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

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.

Risk of adult‐onset asthma increases with the number of allergic multimorbidities and decreases with age

“…The strong association between allergic multimorbidity and adult‐onset asthma observed in this study extends to adulthood observations well demonstrated in children. The association between asthma and allergic multimorbidity, including rhinitis, conjunctivitis, and dermatitis, is well described in children . Causal network analysis in school‐aged children has shown that allergen sensitization, allergic inflammation, environmental tobacco smoke exposure, pulmonary physiology, and rhinitis severity explained over half of the variance in asthma severity .…”

“…Asthma, a common noncommunicable disease, is a major public health issue, with over 300 million people affected worldwide . In children, several cohort studies showed that allergic diseases were associated with increased risk of asthma . A study of German children showed that asthma occurs in both sexes more frequently with coexisting allergies than as a single entity .…”

Unsupervised trajectories of respiratory/allergic symptoms throughout childhood in the PARIS cohort

“…Few studies have used multidimensional approaches to characterize the co‐evolution over childhood of a large set of respiratory/allergy symptoms; most studies have been limited to one dimension, either longitudinal latent class analysis dealing with a single symptom or cross‐sectional cluster analysis dealing with several outcomes . As new insights on multimorbidity are needed, studying co‐occurrence of allergic diseases is crucial.…”

Multimorbidity in Asthma, Allergic Conditions and COPD Increase Disease Severity, Drug Use and Costs: The Finnish Pharmacy Survey

“…Shared risk gene variants have been suggested in asthma, allergic rhinitis, and atopic eczema [21]. Monosensitization and polysensitization have been proposed as different phenotypes, especially the latter increasing the risk of multimorbidity [22, 23]. However, in a longitudinal cohort of children, the non-IgE conditions increased the risk of multimorbidity [3].…”