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1. Plasticity of Individual Lung Function States from Childhood to Adulthood.

Author

Wang G, Hallberg J, Faner R, Koefoed HJ, Kebede Merid S, Klevebro S, Björkander S, Gruzieva O, Pershagen G, van Hage M, Guerra S, Bottai M, Georgelis A, Gehring U, Bergström A, Vonk JM, Kull I, Koppelman GH, Agusti A, and Melén E

Subjects
Child, Humans, Adolescent, Young Adult, Lung, Respiratory Function Tests, Respiratory Sounds, Asthma, Hypersensitivity diagnosis
Abstract

Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Prebronchodilator FEV 1 z -scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) ( N  = 3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA (Prevention and Incidence of Asthma and Mite Allergy) cohort. Measurements and Main Results: Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low or very low states and 36 (2.4%) participants with normal or high or very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions: Individual lung function states during childhood are plastic, including catch-up and growth failure.

Published
2023
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2. A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents.

Author

Lemonnier N, Melén E, Jiang Y, Joly S, Ménard C, Aguilar D, Acosta-Perez E, Bergström A, Boutaoui N, Bustamante M, Canino G, Forno E, Ramon González J, Garcia-Aymerich J, Gruzieva O, Guerra S, Heinrich J, Kull I, Ibarluzea Maurolagoitia J, Santa-Marina Rodriguez L, Thiering E, Wickman M, Akdis C, Akdis M, Chen W, Keil T, Koppelman GH, Siroux V, Xu CJ, Hainaut P, Standl M, Sunyer J, Celedón JC, Maria Antó J, and Bousquet J

Subjects
Adolescent, Child, Humans, Multimorbidity, Transcriptome, Asthma epidemiology, Asthma genetics, Hypersensitivity epidemiology, Hypersensitivity genetics, Rhinitis epidemiology, Rhinitis genetics, Rhinitis, Allergic epidemiology, Rhinitis, Allergic genetics
Abstract

Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes., Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease., Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found., Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Published
2020
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3. Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

Author

Benet M, Albang R, Pinart M, Hohmann C, Tischer CG, Annesi-Maesano I, Baïz N, Bindslev-Jensen C, Lødrup Carlsen KC, Carlsen KH, Cirugeda L, Eller E, Fantini MP, Gehring U, Gerhard B, Gori D, Hallner E, Kull I, Lenzi J, McEachan R, Minina E, Momas I, Narduzzi S, Petherick ES, Porta D, Rancière F, Standl M, Torrent M, Wijga AH, Wright J, Kogevinas M, Guerra S, Sunyer J, Keil T, Bousquet J, Maier D, Anto JM, and Garcia-Aymerich J

Subjects
Child, Child, Preschool, Europe epidemiology, Female, Humans, Infant, Infant, Newborn, Male, Pregnancy, Asthma epidemiology, Cohort Studies, Hypersensitivity epidemiology, Research Design standards
Abstract

The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Published
2019
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4. Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes.

Author

Anto JM, Bousquet J, Akdis M, Auffray C, Keil T, Momas I, Postma DS, Valenta R, Wickman M, Cambon-Thomsen A, Haahtela T, Lambrecht BN, Lodrup Carlsen KC, Koppelman GH, Sunyer J, Zuberbier T, Annesi-Maesano I, Arno A, Bindslev-Jensen C, De Carlo G, Forastiere F, Heinrich J, Kowalski ML, Maier D, Melén E, Smit HA, Standl M, Wright J, Asarnoj A, Benet M, Ballardini N, Garcia-Aymerich J, Gehring U, Guerra S, Hohmann C, Kull I, Lupinek C, Pinart M, Skrindo I, Westman M, Smagghe D, Akdis C, Andersson N, Bachert C, Ballereau S, Ballester F, Basagana X, Bedbrook A, Bergstrom A, von Berg A, Brunekreef B, Burte E, Carlsen KH, Chatzi L, Coquet JM, Curin M, Demoly P, Eller E, Fantini MP, von Hertzen L, Hovland V, Jacquemin B, Just J, Keller T, Kiss R, Kogevinas M, Koletzko S, Lau S, Lehmann I, Lemonnier N, Mäkelä M, Mestres J, Mowinckel P, Nadif R, Nawijn MC, Pellet J, Pin I, Porta D, Rancière F, Rial-Sebbag E, Saeys Y, Schuijs MJ, Siroux V, Tischer CG, Torrent M, Varraso R, Wenzel K, and Xu CJ

Subjects
Adolescent, Animals, Child, Cohort Studies, Comorbidity, Europe epidemiology, Female, Gene Expression Profiling, Genome-Wide Association Study, Humans, Hypersensitivity epidemiology, Hypersensitivity genetics, Immunization, Immunoglobulin E metabolism, Phenotype, Translational Research, Biomedical, Young Adult, Allergens immunology, Hypersensitivity immunology
Abstract

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., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Published
2017
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5. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

Author

Bousquet J, Anto JM, Akdis M, Auffray C, Keil T, Momas I, Postma DS, Valenta R, Wickman M, Cambon-Thomsen A, Haahtela T, Lambrecht BN, Lodrup Carlsen KC, Koppelman GH, Sunyer J, Zuberbier T, Annesi-Maesano I, Arno A, Bindslev-Jensen C, De Carlo G, Forastiere F, Heinrich J, Kowalski ML, Maier D, Melén E, Palkonen S, Smit HA, Standl M, Wright J, Asarnoj A, Benet M, Ballardini N, Garcia-Aymerich J, Gehring U, Guerra S, Hohman C, Kull I, Lupinek C, Pinart M, Skrindo I, Westman M, Smagghe D, Akdis C, Albang R, Anastasova V, Anderson N, Bachert C, Ballereau S, Ballester F, Basagana X, Bedbrook A, Bergstrom A, von Berg A, Brunekreef B, Burte E, Carlsen KH, Chatzi L, Coquet JM, Curin M, Demoly P, Eller E, Fantini MP, Gerhard B, Hammad H, von Hertzen L, Hovland V, Jacquemin B, Just J, Keller T, Kerkhof M, Kiss R, Kogevinas M, Koletzko S, Lau S, Lehmann I, Lemonnier N, McEachan R, Mäkelä M, Mestres J, Minina E, Mowinckel P, Nadif R, Nawijn M, Oddie S, Pellet J, Pin I, Porta D, Rancière F, Rial-Sebbag A, Saeys Y, Schuijs MJ, Siroux V, Tischer CG, Torrent M, Varraso R, De Vocht J, Wenger K, Wieser S, and Xu C

Subjects
Disease Management, European Union, Health Policy, Humans, Hypersensitivity etiology, Hypersensitivity prevention & control, Immunization, Immunoglobulin E immunology, Inventions, Prognosis, World Health Organization, Hypersensitivity diagnosis, Hypersensitivity therapy, Precision Medicine methods, Systems Biology methods
Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda., (© 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Published
2016
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6. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.

