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It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and nonlesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease‐related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations—an "AD‐like microbiome," but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation. [ABSTRACT FROM AUTHOR]

The H4R is highly expressed on eosinophils from AD patients and IL-4 upregulates expression and function via the JAK/STAT pathway Taken together, we show for the first time that the H SB 4 sb R mRNA is upregulated via IL-4 and IL-13 in human eosinophils and that IL-4 receptor-induced upregulation is mediated via the JAK/STAT pathway. Moreover, we demonstrated that eosinophils from the circulation of AD patients showed a significantly higher basal expression of H SB 4 sb R and a higher upregulation after IL-4 stimulation compared to eosinophils from healthy subjects or psoriasis patients (Figure 1J-L). [Extracted from the article]

The allergic phenotype manifests itself in a spectrum of troublesome to life‐threatening diseases, from seasonal hay fever, through the food allergies, atopic eczema, asthma, to anaphylaxis. Allergy, that is an overreaction to allergen in hypersensitive individuals, results from the production of IgE, mast cell and basophil sensitisation and degranulation, requiring a range of medications to manage the conditions. Yet it is highly likely that allergy evolved for a purpose and that allergic diseases are accidental consequences of an insufficiently regulated immune response. This article presents a viewpoint from which to restore the immunological reputation of the allergic phenotype. We consider the evolutionary origins of potential allergens, toxins and parasites, and how they might have influenced early‐mammal species in existence when IgE first developed. We conclude that the allergic phenotype has likely saved the lives of many more mammals than have ever died from allergy, so justifying the positive role of IgE in our evolution. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease in children, with 30% of all those diagnosed developing chronic or relapsing disease by adolescence. Such disease persistence cannot yet be predicted. The aim of the present study was to predict the natural course of AD using clinical parameters and serum proteins. Methods: Sera of 144 children with AD (age 0‐3 years) were analyzed for IgE and 33 cytokines, chemokines, and growth factors. Patient disease course until the age of 7 years was assessed retrospectively. Unsupervised k‐means clustering was performed to define disease endotypes. Identified factors associated with AD persistence at the age of 7 years were validated in children with AD in an independent cohort (LISA Munich; n = 168). Logistic regression and XGBoosting methods followed by cross‐validation were applied to predict individual disease outcomes. Results: Three distinct endotypes were found in infancy, characterized by a unique inflammatory signature. Factors associated with disease persistence were disease score (SCORAD), involvement of the limbs, flexural lesion distribution at the age of 3 years, allergic comorbidities, and disease exacerbation by the trigger factors stress, pollen exposure, and change in weather. Persistence was predicted with a sensitivity of 81.8% and a specificity of 82.4%. Factors with a high impact on the prediction of persistence were SCORAD at the age of 3 years, trigger factors, and low VEGF serum levels. Conclusion: Atopic dermatitis in infancy comprises three immunological endotypes. Disease persistence can be predicted using serum cytokines and clinical variables. [ABSTRACT FROM AUTHOR]

Keywords: allergic conjunctivitis; microbiome; ocular surface EN allergic conjunctivitis microbiome ocular surface 596 600 5 02/20/21 20210201 NES 210201 Allergic conjunctivitis (AC) is one of the most common ocular surface diseases that encompasses a spectrum of diseases featured by antigen-specific immunoglobulin E (IgE) and T helper type 2 (Th2) lymphocyte-mediated hypersensitivity responses.1 Among different types of AC, seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) manifest the classical type I hypersensitivity. I Malassezia i produces immunogenic proteins that elicit IgE and thus induce pro-inflammatory cytokines and auto-reactive T cells, which contributes to atopic dermatitis pathogenesis.3 Notably, SAC/PAC is dominated by IgE-mediated reactions in contrast to VKC. A, Genus compositions of healthy subjects (n = 48) and AC patients with SAC/PAC (n = 21) or VKC (n = 18). [Extracted from the article]

Keywords: allergy treament; asthma; atopic dermatitis; ENT (rhinitis; sinusitis; nasal polyps...); immunotherapy clinical EN allergy treament asthma atopic dermatitis ENT (rhinitis sinusitis nasal polyps...) immunotherapy clinical 593 596 4 02/20/21 20210201 NES 210201 Allergic diseases such as asthma, chronic rhinosinusitis (CRS), atopic dermatitis (AD), allergic rhinitis, and eosinophilic esophagitis (EoE) affect more than 30% of the population,1 with a dramatic increase2 and a lack of effective treatments for recurrent or adverse effects of corticosteroids and immunosuppressants.3,4 Dupilumab is a monoclonal antibody that targets the IL-4 receptor alpha subunit and inhibits IL-4/IL-13 signaling, thus downregulating type-2 inflammatory responses.5 Currently, dupilumab has proven effectiveness in patients with serious allergic diseases.6-8 However, the evidence on safety of dupilumab is insufficient in allergic diseases. A pooled analysis showed that the incidence of any serious TEAE was 223 of 4923 (4.53%) patients receiving dupilumab treatment and 139 of 2401 (5.79%) patients receiving placebo. The risk of any leading to permanent treatment discontinuation in patients receiving dupilumab treatment was similar to that in patients receiving placebo (RR = 0.78; 95% CI, 0.53-1.16; I P i = .23; I2 = 32.37%; Figure 1D). What's more, our result showed that dupilumab is associated with a lower risk of developing other allergic diseases, such as asthma or sinusitis, indicated that dupilumab can effectively prevent the occurrence of other allergic diseases in patients with allergic disease and that it plays a defensive and protective role against allergic diseases. [Extracted from the article]

