale (France), Italian Association for Research on Cancer and the National Research Council (Italy), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, Medical Research Council (UK), Grant/Award Numbers: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, Mutuelle Générale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK), Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), the Federal Ministry of Education and Research (Germany), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Institut Gustave Roussy Funding information, We thank Carine Biessy and Bertrand Hemon for their technical contribution to EPIC data used in this work. We are also grateful to all the EPIC participants who have been part of the project, and to the many members of the study teams who enabled this research. We thank the original MCCS investigators and the diligent team, who recruited the participants and who continue working on follow‐up, for their contribution. We also express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, the Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ‐ ICO (Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). MCCS cohort recruitment was funded by Cancer Council Victoria ( https://www.cancervic.org.au/ ) and VicHealth ( https://www.vichealth.vic.gov.au/ ). The MCCS was further supported by Australian National Health and Medical Research Council (NHMRC) ( https://www.nhmrc.gov.au/ ) grants 209057, 396414 and 1074383, and ongoing follow‐up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Harindra Jayasekara is supported by NHMRC grant GNT1163120. John L. Hopper is a NHMRC Senior Principal Research Fellow. Yi Yang is supported by a Melbourne Research Scholarship from the University of Melbourne. Robin Room's position was funded by the Foundation for Alcohol Research and Education. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and and decision to submit the manuscript for publication.

Daniel F. Schmidt, Rory P. Wilson, Melanie Waldenberger, Laura Baglietto, Harindra Jayasekara, Benjamin Lehne, Graham G. Giles, Pierre Antoine Dugué, Jaspal S. Kooner, Melissa C. Southey, Xiaochuan Wang, Annette Peters, Karl-Heinz Ladwig, Dallas R. English, John C Chambers, Jihoon E. Joo, Christian Gieger, Roger L. Milne, Chol-Hee Jung, Gianluca Severi, Enes Makalic, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Melbourne School of Population and Global Health [Melbourne], University of Melbourne, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, W2 1PG, Melbourne Bioinformatics [Australia], The University of MelbourneParkville, VIC, Australia., Department of Clinical and Experimental Medicine, University of Pisa, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), München, Technische Universität München, German Research Center for Cardiovascular Disease (DZHK), Partner site Munich Heart Alliance, Institute of Epidemiology and Medical Biometry, University of Ulm, Munich, Germany, Ealing Hospital, Imperial College Healthcare NHS Trust, Monash University [Clayton], Nanyang Technological University [Singapour], Imperial College Healthcare NHS Trust Oregon Department of Agriculture, ODA: 16/136/68 279143 Wellcome Trust, WT: 084723/Z/08/Z, 090532, RP‐PG‐0407‐10371, 098381 Cancer Council Victoria: 1026892, 1027505, 251553, 209057, 1050198, 1011618, 1074383, 504711, 1043616 Bundesministerium für Bildung und Forschung, BMBF VicHealth British Heart Foundation, BHF: SP/04/002 Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München National Institute for Health Research, NIHR National Health and Medical Research Council, NHMRC: 1088405 Horizon 2020 Framework Programme, H2020: 643774 ERAB: The European Foundation for Alcohol Research, ERAB: ERAB 2018 – EA1817 Medical Research Council, MRC: G0601966, G0700931 National Medical Research Council, NMRC: NMRC/STaR/0028/2017, and This work (MCCS) was supported by the Australian National Health and Medical Research Council (NHMRC) (Grant 1088405). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC Grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases were ascertained through the Victorian Cancer Registry (VCR) and the Australian Cancer Database (Australian Institute of Health and Welfare). The nested case‐control methylation studies were supported by the NHMRC Grants 1011618, 1026892, 1027505, 1050198, 1043616, and 1074383. M.C.S. is an NHMRC Senior Research Fellow (1061177). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research has been supported within the Munich Center of Health Sciences (MC‐Health), Ludwig‐Maximilians‐Universität, as part of LMUinnovativ. This work has received funding from the European Foundation for Alcohol Research (ERAB 2018 – EA1817). We thank all members of field staffs who were involved in the planning and conduct of the MONICA/KORA Augsburg studies. The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966, G0700931), the Wellcome Trust (084723/Z/08/Z, 090532, and 098381), the NIHR (RP‐PG‐0407‐10371), the NIHR Official Development Assistance (ODA, award 16/136/68), the European Union FP7 (EpiMigrant, 279143), and H2020 programs (iHealth‐T2D, 643774). We acknowledge support of the MRC‐PHE Centre for Environment and Health and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR, or the Department of Health. We thank the participants and research staff who made the study possible. JC is supported by the Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research Investigator (STaR) Award (NMRC/STaR/0028/2017).

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Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, 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Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs

Maya Nadimpalli, Claire D. Bourke, Elisabeth Delarocque-Astagneau, Amee R. Manges, Amy J. Pickering, Ruairi C. Robertson, Tufts University [Medford], Queen Mary University of London (QMUL), Zvitambo Institute for Maternal and Child Health Research, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Northern British Columbia [Prince George] (UNBC), British Columbia Centre for Disease Control [Vancouver] (BCCDC), Burroughs Wellcome Fund, BWF Wellcome Trust, WT: 206455/Z/17/Z National Institutes of Health, NIH: KL2TR002545 National Center for Advancing Translational Sciences, NCATS Royal Society: 206225/Z/17/Z, M.L.N. is supported by the National Center for Advancing Translational Sciences, National Institutes of Health (KL2TR002545). C.D.B. is supported by a Sir Henry Dale Postdoctoral Research Fellowship from Wellcome and the Royal Society (206225/Z/17/Z). R.C.R. is supported by a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust (206455/Z/17/Z). The funders had no role in manuscript preparation or decision to publish. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH., HAL UVSQ, Équipe, and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)

Anne Tjønneland, Claudia Agnoli, Pietro Ferrari, Pilar Amiano, Bas Bueno-de-Mesquita, Miguel Rodríguez-Barranco, Alexandra Nieters, Aurelio Barricarte, Roel Vermeulen, Elisabete Weiderpass, Giovanna Masala, José María Huerta, Marta Solans, Delphine Casabonne, Federico Canzian, Caroline Besson, Florentin Späth, Gianluca Severi, Carlotta Sacerdote, James McKay, Catalina Bonet, Sabine Naudin, Fatemeh Saberi Hosnijeh, Sofia Christakoudi, Heinz Freisling, Rosario Tumino, Kristin Benjaminsen Borch, Rudolf Kaaks, Matthias B. Schulze, Yolanda Benavente, Anja Olsen, Charlotta Rylander, Anika Knuppel, Marie Christine Boutron Ruault, Mats Jerkeman, Immunology, Centre international de Recherche sur le Cancer (CIRC), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 179 2017SGR1085 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: 205212/Z/16/Z National Research Council, NRC Medical Research Council, MRC: MR/M012190/1 Cancer Research UK, CRUK: 14136, C570/A11692, C570/A16491 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF: 01EO1303 Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR Ligue Contre le Cancer Vetenskapsrådet, VR NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN European Regional Development Fund, ERDF: ERC2009‐AdG 232997, PI13/00061, PI13/01162, PI14/01219, PI17/01280 Hellenic Health Foundation, HHF, Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme/Generalitat de Catalunya for institutional support, Grant/Award Number: 2017SGR1085, Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Cancer Research UK, Grant/Award Numbers: 14136 (to EPIC‐Norfolk), C570/A11692, C570/A16491, Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), (Spain), Danish Cancer Society (Denmark), TRANSCAN/Dutch Cancer Society, Grant/Award Number: 179, NOVEL consortium, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), European Commission (DG‐SANCO), Federal Ministry of Education and Research (BMBF), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research, Grant/Award Number: BMBF 01EO1303, German Institute of Human Nutrition Potsdam‐Rehbruecke, Nuthetal (Germany), Institut Gustave Roussy, Institut National de la Sante et de la Recherche Medicale (France), International Agency for Research on Cancer, Ligue Natinale Contre le Cancer, LK Research Funds, Medical Research Council, Grant/Award Numbers: 1000143 (to EPIC‐Norfolk), MR/M012190/1 (to EPIC‐Oxford), Mutuelle Generale de l'Education Nationale, Netherlands Cancer Registry (NKR), Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe, Grant/Award Numbers: PI13/00061 (to Granada), PI13/01162 (to EPIC‐Murcia), PI17/01280, PI14/01219 (to Barcelona), Statistics Netherlands (The Netherlands), Grant/Award Number: Grant number: ERC2009‐AdG 232997, Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Vasterbotten (Sweden), the Hellenic Health Foundation (Greece), Wellcome Trust, Grant/Award Number: 205212/Z/16/Z, and World Cancer Research Fund (WCRF) Funding information