Author

Bousquet J, Anto JM, Wickman M, Keil T, Valenta R, Haahtela T, Lodrup Carlsen K, van Hage M, Akdis C, Bachert C, Akdis M, Auffray C, Annesi-Maesano I, Bindslev-Jensen C, Cambon-Thomsen A, Carlsen KH, Chatzi L, Forastiere F, Garcia-Aymerich J, Gehrig U, Guerra S, Heinrich J, Koppelman GH, Kowalski ML, Lambrecht B, Lupinek C, Maier D, Melén E, Momas I, Palkonen S, Pinart M, Postma D, Siroux V, Smit HA, Sunyer J, Wright J, Zuberbier T, Arshad SH, Nadif R, Thijs C, Andersson N, Asarnoj A, Ballardini N, Ballereau S, Bedbrook A, Benet M, Bergstrom A, Brunekreef B, Burte E, Calderon M, De Carlo G, Demoly P, Eller E, Fantini MP, Hammad H, Hohman C, Just J, Kerkhof M, Kogevinas M, Kull I, Lau S, Lemonnier N, Mommers M, Nawijn M, Neubauer A, Oddie S, Pellet J, Pin I, Porta D, Saes Y, Skrindo I, Tischer CG, Torrent M, and von Hertzen L

Subjects
Antibody Specificity immunology, Comorbidity, Female, Genetic Predisposition to Disease, Humans, Hypersensitivity epidemiology, Immunization, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Allergens immunology, Hypersensitivity etiology, Hypersensitivity metabolism, Immunoglobulin E immunology, Signal Transduction
Abstract

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2015
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7. The locus C11orf30 increases susceptibility to poly-sensitization.

Author

Amaral AF, Minelli C, Guerra S, Wjst M, Probst-Hensch N, Pin I, Svanes C, Janson C, Heinrich J, and Jarvis DL

Subjects
Adult, Alleles, Europe epidemiology, Female, Gene Frequency, Genotype, Health Surveys, Humans, Hypersensitivity epidemiology, Immunoglobulin E immunology, Male, Polymorphism, Single Nucleotide, Skin Tests, Allergens immunology, Genetic Loci, Genetic Predisposition to Disease, Hypersensitivity genetics, Hypersensitivity immunology, Neoplasm Proteins genetics, Nuclear Proteins genetics, Repressor Proteins genetics
Abstract

A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2015
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8. Systematic Review on the Definition of Allergic Diseases in Children: The MeDALL Study.

Author

Pinart M, Albang R, Maier D, Duran-Tauleria E, Mena G, Gimeno-Santos E, Solà I, Garcia-Aymerich J, Guerra S, Stein RT, Benet M, Carlsen KH, Herr M, Jacquemin B, Momas I, Pin I, Rancière F, Smit HA, Varraso R, Bonfill X, Keil T, Bousquet J, and Antó JM

Subjects
Child, Humans, Hypersensitivity diagnosis, Hypersensitivity physiopathology, Hypersensitivity classification, Phenotype
Abstract

Background: During the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis., Methods: We conducted a search of MEDLINE up to December 2012, to identify relevant original studies published in the English language that examine at least one objective of this systematic review in subjects aged 0-18 years. The screening of titles and abstracts and the extraction of data were conducted independently by two reviewers., Results: From a total of 13,767 citations, 197 studies met the criteria for inclusion, with 54% being cohort studies. Allergic diseases were studied as a single entity in 55% (109/197) of the studies or in the context of multimorbidity in 45%. Asthma accounted for 81.7% of the studies examining single diseases. Overall, up to 33 different phenotypes of allergic disease were reported. Transient early, late-onset and persistent wheeze were the most frequently reported phenotypes. Most studies (78%) used questionnaires. The skin-prick test was the preferred measurement of sensitization (64%). Spirometry and bronchial hyperresponsiveness were assessed in one third of the studies, peak flow rate in 8.6% and disease severity in 35%., Conclusions: Studies reporting phenotypes of allergic diseases in children are highly heterogeneous and often lack objective phenotypical measures. A concerted effort to standardize methods and terminology is necessary., (© 2015 S. Karger AG, Basel.)

Published
2015
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9. Effects of prolonged breastfeeding and colostrum fatty acids on allergic manifestations and infections in infancy.

Author

Morales E, García-Esteban R, Guxens M, Guerra S, Mendez M, Moltó-Puigmartí C, Lopez-Sabater MC, and Sunyer J

Subjects
Adult, Female, Humans, Hypersensitivity epidemiology, Infant, Infant, Newborn, Infections epidemiology, Male, Odds Ratio, Pregnancy, Risk, Breast Feeding, Colostrum chemistry, Fatty Acids, Unsaturated physiology, Hypersensitivity etiology, Infections etiology
Abstract

Background: In developed countries World Health Organization recommendation of 6 months' exclusive breastfeeding is under debate., Objective: We assessed the impact of predominant breastfeeding (PBF) duration and colostrum long-chain polyunsaturated fatty acids (LC-PUFAs) profile on the risk of allergic manifestations (wheezing and atopic eczema) and infections [low respiratory tract infections (LRTIs) and gastroenteritis] in infancy., Methods: Information on child feeding practices was obtained from 580 infants of a pregnancy cohort. Presence of infant's health outcomes was documented through questionnaires at 6 and 14 months of age. The LC-PUFAs were measured in colostrum. Adjusted odds ratios (adjOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models., Results: In comparison with never breastfeeding, PBF for 4-6 months was associated with lower risk of wheezing (adjOR = 0.53; 95% CI, 0.32, 0.89), LRTIs (adjOR = 0.51; 95% CI, 0.31, 0.83) and atopic eczema (adjOR = 0.58; 95% CI, 0.32, 1.04) between months 7 and 14 of life. Results of a risk period-specific analysis (restricted to infants at risk for outcome onset after 6 months of age), showed no indication for reverse causation (results were not very different compared with an overall analysis). Predominantly breastfeeding for 4-6 months was associated with lower risk of gastroenteritis during the first 6 months of life (adjOR = 0.34; 95% CI, 0.18, 0.64). Among breastfed infants higher doses of arachidonic acid (AA), docosahexaenoic acid, and total n-3 in were associated with a decreased risk of gastroenteritis, but no association was found for allergic manifestations or LRTI., Conclusions and Clinical Relevance: Promotion of PBF for 4-6 months could reduce the burden of allergic manifestations and infections in infancy. Beneficial effects of breastfeeding on gastroenteritis were explained in part by exposure to higher doses of n-3 and AA received from colostrum. No significant effects from fatty acid dose were found on risk of allergic manifestations or LRTIs., (© 2012 Blackwell Publishing Ltd.)

Published
2012
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10. Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.

Author

Antó JM, Pinart M, Akdis M, Auffray C, Bachert C, Basagaña X, Carlsen KH, Guerra S, von Hertzen L, Illi S, Kauffmann F, Keil T, Kiley JP, Koppelman GH, Lupinek C, Martinez FD, Nawijn MC, Postma DS, Siroux V, Smit HA, Sterk PJ, Sunyer J, Valenta R, Valverde S, Akdis CA, Annesi-Maesano I, Ballester F, Benet M, Cambon-Thomsen A, Chatzi L, Coquet J, Demoly P, Gan W, Garcia-Aymerich J, Gimeno-Santos E, Guihenneuc-Jouyaux C, Haahtela T, Heinrich J, Herr M, Hohmann C, Jacquemin B, Just J, Kerkhof M, Kogevinas M, Kowalski ML, Lambrecht BN, Lau S, Lødrup Carlsen KC, Maier D, Momas I, Noel P, Oddie S, Palkonen S, Pin I, Porta D, Punturieri A, Rancière F, Smith RA, Stanic B, Stein RT, van de Veen W, van Oosterhout AJ, Varraso R, Wickman M, Wijmenga C, Wright J, Yaman G, Zuberbier T, and Bousquet J

Subjects
Adolescent, Animals, Child, Child, Preschool, Epigenesis, Genetic, Humans, Hypersensitivity epidemiology, Hypersensitivity genetics, Research, Risk Factors, Young Adult, Hypersensitivity immunology, Immunoglobulin E immunology, Phenotype
Abstract

Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human in vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Published
2012
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11. Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Author

Bousquet J, Anto JM, Demoly P, Schünemann HJ, Togias A, Akdis M, Auffray C, Bachert C, Bieber T, Bousquet PJ, Carlsen KH, Casale TB, Cruz AA, Keil T, Lodrup Carlsen KC, Maurer M, Ohta K, Papadopoulos NG, Roman Rodriguez M, Samolinski B, Agache I, Andrianarisoa A, Ang CS, Annesi-Maesano I, Ballester F, Baena-Cagnani CE, Basagaña X, Bateman ED, Bel EH, Bedbrook A, Beghé B, Beji M, Ben Kheder A, Benet M, Bennoor KS, Bergmann KC, Berrissoul F, Bindslev Jensen C, Bleecker ER, Bonini S, Boner AL, Boulet LP, Brightling CE, Brozek JL, Bush A, Busse WW, Camargos PA, Canonica GW, Carr W, Cesario A, Chen YZ, Chiriac AM, Costa DJ, Cox L, Custovic A, Dahl R, Darsow U, Didi T, Dolen WK, Douagui H, Dubakiene R, El-Meziane A, Fonseca JA, Fokkens WJ, Fthenou E, Gamkrelidze A, Garcia-Aymerich J, Gerth van Wijk R, Gimeno-Santos E, Guerra S, Haahtela T, Haddad H, Hellings PW, Hellquist-Dahl B, Hohmann C, Howarth P, Hourihane JO, Humbert M, Jacquemin B, Just J, Kalayci O, Kaliner MA, Kauffmann F, Kerkhof M, Khayat G, Koffi N'Goran B, Kogevinas M, Koppelman GH, Kowalski ML, Kull I, Kuna P, Larenas D, Lavi I, Le LT, Lieberman P, Lipworth B, Mahboub B, Makela MJ, Martin F, Martinez FD, Marshall GD, Mazon A, Melen E, Meltzer EO, Mihaltan F, Mohammad Y, Mohammadi A, Momas I, Morais-Almeida M, Mullol J, Muraro A, Naclerio R, Nafti S, Namazova-Baranova L, Nawijn MC, Nyembue TD, Oddie S, O'Hehir RE, Okamoto Y, Orru MP, Ozdemir C, Ouedraogo GS, Palkonen S, Panzner P, Passalacqua G, Pawankar R, Pigearias B, Pin I, Pinart M, Pison C, Popov TA, Porta D, Postma DS, Price D, Rabe KF, Ratomaharo J, Reitamo S, Rezagui D, Ring J, Roberts R, Roca J, Rogala B, Romano A, Rosado-Pinto J, Ryan D, Sanchez-Borges M, Scadding GK, Sheikh A, Simons FE, Siroux V, Schmid-Grendelmeier PD, Smit HA, Sooronbaev T, Stein RT, Sterk PJ, Sunyer J, Terreehorst I, Toskala E, Tremblay Y, Valenta R, Valeyre D, Vandenplas O, van Weel C, Vassilaki M, Varraso R, Viegi G, Wang DY, Wickman M, Williams D, Wöhrl S, Wright J, Yorgancioglu A, Yusuf OM, Zar HJ, Zernotti ME, Zidarn M, Zhong N, and Zuberbier T

Subjects
Asthma therapy, Chronic Disease, Comorbidity, Dermatitis, Atopic complications, Humans, Hypersensitivity epidemiology, Rhinitis complications, Rhinitis epidemiology, Sinusitis complications, Sinusitis epidemiology, Urticaria complications, Urticaria epidemiology, Asthma physiopathology, Hypersensitivity complications, Practice Guidelines as Topic standards, Severity of Illness Index
Abstract

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies., (Copyright © 2012 S. Karger AG, Basel.)

Published
2012
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13. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

Author

Bousquet J, Anto J, Auffray C, Akdis M, Cambon-Thomsen A, Keil T, Haahtela T, Lambrecht BN, Postma DS, Sunyer J, Valenta R, Akdis CA, Annesi-Maesano I, Arno A, Bachert C, Ballester F, Basagana X, Baumgartner U, Bindslev-Jensen C, Brunekreef B, Carlsen KH, Chatzi L, Crameri R, Eveno E, Forastiere F, Garcia-Aymerich J, Guerra S, Hammad H, Heinrich J, Hirsch D, Jacquemin B, Kauffmann F, Kerkhof M, Kogevinas M, Koppelman GH, Kowalski ML, Lau S, Lodrup-Carlsen KC, Lopez-Botet M, Lotvall J, Lupinek C, Maier D, Makela MJ, Martinez FD, Mestres J, Momas I, Nawijn MC, Neubauer A, Oddie S, Palkonen S, Pin I, Pison C, Rancé F, Reitamo S, Rial-Sebbag E, Salapatas M, Siroux V, Smagghe D, Torrent M, Toskala E, van Cauwenberge P, van Oosterhout AJ, Varraso R, von Hertzen L, Wickman M, Wijmenga C, Worm M, Wright J, and Zuberbier T

Subjects
Cooperative Behavior, European Union, Humans, Hypersensitivity diagnosis, Hypersensitivity drug therapy, Hypersensitivity prevention & control, Medication Systems, Phenotype, Systems Biology, Hypersensitivity etiology
Abstract

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues., (© 2011 John Wiley & Sons A/S.)

