Background: Allergy-related diseases are a public health issue but knowledge on

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.

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.

Specific IgE is strongly associated with eczema and allergic multimorbidity throughout childhood and with asthma and rhinitis from age 4 years. However, 23% of the children with IgE sensitization do not develop any disease in childhood.

More preadolescent girls than boys had eczema. FLG mutations did not influence eczema severity in our population-based cohort. Prevalence of rhinitis and asthma was associated with eczema severity, with the highest prevalence among boys with moderate-to-severe eczema.

In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

Background: Up to half of the population in high-income countries has allergen-specific IgE antibodies. However, data regarding sex differences of IgE-sensitization from childhood to adulthood is limited. Objective: To explore IgE-sensitization to common foods and airborne allergens in relation to sex over time in a population-based cohort followed up to young adulthood. Methods: The Swedish population-based birth cohort BAMSE includes 4089 subjects who have been followed regularly with questionnaires and clinical investigations. A recent 24-year follow-up included 3069 participants (75%). Sera collected at 4, 8, 16 and 24 years were analyzed for IgE-antibodies to 14 common foods and airborne allergens. Results: At 24 years sensitization to foods had decreased compared to previous follow-ups affecting 8.4%, while sensitization to airborne allergens was more common, affecting 42.2%. Male sex was associated with IgE-sensitization to airborne allergens at all ages (overall OR: 1.68, 95% CI 1.46-1.94) while there was no statistically significant association between sex and sensitization to food allergens (overall OR: 1.10, 95% CI 0.93-1.32). Levels of allergen-specific IgE did not differ significantly between males and females for any of the tested foods or airborne allergens at any age, following adjustment for multiple comparisons. Conclusion: IgE-sensitization to airborne allergens increases with age up to young adulthood, whereas sensitization to food allergens seems to level off. Male sex is strongly associated with IgE-sensitization to airborne allergens from early childhood up to young adulthood. In contrast, there is little evidence for associations between sex and IgEsensitization to foods.

Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases.