Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes.
Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: jmanto@isglobal.org.
Josep M
JM
Anto
University Hospital, Montpellier, France; MACVIA-France, Contre les MAladies Chroniques pour un Vieillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier; INSERM, U1168, Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, and UVSQ, UMR-S 1168, Univ Versaille St-Quentin-en-Yvelynes, Montigny le Bretonneux, France. Electronic address: jean.bousquet@orange.fr.
Jean
J
Bousquet
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Mubeccel
M
Akdis
European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, France.
Charles
C
Auffray
Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, and the Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.
Thomas
T
Keil
Department of Public health and health products, Paris Descartes University-Sorbonne Paris Cité, EA 4064, and Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
Isabelle
I
Momas
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Dirkje S
DS
Postma
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Rudolf
R
Valenta
Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Magnus
M
Wickman
UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, France.
Anne
A
Cambon-Thomsen
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
Tari
T
Haahtela
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
Bart N
BN
Lambrecht
Department of Paediatrics, Oslo University Hospital, and the Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Karin C
KC
Lodrup Carlsen
Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gerard H
GH
Koppelman
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Jordi
J
Sunyer
Allergy-Centre-Charité at the Department of Dermatology, Charité-Universitätsmedizin Berlin, and Secretary General of the Global Allergy and Asthma European Network (GA(2)LEN), Berlin, Germany.
Torsten
T
Zuberbier
EPAR U707 INSERM, Paris and EPAR UMR-S UPMC, Paris VI, Paris, France.
Isabelle
I
Annesi-Maesano
Onmedic Networks, Barcelona, Spain.
Albert
A
Arno
Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
Carsten
C
Bindslev-Jensen
EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium.
Giuseppe
G
De Carlo
Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy.
Francesco
F
Forastiere
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Joachim
J
Heinrich
Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland.
Marek L
ML
Kowalski
Biomax Informatics AG, Munich, Germany.
Dieter
D
Maier
Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Erik
E
Melén
Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Henriette A
HA
Smit
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Marie
M
Standl
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom.
John
J
Wright
Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, and Astrid Lindgren Children's Hospital, Department of Pediatric Pulmonology and Allergy, Karolinska University Hospital, Stockholm, Sweden.
Anna
A
Asarnoj
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Marta
M
Benet
Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; St John's Institute of Dermatology, King's College London, London, United Kingdom.
Natalia
N
Ballardini
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Judith
J
Garcia-Aymerich
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
Ulrike
U
Gehring
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Stefano
S
Guerra
Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin, Berlin, Germany.
Cynthia
C
Hohmann
Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Inger
I
Kull
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Christian
C
Lupinek
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Mariona
M
Pinart
Department of Paediatrics, Oslo University Hospital, and the Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ingebjorg
I
Skrindo
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, and Department of ENT diseases, Karolinska University Hospital, Stockholm, Sweden.
Marit
M
Westman
Inserm Transfert, Paris, France.
Delphine
D
Smagghe
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Cezmi
C
Akdis
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Niklas
N
Andersson
ENT Department, Ghent University Hospital, Ghent, Belgium.
Claus
C
Bachert
European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, France.
Stephane
S
Ballereau
Environment and Health Area, Centre for Public Health Research (CSISP); CIBERESP, Department of Nursing, University of Valencia, Valencia, Spain.
Ferran
F
Ballester
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Xavier
X
Basagana
MACVIA-France, Contre les MAladies Chroniques pour un Vieillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier.
Anna
A
Bedbrook
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Anna
A
Bergstrom
Research Institute, Department of Pediatrics, Marien-Hospital, Wesel, Germany.
Andrea
A
von Berg
Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands; Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
Bert
B
Brunekreef
INSERM, U1168, Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, and UVSQ, UMR-S 1168, Univ Versaille St-Quentin-en-Yvelynes, Montigny le Bretonneux, France.
Emilie
E
Burte
Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Kai-Hakon
KH
Carlsen
Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece.
Leda
L
Chatzi
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
Jonathan M
JM
Coquet
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Mirela
M
Curin
Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France.
Pascal
P
Demoly
Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
Esben
E
Eller
Department of Medicine and Public Health, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Maria Pia
MP
Fantini
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
Leena
L
von Hertzen
Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Vergard
V
Hovland
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Benedicte
B
Jacquemin
Allergology Department, Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand-Trousseau (APHP), and Sorbonne Universités, UPMC Univ Paris Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe EPAR, Paris, France.
Jocelyne
J
Just
Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin, Berlin, Germany.
Theresa
T
Keller
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Renata
R
Kiss
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Manolis
M
Kogevinas
Division of Paediatric Gastroenterology and Hepatology, Ludwig-Maximilians-Universität of Munich, Munich, Germany.
Sibylle
S
Koletzko
Department for Pediatric Pneumology and Immunology, Charité Medical University, Berlin, Germany.
Susanne
S
Lau
Department of Environmental Immunology/Core Facility Studies, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.
Irina
I
Lehmann
Institut Albert Bonniot à Grenoble (Institute for Advanced Biosciences), Grenoble, France.
Nicolas
N
Lemonnier
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
Mika
M
Mäkelä
Chemotargets SL and Chemogenomics Laboratory, GRIB Unit, IMIM-Hospital del Mar and University Pompeu Fabra, Barcelona, Spain.
Jordi
J
Mestres
Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Peter
P
Mowinckel
INSERM, U1168, Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, and UVSQ, UMR-S 1168, Univ Versaille St-Quentin-en-Yvelynes, Montigny le Bretonneux, France.
Rachel
R
Nadif
Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Martijn C
MC
Nawijn
European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL, Université de Lyon, Lyon, France.
Johan
J
Pellet
Département de pédiatrie, CHU de Grenoble, Grenoble, France.
Isabelle
I
Pin
Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy.
Daniela
D
Porta
Department of Public health and health products, Paris Descartes University-Sorbonne Paris Cité, EA 4064, and Paris Municipal Department of Social Action, Childhood, and Health, Paris, France.
Fanny
F
Rancière
UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, France.
Emmanuelle
E
Rial-Sebbag
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
Yvan
Y
Saeys
VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
Martijn J
MJ
Schuijs
Inserm, U823, Grenoble, France.
Valerie
V
Siroux
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Christina G
CG
Tischer
ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; ib-salut, Area de Salut de Menorca, Menorca, Spain.
Mathies
M
Torrent
INSERM, U1168, Ageing and chronic diseases Epidemiological and public health approaches, Villejuif, and UVSQ, UMR-S 1168, Univ Versaille St-Quentin-en-Yvelynes, Montigny le Bretonneux, France.
Raphaelle
R
Varraso
Biomax Informatics AG, Munich, Germany.
Kalus
K
Wenzel
Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Cheng-Jian
CJ
Xu
D000293:Adolescent; D000485:Allergens / Q000276:immunology*; D000818:Animals; D002648:Child; D015331:Cohort Studies; D015897:Comorbidity; D005060:Europe / Q000453:epidemiology; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D010641:Phenotype; D057170:Translational Research, Biomedical; D055815:Young Adult
D000485:Allergens; D007073:Immunoglobulin E
Asthma; allergy; atopic dermatitis; rhinitis