Published
2011
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14. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort.

Author

Julvez J, Torrent M, Guxens M, Antó JM, Guerra S, and Sunyer J

Subjects
Child, Child, Preschool, Cohort Studies, Humans, Hypersensitivity immunology, Immunoglobulin E blood, Neuropsychological Tests, Skin Tests, Behavior, Child Development, Cognition, Hypersensitivity epidemiology, Hypersensitivity psychology, Immunoglobulin E immunology
Abstract

Background: Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy., Objective: To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later., Methods: A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used., Results: Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30-7.24) was associated with the lowest tertile (scorings < or =90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4., Conclusions: Neuropsychologic functioning and later atopy are negatively associated in preschool age children.

Published
2009
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15. On the association between date of birth and pollen sensitization: is age an effect modifier?

Author

Guerra S, Sherrill DL, Cottini M, Michetti G, and Allegra L

Subjects
Adolescent, Adult, Age Factors, Age of Onset, Female, Humans, Male, Middle Aged, Odds Ratio, Risk Factors, Allergens adverse effects, Asthma epidemiology, Asthma etiology, Birth Rate, Effect Modifier, Epidemiologic, Hypersensitivity epidemiology, Hypersensitivity etiology, Pollen adverse effects, Rhinitis, Allergic, Seasonal epidemiology, Rhinitis, Allergic, Seasonal etiology, Seasons
Abstract

An association between date of birth and development of allergy has been proposed by prior research. Yet, the presence of a dose-response relationship or any potential effect modification for this association has not been widely studied. The aims of our study were to investigate whether an association between birth during pollen season and symptomatic sensitization to pollens exists, whether this association is stronger for patients with high rather than low allergic reactivity to pollens, and whether this association is modified by the age of the patients. Among 3318 asthmatic and/or rhinitic outpatients, we selected 805 patients sensitized exclusively to pollens (78 with low reactivity [LR] and 727 with high reactivity [HR]) and 629 patients with negative skin-prick tests (SPT) (control group). The association between being born during pollen season (February-July) and each of the pollen reactivity levels was assessed by estimating the odds ratios (OR). HR pollinosis patients were more likely than SPT negative patients of being born in February-July (OR 1.38, 95% Confidence Intervals (CI) 1.11-1.71). The likelihood of having been born in pollen season significantly increased across the levels of reactivity to pollens (HR > LR > SPT negative). These findings were valid only among patients with an early onset of symptoms. Although the OR for being born in pollen season was 1.91 (95% CI 1.32-2.77) for HR pollinosis patients with onset of symptoms < or = 15 years, it was 1.13 (95% CI 0.87-1.48) for those with later onset of symptoms (test of homogeneity: p = 0.026). Our results suggest that the exposure to allergenic pollens in the first months of life increases the risk of developing clinically relevant sensitization to them, particularly in the first 15 years of life.

Published
2002

16. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Makela, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., Xu, C., dIRAS RA-2, Risk Assessment, Clinicum, Department of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J.M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D.S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B.N., Lodrup Carlsen, K.C., Koppelman, G.H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M.L., Maier, D., Melén, E., Palkonen, S., Smit, H.A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., Mceachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Subjects
multimorbidity, EUROPEAN INNOVATION PARTNERSHIP, humanos, Immunology, IGE SENSITIZATION, política de salud, Review, rhinitis, Inventions, Unión Europea, Hypersensitivity, Medicine and Health Sciences, Journal Article, Humans, Immunology and Allergy, ATOPIC-DERMATITIS, European Union, biología de sistemas, hipersensibilidad, inmunización, inmunoglobulina E, Asthma, Ige, Multimorbidity, Polysensitization, Rhinitis, BIRTH COHORT, IMMUNE-RESPONSES, Health Policy, Systems Biology, asthma, IgE, polysensitization, CHILDHOOD ASTHMA, invenciones, Immunoglobulin E, Prognosis, INTEGRATED CARE, pronóstico, rhiniti, CHRONIC RESPIRATORY-DISEASES, 3121 General medicine, internal medicine and other clinical medicine, Immunization, IMMUNOLOGICAL REACTIVITY, IMMUNOGLOBULIN-E
Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

17. Pooling birth cohorts in allergy and asthma: European union-funded initiatives-a MeDALL, CHICOS, ENRIECO, and GALEN joint paper: CHICOS study group ENRIECO study group GA2LEN study group

