Article open access publication

Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes

Journal of Allergy and Clinical Immunology, Elsevier, ISSN 0091-6749

Volume 139, 2, 2017

DOI:10.1016/j.jaci.2016.12.940, Dimensions: pub.1083691317, PMID: 28183433,


Anto, Josep M. * (1) (2) (3) (4)
Bousquet, Jean * (5) (6) (7)
Sunyer, J Oriol (1) (2) (3) (4)
Garcia-Aymerich, Judith (1) (2) (3) (4)
Kull, Inger (14) (30)
Brunekreef, Bert (28) (32)
Kogevinas, Manolis (1) (2) (3) (4)
Torrent, Mathies (1) (45)

* Corresponding author



  1. (1) ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
  2. (2) Hospital Del Mar, grid.411142.3
  3. (3) Institute of Health Carlos III, grid.413448.e
  4. (4) Pompeu Fabra University, grid.5612.0
  5. (5) MACVIA-France, Contre les MAladies Chroniques pour un Vieillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier
  6. (6) French Institute of Health and Medical Research, grid.7429.8
  7. (7) University Hospital of Montpellier, grid.157868.5
  8. (8) University of Zurich, grid.7400.3
  9. (9) University of Lyon System, grid.25697.3f
  10. (10) Charité, grid.6363.0
  11. (11) 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
  12. (12) University Medical Center Groningen, grid.4494.d
  13. (13) Medical University of Vienna, grid.22937.3d
  14. (14) Stockholm South General Hospital, grid.416648.9
  15. (15) University of Toulouse, grid.11417.32
  16. (16) Helsinki University Central Hospital, grid.15485.3d
  17. (17) Ghent University, grid.5342.0
  18. (18) Department of Paediatrics, Oslo University Hospital, and the Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  19. (19) Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  20. (20) EPAR U707 INSERM, Paris and EPAR UMR-S UPMC, Paris VI, Paris, France
  21. (21) Onmedic Networks, Barcelona, Spain
  22. (22) Odense University Hospital, grid.7143.1, Southern Denmark Region
  23. (23) European Federation of Allergy and Airways Diseases Patients Associations, grid.434606.3
  24. (24) Department of Epidemiology, Regional Health Service Lazio Region, Rome, Italy
  25. (25) Helmholtz Zentrum München, grid.4567.0
  26. (26) Medical University of Lodz, grid.8267.b
  27. (27) Biomax Informatics (Germany), grid.424158.e
  28. (28) Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
  29. (29) Bradford Royal Infirmary, grid.418447.a
  30. (30) Karolinska Institute, grid.4714.6
  31. (31) King's College London, grid.13097.3c
  32. (32) Utrecht University, grid.5477.1
  33. (33) Inserm Transfert, grid.14498.30
  34. (34) Ghent University Hospital, grid.410566.0
  35. (35) Environment and Health Area, Centre for Public Health Research (CSISP); CIBERESP, Department of Nursing, University of Valencia, Valencia, Spain
  36. (36) Research Institute, Department of Pediatrics, Marien-Hospital, Wesel, Germany
  37. (37) University of Oslo, grid.5510.1
  38. (38) University of Crete, grid.8127.c
  39. (39) University of Bologna, grid.6292.f
  40. (40) Sorbonne University, grid.462844.8
  41. (41) Ludwig Maximilian University of Munich, grid.5252.0
  42. (42) Helmholtz Centre for Environmental Research, grid.7492.8
  43. (43) Institut Albert Bonniot, grid.418110.d
  44. (44) Centre Hospitalier Universitaire de Grenoble, grid.410529.b
  45. (45) ib-salut, Area de Salut de Menorca, Menorca, Spain


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.


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