Background Epithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood. Methods We used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes. We objectively confirmed these findings in epithelial brushings and primary asthmatic epithelial cells cultured in different biological contexts. Results We found a striking suppression of epithelial differentiation in asthma, overrepresented by insufficiency in insulin and Notch signaling, but with the absence of conventional EMT markers. We identified EFNB2, FGFR1, FGFR2, INSR, IRS2, NOTCH2, TLE1, and NTRK2 as novel markers central to dysregulation of epithelial-mesenchymal signaling, but surprisingly overlooked in asthma research. We found that this “core” signature of asthma is shared by mild, moderate, and severe forms of disease, progressing with severity. Loss of epithelial differentiation induced by insulin deprivation in normal human bronchial epithelial cells cultured in organotypic conditions closely approximated gene expression in asthmatic epithelial brushings. Conclusions The comparative analysis of publically available transcriptomes demonstrated that epithelial barrier dysfunction in asthma is characterized by persistent underlying de-differentiation program with complex etiology. The lasting alteration of the asthmatic epithelial cell transcriptome implicates regulation involving metabolism and epigenetics, beyond EMT driven by injury and repair in chronic inflammation.

YouTube videos of asthma were frequently viewed but were a poor source of accurate health care information. Videos by asthma health care providers were rated highest in quality. The allergy/immunology community has a clear opportunity to enhance the value of educational material on YouTube.

YouTube videos on food allergy frequently recommend controversial diagnostics and commonly depict non-IgE-mediated reactions. There is a need for high-quality, evidence-based, educational videos on food allergy.

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Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.