Author

Bousquet, Jean, Anto, Josep, Sunyer, Jordi, Nieuwenhuijsen, Mark, Vrijheid, Martine, Keil, Thomas, Akdis, M., Auffray, C., Postma, D. S., Valenta, R., Haahtela, T., Cambon-Thomsen, A., Lambrecht, B. N., Akdis, C. A., Annesi-Maesano, I., Arno, A., Bachert, C., Ballester, F., Basagana, X., Baumgartner, U., Bindslev-Jensen, C., Brunekreef, B., Chatzi, L., Eller, E., Forastiere, F., Garcia-Aymerich, J., Guerra, S., Gehring, U., Hammad, H., Heinrich, J., Hohmann, C., Kauffmann, F., Kerkhof, M., Kogevinas, M., Koppelman, G. H., Kowalski, M. L., Kull, I., Lau, S., Lodrup-Carlsen, K. C., Lupinek, C., Maier, D., Makela, M. J., Martinez, F. D., Momas, I., Nawijn, M. C., Neubauer, A., Oddie, S., Palkonen, S., Reitamo, S., Rial-Sebbag, E., Salapatas, M., Siroux, V., Smagghe, D., Smit, H. A., Torrent, M., Toskala, E., van Oosterhout, A. J. M., Varaso, R., von Hertzen, L., Wickman, M., Wijmenga, C., Zuberbier, T., Burney, P. G., Van Cauwenberge, P., Bonini, S., Fokkens, W. J., Kramer, U., Mullol, J., Nizankowska-Mogilnicka, E., Papadopoulos, N., Alm, B., Alm, J., Arshad, S. H., Bravi, F., Canonica, G. W., Custovic, A., Dubakiene, R., Fantini, M. P., Gjomarkaj, M., Halken, S., Host, A., Howarth, P., Kuehni, C., Lotvall, J., Mommers, M., Porta, D., Radon, K., Ring, J., Roberts, G., Schünemann, H. J., Simpson, A., Szczecklik, A., Thijs, C., Todo-Bom, A., Valovirta, E., van Steen, K., Von Berg, A., von Mutius, E., Wahn, U., Wennergren, G., Wijga, A. H., Zock, J. P., Duijts, L., Jaddoe, V., Lawlor, D., Lucas, P., Magnus, P., Merletti, F., Nybo Andersen, A. M., Raat, H., Stoltenberg, C., Casas, M., Bergström, A., Carmichael, A., Chen, C. -M., Cordier, S., Eggesbø, M., Fernández, M. F., Fernández-Somoano, A., Grazuleviciene, R., Karvonen, A. M., Koppen, G., Krämer, U., Kuehni, C. E., Majewska, R., Patelarou, E., Skaalum Petersen, M., Pierik, F. H., Polanska, K., Richiardi, L., Santos, A. C., Slama, R., Sram, R. J., Tischer, C., Toft, G., Trnovec, T., Vandentorren, S., Vardavas, C., Vrijkotte, T. G. M., Wilhelm, M., Bousquet, Jean, Anto, Josep, Sunyer, Jordi, Nieuwenhuijsen, Mark, Vrijheid, Martine, Keil, Thoma, Akdis, M., Auffray, C., Postma, D.S., Valenta, R., Haahtela, T., Cambon-Thomsen, A., Lambrecht, B.N., Akdis, C.A., Annesi-Maesano, I., Arno, A., Bachert, C., Ballester, F., Basagana, X., Baumgartner, U., Bindslev-Jensen, C., Brunekreef, B., Chatzi, L., Eller, E., Forastiere, F., Garcia-Aymerich, J., Guerra, S., Gehring, U., Hammad, H., Heinrich, J., Hohmann, C., Kauffmann, F., Kerkhof, M., Kogevinas, M., Koppelman, G.H., Kowalski, M.L., Kull, I., Lau, S., Lodrup-Carlsen, K.C., Lupinek, C., Maier, D., Makela, M.J., Martinez, F.D., Momas, I., Nawijn, M.C., Neubauer, A., Oddie, S., Palkonen, S., Reitamo, S., Rial-Sebbag, E., Salapatas, M., Siroux, V., Smagghe, D., Smit, H.A., Torrent, M., Toskala, E., van Oosterhout, A.J.M., Varaso, R., von Hertzen, L., Wickman, M., Wijmenga, C., Zuberbier, T., Burney, P.G., Van Cauwenberge, P., Bonini, S., Fokkens, W.J., Kramer, U., Mullol, J., Nizankowska-Mogilnicka, E., Papadopoulos, N., Alm, B., Alm, J., Arshad, S.H., Bravi, F., Canonica, G.W., Custovic, A., Dubakiene, R., Fantini, M.P., Gjomarkaj, M., Halken, S., Host, A., Howarth, P., Kuehni, C., Lotvall, J., Mommers, M., Porta, D., Radon, K., Ring, J., Roberts, G., Schünemann, H.J., Simpson, A., Szczecklik, A., Thijs, C., Todo-Bom, A., Valovirta, E., van Steen, K., Von Berg, A., von Mutius, E., Wahn, U., Wennergren, G., Wijga, A.H., Zock, J.P., Duijts, L., Jaddoe, V., Lawlor, D., Lucas, P., Magnus, P., Merletti, F., Nybo Andersen, A.M., Raat, H., Stoltenberg, C., Casas, M., Bergström, A., Carmichael, A., Chen, C.-M., Cordier, S., Eggesbø, M., Fernández, M.F., Fernández-Somoano, A., Grazuleviciene, R., Karvonen, A.M., Koppen, G., Krämer, U., Kuehni, C.E., Majewska, R., Patelarou, E., Skaalum Petersen, M., Pierik, F.H., Polanska, K., Richiardi, L., Santos, A.C., Slama, R., Sram, R.J., Tischer, C., Toft, G., Trnovec, T., Vandentorren, S., Vardavas, C., Vrijkotte, T.G.M., and Wilhelm, M.

Subjects
Allergy, Risk Factor, Immunology, CHICOS, Longitudinal Studie, Environmental Exposure, Asthma, Europe, MeDALL, ENRIECO, Hypersensitivity, Multicenter Studies as Topic, Immunology and Allergy, European Union, Cohort Studie, Birth cohort, Human
Abstract

Long-term birth cohort studies are essential to understanding the life course and childhood predictors of allergy and the complex interplay between genes and the environment (including lifestyle and socioeconomic determinants). Over 100 cohorts focusing on asthma and allergy have been initiated in the world over the past 30 years. Since 2004, several research initiatives funded under the EU Framework Program for Research and Technological Development FP6-FP7 have attempted to identify, compare, and evaluate pooling data from existing European birth cohorts (GA2LEN: Global Allergy and European Network, FP6; ENRIECO: Environmental Health Risks in European Birth Cohorts, FP7; CHICOS: Developing a Child Cohort Research Strategy for Europe, FP7; MeDALL: Mechanisms of the Development of ALLergy, FP7). However, there is a general lack of knowledge about these initiatives and their potentials. The aim of this paper is to review current and past EU-funded projects in order to make a summary of their goals and achievements and to suggest future research needs of these European birth cohort networks. © 2012 S. Karger AG, Basel.