Audrey Bernut, Catherine A. Loynes, R. Andres Floto, Stephen A. Renshaw, Floto, Andres [0000-0002-2188-5659], Apollo - University of Cambridge Repository, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Sheffield [Sheffield], University of Cambridge [UK] (CAM), Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, United Kingdom., University of Sheffield Wellcome Trust, WT: GR077544AIA H2020-MSCA-IF-2016 160161 751977, MR/M004864/1, MR/N02995X/1 Medical Research Council, MRC: G0700091, We acknowledge the Bateson Centre aquarium and Wolfson Light Microscopy Facility [MRC grant (G0700091) and Wellcome Trust grant (GR077544AIA)] at the University of Sheffield. We would like to thank David Drew for technical assistance. This manuscript has been released as a pre-print at Bernut et al. (55). Funding. This study was supported by the European Community's Horizon 2020-Research and Innovation Framework Program (H2020-MSCA-IF-2016) under the Marie-Curie IF CFZEBRA (751977) to AB, MRC Program Grants (MR/M004864/1) to SR, the MRC AMR Theme award (MR/N02995X/1) to AB and SR, and CF Trust workshop funding (160161) to AB, RF, and SR., and HAL UVSQ, Équipe

Magritt Brustad, Veronika Fedirko, Marc J. Gunter, Anja Olsen, Antonia Trichopoulou, Geneviève Nicolas, Anna Karakatsani, Veronique Chajes, Gianluca Severi, Elom K. Aglago, Eva Ardanaz, Aurora Perez-Cornago, Kim Overvad, Cristina Lasheras, Salvatore Panico, Verena Katzke, Bas Bueno-de-Mesquita, José María Huerta, Neil Murphy, Christina C. Dahm, Maria Wennberg, Teresa Norat, Bodil Ohlsson, Elisabete Weiderpass, Antonio Agudo, Heather Ward, Anne Tjønneland, Valeria Pala, Tilman Kühn, Bethany Van Guelpen, Guri Skeie, Rosario Tumino, María José Sánchez, A. M. May, Corinne Casagrande, Jeroen W.G. Derksen, Marie-Christine Boutron-Ruault, Elio Riboli, Agnès Fournier, Sophie Hellstrand, Inge Huybrechts, Georgia Martimianaki, Alessio Naccarati, Tobias Pischon, Amanda J. Cross, Pilar Amiano, Domenico Palli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), RD06/0020 6236 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: C570/A16491, C8221/A19170, MR/M012190/1 National Research Council, NRC Medical Research Council, MRC British Heart Foundation, BHF Cancer Research UK, CRUK World Cancer Research Fund, WCRF: WCRF 2013/1002 Food Standards Agency, FSA Stroke Association European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Associazione Iblea per la Ricerca Epidemiologica, AIRE Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Fondation Gustave Roussy Hellenic Health Foundation, HHF, Funding Supported by a grant from the World Cancer Research Fund ( WCRF ) to Marc Gunter (grant number: WCRF 2013/1002 ). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer . The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l'Education Nationale , and Institut National de la Santé et de la Recherche Médicale ( INSERM ) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), and Federal Ministry of Education and Research ( BMBF ) (Germany), Hellenic Health Foundation , Stavros Niarchos Foundation , and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer ( AIRC ), National Research Council , and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu ( AVIS ) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry ( NKR ), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), and Statistics Netherlands (the Netherlands), Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucía , Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II ( ISCIII RETIC) ( RD06/0020 ) (Spain), Swedish Cancer Society , Swedish Scientific Council , and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK , Medical Research Council , Stroke Association , British Heart Foundation , Department of Health , Food Standards Agency , the Wellcome Trust (UK), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Stephen P. Jackson, Mareike Herzog, Alejandra Bruna, Luca Pellegrini, Violeta Serra, Mark J. O'Connor, Zhongwu Lai, Chloé Lescale, Jacqueline J.L. Jacobs, Fengtang Yang, Jonathan Lam, Matylda Sczaniecka-Clift, Abigail Shea, Carlos Caldas, Matthias Ostermaier, Gabriel Balmus, Julia Coates, Wenming Wei, Inge de Krijger, Yaron Galanty, Mukerrem Demir, Ludovic Deriano, Petra Beli, Domenic Pilger, Harveer Dev, Rimma Belotserkovskaya, Alistair Martin, Beiyuan Fu, Ting-Wei Will Chiang, Qian Wu, Dev, Harveer [0000-0003-2874-6894], Yang, Fengtang [0000-0002-3573-2354], Balmus, Gabriel [0000-0003-2872-4468], Serra, Violeta [0000-0001-6620-1065], Beli, Petra [0000-0001-9507-9820], Pellegrini, Luca [0000-0002-9300-497X], Deriano, Ludovic [0000-0002-9673-9525], Jacobs, Jacqueline JL [0000-0002-7704-4795], Jackson, Stephen P [0000-0001-9317-7937], Apollo - University of Cambridge Repository, Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge [UK] (CAM), Department of Biochemistry [Cambridge], Cambridge University Hospitals - NHS (CUH), Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris] (IP), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Cancer Research UK Cambridge Institute [Cambridge, Royaume-Uni] (CRUK), Institute of Molecular Biology (IMB), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Wellcome Trust Sanger Institute [Hinxton, UK], AstraZeneca US [Waltham, USA], AstraZeneca [Cambridge, UK], The Wellcome Trust Sanger Institute [Cambridge], Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], The SPJ lab is largely funded by a Cancer Research UK (CRUK) Program Grant, C6/A18796, and a Wellcome Trust (WT) Investigator Award, 206388/Z/17/Z. Core infrastructure funding was provided by CRUK grant C6946/A24843 and WT grant WT203144. S.P.J. receives a salary from the University of Cambridge. H.D. is funded by WT Clinical Fellowship 206721/Z/17/Z. TWC was supported by a Cambridge International Scholarship. D.P. is funded by Cancer Research UK studentship C6/A21454. The P.B. lab is supported by the Emmy Noether Program (BE 5342/1-1) from the German Research Foundation and a Marie Curie Career Integration Grant from the European Commission (630763). The L.P. lab is funded by the WT (investigator award 104641/Z/14/Z) and the Medical Research Council (project grant MR/N000161/1). The C.C. lab was supported with funding from CRUK. The J.J. lab was supported by the European Research Council grant ERC-StG 311565, The Dutch Cancer Society (KWF) grant KWF 10999, and the Netherlands Organization for Scientific Research (NWO) as part of the National Roadmap Large-scale Research Facilities of the Netherlands, Proteins@Work (project no. 184.032.201 to the Proteomics Facility of the Netherlands Cancer Institute). The L.D. lab is funded by the Institut Pasteur, the Institut National du Cancer (no. PLBIO16-181) and the European Research Council (starting grant agreement no. 310917). W.W. is part of the Pasteur–Paris University (PPU) International PhD program and this project received funding from the CNBG company, China. Q.W. is funded by the Wellcome Trust (200814/Z/16/Z ). The V.S. lab work was funded by the Instituto de Salud Carlos III (ISCIII), an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (PI17-01080 to VS), the European Research Area-NET, Transcan-2 (AC15/00063), a non-commercial research agreement with AstraZeneca UK, and structural funds from the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 540) and the Orozco Family. V.S. received a salary and travel support to C.C.’s lab from ISCIII (CP14/00228, MV15/00041) and the FERO Foundation., The authors thank all S.P.J. laboratory members for support and advice, and Cambridge colleagues N. Lawrence for OMX super-resolution microscopy support and R. Butler for help with computational image analyses and programming. The authors also thank S. Selivanova and S. Hough for help with plasmid amplification, sample preparation and tissue culture maintenance, K. Dry for extensive editorial assistance, F. Muñoz-Martinez for assistance with CRISPR–Cas9 knockout generation, L. Radu for assistance with protein purification, C. Lord (Institute of Cancer Research, London) for SUM149PT cells, D. Durocher (University of Toronto, Canada) for U2OS LacSceIII cells, F. Alt (Harvard University, USA) for CH12F3 cells and 53bp1 knockout CH12F3 cell clones, T. Honjo (Kyoto University, Japan) for permission to use the CH12F3 cell line, and J. Serrat in the Jacobs lab for technical assistance, Institut Pasteur [Paris], and Johannes Gutenberg - Universität Mainz (JGU)

