Our results confirm the good prognosis for the dermatitis and the increased risk of developing asthma and allergic rhinitis. Development of other allergic symptoms or sensitization was associated with the following factors: a family history of eczema, age at onset of eczema and its severity, early adverse reactions to foods, and proneness to infections.

Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onset mainly in early childhood It is commonly the initial clinical manifestation of allergic disease, often preceding the onset of respiratory allergies. Along with asthma and allergic rhinitis, atopic dermatitis is an important manifestation of atopy that is characterized by the formation of allergy antibodies (IgE) to environmental allergens. In the developed countries, the prevalence of atopic dermatitis is approximately 15%, with a steady increase over the past decades. Genetic and environmental factors interact to determine disease susceptibility and expression, and twin studies indicate that the genetic contribution is substantial. To identify susceptibility loci for atopic dermatitis, we ascertained 199 families with at least two affected siblings based on established diagnostic criteria. A genome-wide linkage study revealed highly significant evidence for linkage on chromosome 3q21 (Zall=4.31, P= 8.42 10(-6)). Moreover, this locus provided significant evidence for linkage of allergic sensitization under the assumption of paternal imprinting (hlod=3.71,alpha=44%), further supporting the presence of an atopy gene in this region. Our findings indicate that distinct genetic factors contribute to susceptibility to atopic dermatitis and that the study of this disease opens new avenues to dissect the genetics of atopy.

Activation of the RAS-RAF-MEK-ERK signaling pathway is implicated in driving the initiation and progression of multiple cancers. Several inhibitors targeting the RAS-MAPK pathway are clinically approved as single- or polyagent therapies for patients with specific types of cancer. One example is the MEK inhibitor trametinib, which is included as a rational polytherapy strategy for treating EML4-ALK-positive, EGFR-activated, or KRAS-mutant lung cancers and neuroblastomas that also contain activating mutations in the RAS-MAPK pathway. In addition, in neuroblastoma, a heterogeneous disease, relapse cases display an increased rate of mutations in ,, and , leading to increased activation of RAS-MAPK signaling. Co-targeting ALK and the RAS-MAPK pathway is an attractive option, because monotherapies have not yet produced effective results in ALK-addicted neuroblastoma patients. We evaluated the response of neuroblastoma cell lines to MEK-ERK pathway inhibition by trametinib. In contrast to RAS-MAPK pathway-mutated neuroblastoma cell lines, ALK-addicted neuroblastoma cells treated with trametinib showed increased activation (inferred by phosphorylation) of the kinases AKT and ERK5. This feedback response was mediated by the mammalian target of rapamycin complex 2-associated protein SIN1, resulting in increased survival and proliferation that depended on AKT signaling. In xenografts in mice, trametinib inhibited the growth of EML4-ALK-positive non-small cell lung cancer and RAS-mutant neuroblastoma but not ALK-addicted neuroblastoma. Thus, our results advise against the seemingly rational option of using MEK inhibitors to treat ALK-addicted neuroblastoma.

Twenty children with severe asthma using continual oral beta 2 agonists were randomized equally into either a behavioral intervention group or a control group. The behavioral intervention consisted of: symptom discrimination of asthma signals, self-management techniques of breathlessness, and contingency management of asthma-related behavior. The purpose of the study was to evaluate the effects of the behavioral treatment when superimposed on a regular medical treatment. The design consisted of a four-week baseline period, a four-week intervention period, and a four-week follow-up period. Results showed that the group receiving the behavioral intervention significantly reduced their use of beta 2 agonist spray doses and days of school absenteeism without increasing the number of asthma symptoms compared with the control group. It was concluded that children with severe asthma may benefit substantially from a behavioral program in addition to their regular medical treatment.

Previously we investigated the eczema prognosis and the risk of developing allergic asthma and rhinitis in a cohort of 94 children with atopic dermatitis. In this second study on the same cohort we address the development of sensitization to foods and airborne allergens, risk factors and, the question whether children with atopic dermatitis who will not become sensitized can be recognized early. Children with atopic dermatitis were followed up regularly from infancy or early childhood to 7 years of age with clinical examination and blood sampling. After age 3, skin prick tests with inhalation allergens were performed yearly. In most children both clinical allergy and sensitization to egg and milk were transient but those to peanut were persistent. Eighty per cent of the children became sensitized to airborne allergens and 75% of them noticed symptoms when exposed. Heredity for atopy and eczema, sensitization to hen's egg, and early onset of eczema entailed an increased risk of becoming sensitized. Children never sensitized had late onset of eczema and less heredity for atopic disease but did not differ in other respects from the sensitized children.