Published
2013

18. Severe Chronic Allergic (and related) Diseases: a uniform approach- a MeDALL- GA(2)LEN-ARIA Position Paper

Author

WHO Collaborating Center for Asthma, Rhinitis, Bousquet, J, Anto, Jm, Demoly, P, Schünemann, Hj, Togias, A, Akdis, M, Auffray, C, Bachert, C, Bieber, T, Bousquet, Pj, Carlsen, Kh, Casale, Tb, Cruz, Aa, Keil, T, Lodrup Carlsen KC, Maurer, M, Ohta, K, Papadopoulos, Ng, Roman Rodriguez, M, Samolinski, B, Agache, I, Andrianarisoa, A, Ang, Cs, Annesi Maesano, I, Ballester, F, Baena Cagnani CE, Basagaña, X, Bateman, Ed, Bel, Eh, Bedbrook, A, Beghe', Bianca, Beji, M, Ben Kheder, A, Benet, M, Bennoor, Ks, Bergmann, Kc, Berrissoul, F, Bindslev Jensen, C, Bleecker, Er, Bonini, S, Boner, Al, Boulet, Lp, Brightling, Ce, Brozek, Jl, Bush, A, Busse, Ww, Camargos, Pa, Canonica, Gw, Carr, W, Cesario, A, Chen, Yz, Chiriac, Am, Costa, Dj, Cox, L, Custovic, A, Dahl, R, Darsow, U, Didi, T, Dolen, Wk, Douagui, H, Dubakiene, R, El Meziane, A, Fonseca, Ja, Fokkens, Wj, Fthenou, E, Gamkrelidze, A, Garcia Aymerich, J, Gerth van Wijk, R, Gimeno Santos, E, Guerra, S, Haahtela, T, Haddad, H, Hellings, Pw, Hellquist Dahl, B, Hohmann, C, Howarth, P, Hourihane, Jo, Humbert, M, Jacquemin, B, Just, J, Kalayci, O, Kaliner, Ma, Kauffmann, F, Kerkhof, M, Khayat, G, Koffi N'Goran, B, Kogevinas, M, Koppelman, Gh, Kowalski, Ml, Kull, I, Kuna, P, Larenas, D, Lavi, I, Le, Lt, Lieberman, P, Lipworth, B, Mahboub, B, Makela, Mj, Martin, F, Martinez, Fd, Marshall, Gd, Mazon, A, Melen, E, Meltzer, Eo, Mihaltan, F, Mohammad, Y, Mohammadi, A, Momas, I, Morais Almeida, M, Mullol, J, Muraro, A, Naclerio, R, Nafti, S, Namazova Baranova, L, Nawijn, Mc, Nyembue, Td, Oddie, S, O'Hehir, Re, Okamoto, Y, Orru, Mp, Ozdemir, C, Ouedraogo, Gs, Palkonen, S, Panzner, P, Passalacqua, G, Pawankar, R, Pigearias, B, Pin, I, Pinart, M, Pison, C, Popov, Ta, Porta, D, Postma, Ds, Price, D, Rabe, Kf, Ratomaharo, J, Reitamo, S, Rezagui, D, Ring, J, Roberts, R, Roca, J, Rogala, B, Romano, A, Rosado Pinto, J, Ryan, D, Sanchez Borges, M, Scadding, Gk, Sheikh, A, Simons, Fe, Siroux, V, Schmid Grendelmeier PD, Smit, Ha, Sooronbaev, T, Stein, Rt, Sterk, Pj, Sunyer, J, Terreehorst, I, Toskala, E, Tremblay, Y, Valenta, R, Valeyre, D, Vandenplas, O, van Weel, C, Vassilaki, M, Varraso, R, Viegi, G, Wang, Dy, Wickman, M, Williams, D, Wöhrl, S, Wright, J, Yorgancioglu, A, Yusuf, Om, Zar, Hj, Zernotti, Me, Zidarn, M, Zhong, N, Zuberbier, T., Beghe', B., Fthenou, E., Boudier, Anne, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), 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), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER Epidemiologia y Salud Publica, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), WHO Collaborating Center for Asthma and Rhinitis, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Génomique fonctionnelle et biologie systémique pour la santé, Institut des Sciences Biologiques du CNRS, Upper Airway Research Laboratory (URL), Ghent University Hospital, Department of Dermatology and Allergy, VU University Medical Center [Amsterdam], Department of Paediatrics, University of Oslo (UiO)-Oslo University Hospital [Oslo], Division of Allergy and Immunology, Department of Medicine, Creighton University, ProAR - FMB, Federal University of Bahia School of Medicine, Epidemiology and Health Economics, Instittute of Social Health-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Division of Respiratory Medicine and Allergology, Teikyo University School of Medicine, Allergy Department, 2nd Pediatric Clinic, Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Public Hospital Medical Service, Ministry of Health [Mozambique], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Public Health Research (CSISP), University of Valencia, Respiratory Medicine, Università degli studi di Genova = University of Genoa (UniGe)-School of Specialization, Faculty of Medicine, Catholic University, Health Sciences Faculty, University of Cape Town, Department of Pulmonology, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Centre, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Service de Pneumologie Allergologie, Hôpital La Rabta [Tunis], Service de Pneumologie, Hôpital Abderrahmen Mami, National Asthma Centre, National Institute of Diseases of the Chest and Hospital (NIDCH), Pneumologie / Anesthésie - réanimation / Oxygénothérapie, Hôpital AKS Phnom Penh-Hôpital Provincial de Siemreap, Department of Dermatology and Allergy Center, Odense University Hospital, Center for Genomics and Personalized Medicine, Wake Forest University, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Verona = University of Verona (UNIVR), Institut de cardiologie et de pneumologie, Université Laval [Québec] (ULaval)-Centre Hospitalier de Laval (CH Laval), Department of Respiratory Medicine and Thoracic Surgery, University of Leicester-Institute for Lung Health, Department of Paediatric Respiratory Medicine, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Department of Medicine, University of Wisconsin School of Medicine and Public Health, Department of Pediatrics, Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG)-Medical School, Allergy & Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe)-Department of Internal Medicine (DIMI), Allergy & Asthma Associates, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Deputy Scientific Director, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Department of Thoracic Surgery, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), National Cooperative Group of Pediatric Research on Asthma, Asthma Clinic and Education Center of the Capital Institute of Pediatrics, Service des Premiers Soins, Université Montpellier 1 (UM1), Osteopathic College of Medicine, Nova Southeastern University (NSU), Respiratory Research Group, University of Manchester [Manchester]-School of Translational Medicine, Department of Respiratory Diseases, Aarhus University Hospital, Department of Dermatology and Allergy Biederstein, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service de pneumologie, Centre hospitalier de la région d'Annecy, Service de pneumo-allergologie, Centre Hospitalo-Universitaire de Béni-Messous, Allergy Centre, Vilnius University Antakalnis Hospital, Société Marocaine des Maladies Respiratoires, Centre of Respiratory Diseases and Allergy-Centre commercial Nadia, Allergy Division, Hospital S. João-Centre for Research in Health Technologies and Information Systems (CINTESIS)-Biostatistics and Medical Informatics Department-Porto University Medical School, Department of Otorhinolaryngology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Social Medicine, University of Crete [Heraklion] (UOC)-Faculty of Medicine, Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Section of Allergology, Erasmus Medical Centre, Epidemiology and Biostatistics Division, University of Arizona-Associate Research Scientist, Respiratory Sciences-Arizona Respiratory Center, Helsinki University Hospital-Skin and Allergy Hospital, Centre Hospitalier de Bigorre [Tarbes]-Association Franco-Libanaise de Pneumologie (AFLP), Department of Otorhinolaryngology, Head, and Neck Surgery, University Hospital Leuven, Engineering and the Environment, University of Southampton, Paediatrics and Child Health, University College Cork (UCC), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pediatric Allergy and Asthma Unit, Ihsan Dogramaci Children's Hospital-Hacettepe University School of Medicine, Institute for Asthma and Allergy, George Washington University Medical School, Department of Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth (USJ)-Faculté de Médecine-Hôtel-Dieu de France, Service des Maladies Respiratoires, CHU de Cocody-UFR des Sciences Médicales, Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Clinical Immunology and Allergy, Medical University of Łódź (MUL)-Faculty ot Medicine, Centre for Allergy Research, Karolinska Institutet [Stockholm], Department of Clinical Science and Education, Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Hospital Medica Sur, Physiology Department, University of Medicine and Pharmacy, Division of Allergy Immunology, Department of Medicine-The University of Tennessee Health Science Center [Memphis] (UTHSC), university of dundee asthma - allergic rhinitis - COPD - beta-2-adrenoceptor, University of Dundee, Pulmonary and allergy unit, American University of Sharjah-Rashid Hospital-Dubai Health Authority (DHA), Association Franco-Vietnamienne de Pneumologie (AFVP), Centre Hospitalier de Compiègne (CHC), Arizona Respiratory Center, Department of Medicine, Clinical Immunology and Allergy, University of Mississippi Medical Center (UMMC), Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Allergy & Asthma Medical Group & Research Center, University of California [San Diego] (UC San Diego), Pneumology Department, Marius Nasta Institute of Pneumology, Department of Internal Medicine, Tishreen University School of Medicine, Association Franco-Marocaine de Pathologie Thoracique (AFMAPATH), Collège National des Pneumologues Marocains, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Immunoallergy Department, Hospital CUF Descobertas, Rhinology Unit & Smell Clinic, Universitat de Barcelona (UB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Allergy Unit, Università degli Studi di Padova = University of Padua (Unipd)-Department of Paediatrics, Section of Otolaryngology-Head & Neck Surgery (OHNS), University of Chicago, Clinique des maladies respiratoires, centre hospitalo-universitaire Mustapha Pacha d'Alger (CHUMA), Scientific Center for Children's Health, Russian Academy of Medical Sciences (RAMS), Laboratory of Allergology and Pulmonary Diseases, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Department of Pathology and Medical Biology-GRIAC Research Institute, ENT Department, University of Kinshasa (UNIKIN), Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust-Bradford Institute for Health Research, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Chiba University Hospital, Asthme Rhinite allergique, Pharmacie, Division of Pediatric Allergy and Immunology, marmara university, Pédiatrie, Centre Hospitalier National Pédiatrique Charles de Gaulle (CHNP-CDG), European Federation of Allergy (EFA), Airways Diseases Patients' Associations, Department of Allergology and Clinical Immunology, Charles University [Prague] (CU)-Medical Faculty in Pilsen, Immunopharmacology, Nippon Medical School-Medical Research Council Clinical, Laboratoire du Sommeil et de l'Effort, Société de Pneumologie de Langue Française (SPLF)-Clinique St George, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinic of Allergy and Asthma, Medical University Sofia-Alexander's University Hospital, Regional Health Service - Lazio, Primary Care Respiratory Medicine, University of Aberdeen-Department of General Practice and Primary Care-General Practice Airways Group (GPIAG), Department of Pulmonary Medicine, Leiden University Medical Center (LUMC), Pneumalgia, Centre Hospitalier Regional-Espace Francophone de Pneumologie (EFP)-Société de Pneumologie de l'Océan Indien (SPOI), Association Franco-Algérienne de Pneumologie (AFAP), Espace Francophone de pneumologie de la SPLF, Department of Pneumology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic de Barcelona-Institut Clínic del Tórax (ICT)-CIBER de Enfermedades Respiratorias (CIBERES)-University of Barcelona, Allergology and Clinical Immunology, Medical University of Silesia (SUM)-Chair and Clinical Department of Internal Diseases, UCSC-Allergy Unit, Complesso Integrato Columbus-Department of Internal Medicine and Geriatrics, Hospital da Luz, Medical Centre, Woodbrook Medical Centre, Research Fellow, University of Aberdeen-Department of General Practice, Centro Médico Docente La Trinidad, Department of Pharmacology, University College of London [London] (UCL)-The Royal National Throat, Nose and Ear Hospital, Primary Care Research & Development, University of Edinburgh-Centre for Population Health Sciences, Section of Allergy & Clinical Immunology, University of Manitoba [Winnipeg]-Department of Pediatrics & Child Health, Allergy Unit - Department of Dermatology, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], National Centre of Cardiology and Internal Medicine, Ministry of Health Kyrgyz Republic, School of Medicine, Pontifícia Universidade Católica, Department of ENT and Pediatrics, Finnish Institute of Occupational Health, Department of Obstetrics and Gynaecology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Christian Doppler Laboratory for Allergy Research, Medizinische Universität Wien = Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Department of Chest Medicine, Mont-Godinne Hospital-Catholic University of Louvain de Mont-Godinne, Department of Primary and Community Care, Radboud University Medical Center [Nijmegen], Epidemiology Unit, National Research Council (CNR)-Institute of Biomedicine and Molecular Immunology (IBIM), Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Department of Otolaryngology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, GLP Analytical Facility, School of Pharmacy, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna (MUW), Celal Bayar University School of Medicine, Allergy and Asthma Clinics, The Allergy and Asthma Institute, Department of Paediatrics and Child Health, Respiratory and Allergic Diseases, University Clinic of Respiratory and Allergic Diseases Golnik, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases-Guangzhou Medical College, Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], In collaboration with the WHO Collaborating Center for Asthma and Rhinitis, University of Genoa (UNIGE)-School of Specialization, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, University of Verona (UNIVR), Medical School-Federal University of Minas Gerais, University of Genoa (UNIGE)-Department of Internal Medicine (DIMI), University of California [Irvine] (UCI), University of California-University of California, Catholic University Rome, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Hospitalier de Bigorre (Tarbes)-Association Franco-Libanaise de Pneumologie (AFLP), CUF-Descobertas Hospital, Universita degli Studi di Padova-Department of Paediatrics, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Centro Medico-Docente La Trinidad, 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), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]-Instittute of Social Health, Department of Internal Medicine (DIMI)-University of Genoa (UNIGE), Medical University of Silesia-Chair and Clinical Department of Internal Diseases, Dermatology, Internal Medicine, Immunology, Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Research in Environmental Epidemiology ( CREAL ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universitat Pompeu Fabra [Barcelona], WHO(OMS), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), National Institute of Allergy and Infectious Diseases [Bethesda], National Institutes of Health ( NIH ), Swiss Institute of Allergy and Asthma Research ( SIAF ), University of Zürich [Zürich] ( UZH ), Upper Airway Research Laboratory ( URL ), University Medical Center, University of Oslo ( UiO ) -Oslo University Hospital, Charite-Universitatsmedizin Berlin [Berlin]-Instittute of Social Health, Medical School-Charité - University Medicine Berlin, Medical University of Warsaw-Faculté de Pharmacie de Paris, Ministry of Health, Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Public Health Research ( CSISP ), University of Genoa ( UNIGE ) -School of Specialization, University of Amsterdam [Amsterdam] ( UvA ) -Academic Medical Centre, University of Southampton [Southampton]-School of Medicine, Hôpital La Rabta [Tunis), Wake Forest University Health Sciences, CNR, Rome, Italy and Department of Medicine-Second University of Naples, Università degli Studi di Verona, Université Laval-l'Hôpital Laval, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, University of Genoa ( UNIGE ) -Department of Internal Medicine (DIMI), Southern California Research, Université Montpellier 1 ( UM1 ), Nova Southeastern University, Technische Universität München [München] ( TUM ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), University of Crete ( UOC ) -Faculty of Medicine, University of Southampton [Southampton], UUniversity College Cork - National University of Ireland, Cork (UCC), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], University of Groningen [Groningen]-University Medical Center Groningen-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth ( USJ ) -Faculté de Médecine-Hôtel-Dieu de France, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Medical University of Łódź ( MUL ) -Faculty ot Medicine, Medical University of Łódź ( MUL ) -Barlicki University Hospital, Department of Medicine-University of Tennessee College for Medicine, Association Franco-Vietnamienne de Pneumologie ( AFVP ), University of Mississippi Medical Center, University of California [San Diego] ( UC San Diego ), Association Franco-Marocaine de Pathologie Thoracique ( AFMAPATH ), Epidémiologie Environnementale : Impact Sanitaire des Pollutions ( EA 4064 ), Université Paris Descartes - Paris 5 ( UPD5 ), Universitat de Barcelona ( UB ) -Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Section of Otolaryngology-Head & Neck Surgery ( OHNS ), University of Groningen [Groningen]-University Medical Center Groningen-Department of Pathology and Medical Biology-GRIAC Research Institute, University Hospital of Kinshasa, European Federation of Allergy ( EFA ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Bioenergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of General Practice and Primary Care-General Practice Airways Group (GPIAG)-University of Aberdeen, Association Franco-Algérienne de Pneumologie ( AFAP ), Department of General Practice-University of Aberdeen, University College of London [London] ( UCL ) -The Royal National Throat, Nose and Ear Hospital, University Medical Center Utrecht, Faculty of Medicine-Laval University [Québec], Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases ( DIAID ), Secretary General of the Global Allergy and Asthma European Network ( GA2LEN ), Network of Excellence, Charité - Universitätsmedizin Berlin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Universiteit Leiden-Universiteit Leiden, and Medizinische Universität Wien = Medical University of Vienna

Subjects
MESH: Asthma, severity, MESH: Comorbidity, Comorbidity, Severity of Illness Index, urticaria, MESH : Chronic Disease, MESH: Practice Guidelines as Topic, MESH : Dermatitis, Atopic, MESH: Urticaria, risk, 216-31 [Rhinitis, atopy, allergen Int Arch Allergy Immunol. 2012,158(3)], atopic dermatitis, MESH : Rhinitis, MESH: Rhinitis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Effective primary care and public health [NCEBP 7], Immunoglobulin E - Asthma - Rhinitis - Rhinosinusitis - Urticaria - Atopic dermatitis, MESH : Practice Guidelines as Topic, Practice Guidelines as Topic, MESH : Comorbidity, MESH : Severity of Illness Index, IgE, MESH: Sinusitis, MESH : Urticaria, MESH: Hypersensitivity, macromolecular substances, MESH : Asthma, Dermatitis, Atopic, rhinitis, SDG 3 - Good Health and Well-being, MESH: Dermatitis, Atopic, MESH: Severity of Illness Index, Hypersensitivity, Humans, Sinusitis, rhinosinusitis, MESH : Hypersensitivity, MESH: Humans, MESH: Chronic Disease, MESH : Humans, Asthma, Atopic dermatitis, Immunoglobulin E, Rhinitis, Rhinosinusitis, Urticaria, asthma, allergy, MESH : Sinusitis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, control
Abstract