Banzhaf, Manuel, Yau, Hamish Cl, Verheul, Jolanda, Lodge, Adam, Kritikos, George, Mateus, André, Cordier, Baptiste, Hov, Ann Kristin, Stein, Frank, Wartel, Morgane, Pazos, Manuel, Solovyova, Alexandra S, Breukink, Eefjan, van Teeffelen, Sven, Savitski, Mikhail M, den Blaauwen, Tanneke, Typas, Athanasios, Vollmer, Waldemar, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Bacterial Cell Biology & Physiology (SILS, FNWI), European Molecular Biology Laboratory [Heidelberg] (EMBL), Newcastle University [Newcastle], University of Amsterdam [Amsterdam] (UvA), Morphogénèse et Croissance microbiennes / Microbial Morphogenesis and Growth, Institut Pasteur [Paris], Utrecht University [Utrecht], Wellcome Trust (WT). Grant Number: 101824/Z/13/ZUK Research and Innovation|Medical Research Council (MRC). Grant Number: MR/N002679/1Royal Society. Grant Number: RGS\R1\191041European Molecular Biology Laboratory (EMBL). Grant Number: 664726EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC). Grant Number: 679980Agence Nationale de la Recherche (ANR). Grant Number: ANR‐10‐LABX‐62‐IBEIDVolkswagen Foundation (VolkswagenStiftung), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 679980,H2020,ERC-2015-STG,RCSB(2016), and Institut Pasteur [Paris] (IP)