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies. Copyright (C) 2012 S. Karger AG, Basel

Published
2012

19. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine

Author

Bousquet, J., Anto, J., Auffray, C., Akdis, M., Cambon-Thomsen, A., Keil, T., Haahtela, T., Lambrecht, B. N., Postma, D. S., Sunyer, J., Valenta, R., Akdis, C. A., Annesi-Maesano, Isabella, Arno, A., Bachert, C., Ballester, F., Basagana, X., Baumgartner, U., Bindslev-Jensen, C., Brunekreef, B., Carlsen, K. H., Chatzi, L., Crameri, R., Eveno, E., Forastiere, F., Garcia-Aymerich, J., Guerra, S., Hammad, H., Heinrich, J., Hirsch, D., Jacquemin, B., Kauffmann, F., Kerkhof, M., Kogevinas, M., Koppelman, G. H., Kowalski, M. L., Lau, S., Lodrup-Carlsen, K. C., Lopez-Botet, M., Lotvall, J., Lupinek, C., Maier, D., Makela, M. J., Martinez, F. D., Mestres, J., Momas, I., Nawijn, M. C., Neubauer, A., Oddie, S., Palkonen, S., Pin, I., Pison, C., Rancé, F., Reitamo, S., Rial-Sebbag, E., Salapatas, M., Siroux, V., Smagghe, D., Torrent, M., Toskala, E., van Cauwenberge, P., van Oosterhout, A. J. M., Varraso, R., von Hertzen, L., Wickman, M., Wijmenga, C., Worm, M., Wright, J., Zuberbier, T., University of Zurich, Bousquet, J, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département des Accélérateurs, de Cryogénie et de Magnétisme (ex SACM) (DACM), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Environmental systems research, Osnabrück University, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Public Hospital Medical Service, Ministry of Health [Mozambique], Bousquet J, Anto J, R Valenta, CA Akdis, Annesi-Maesano I, Arno A, C Bachert, Ballester F, Basagana X, U Baumgartner, Jensen C Bindslev, B Brunekreef, C Auffray, KH Carlsen, L Chatzi, R Crameri, E Eveno, Forastière F, Garcia-Aymerich J, S Guerra, H Hammad, Heinrich J, D Hirsch, Akdis M, Jacquemin B, Kauffmann F, M Kerkhof, M Kogevinas, GH Koppelman, Kowalski ML, S Lau, KC-Carlsen Lødrup, M Botet Lopez, Lotvall J, Cambon-Thomsen A, C Lupinek, Maier D, Makela MJ, FD Martinez, Mestres J, Momas I, MC Nawijn, Neubauer A, S Oddie, S Palkonen, T Keil, Pin I, C Pison, Rancé F, S Reitamo, E-Sebbag Rial, M Salapatas, V Siroux, Smagghe D, M Torrent, E Toskala, T Haahtela, P Van Cauwenberge, Oosterhout van AJ, R Varraso, von Hertzen L, M Wickman, C Wijmenga, M Worm, Wright J, T Zuberbier ., BN Lambrecht, DS Postma, Sunyer J, and Universität Osnabrück - Osnabrück University

Subjects
2403 Immunology, Phenotype, 10183 Swiss Institute of Allergy and Asthma Research, Systems Biology, 2723 Immunology and Allergy, Hypersensitivity, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 610 Medicine & health, European Union, allergy, early diagnosis, epigenetics, framework programme 7, IgE, mechanisms, mechanisms of the development of allergy, prevention, proteomics, systems medicine, transcriptomics, Cooperative Behavior, Medication Systems
Abstract

International audience; The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

Published
2011

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