Keywords: algorithm; allergy; atopic; atopic dermatitis; childhood; children; diagnosis; eczema; immune system; medical algorithm; pediatric EN algorithm allergy atopic atopic dermatitis childhood children diagnosis eczema immune system medical algorithm pediatric 403 406 4 01/09/21 20210101 NES 210101 Atopic dermatitis (AD, atopic eczema) is a chronic, relapsing, pruritic, noncommunicable inflammatory skin disease that affects children and adults.1 It almost always has its debut in early life;2,3 therefore, this medical algorithm focuses on diagnosis (part I) and therapy (part II4) of AD in early childhood, which is defined by UNESCO as "the period from birth to eight years old." ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. Algorithm, allergy, atopic, atopic dermatitis, childhood, children, diagnosis, eczema, immune system, medical algorithm, pediatric. [Extracted from the article]

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate‐to‐severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD −30,72; 95% CI −34,65% to −26,79%) and EASI‐75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD −7.29; 95% CI −8.23 to −6.35) and anxiety/depression (MD −3.08; 95% CI −4.41 to −1.75) and improves quality of life (MD −4.80; 95% CI −5.55 to −4.06). The efficacy for adolescents is similar. Dupilumab‐related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab‐related serious AE is uncertain. The incremental cost‐effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645). [ABSTRACT FROM AUTHOR]

Keywords: algorithm; atopic dermatitis; children; eczema; therapy EN algorithm atopic dermatitis children eczema therapy 407 410 4 01/09/21 20210101 NES 210101 The diagnostic work-up of atopic dermatitis (AD, atopic eczema) was discussed in part I.1 This part of the medical algorithm focuses on the therapy of AD in early childhood and is based on recent literature and international guidelines.2-4 The management of AD is mainly based on disease severity, which has already been discussed in part I. Basic therapy of the disturbed skin barrier is always necessary, that is, also for children that do not suffer from active lesions. Climate therapy at high altitude is beneficial for atopic dermatitis, probably due to UV exposure, avoidance of allergen exposure, and decreased stress.7 For severe AD, or for cases that do not respond well to topical therapy, wet wrap therapy can be initiated in inpatient or outpatient settings.8 Ultraviolet (UV) therapy is used reluctantly in early childhood due to the cumulative UV dosage, time necessary, and anxiety in the UV cabin. Given the special pace of innovation in AD treatment, the future is bright for young children with severe atopic dermatitis!. [Extracted from the article]

Background: Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early‐onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent‐onset, moderate‐to‐severe AD using tape strips. Methods: Sixteen tape strips were collected for RNA‐seq profiling from 19 infants/toddlers (<5 years old; lesional and nonlesional) with early‐onset moderate‐to‐severe AD (≤6 months) and 17 healthy controls. Results: We identified 1829 differentially expressed genes/DEGs in lesional AD and 662 DEGs in nonlesional AD, vs healthy skin (fold‐change ≥2, FDR <0.05), with 100% sample recovery. Both lesional and nonlesional skin showed significant dysregulations of Th2 (CCL17 and IL4R) and Th22/Th17 (IL36G, CCL20, and S100As)‐related genes, largely lacking significant Th1‐skewing. Significant down‐regulation of terminal differentiation (FLG and FLG2), lipid synthesis/metabolism (ELOVL3 and FA2H), and tight junction (CLDN8) genes were primarily seen in lesional AD. Significant negative correlations were identified between Th2 measures and epidermal barrier gene‐subsets and individual genes (FLG with IL‐4R and CCL17; r < −0.4, P <.05). Significant correlations were also identified between clinical measures (body surface area/BSA, pruritus ADQ, and transepidermal water loss/TEWL) with immune and barrier mRNAs in lesional and/or nonlesional AD (FLG/FLG2 with TEWL; r < −0.4, P <.05). Conclusion: RNA‐seq profiling using tape strips in early‐onset pediatric AD captures immune and barrier alterations in both lesional and nonlesional skin. Tape strips provide insight into disease pathomechanisms and cutaneous disease activity. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) patients are often colonized with Staphylococcus aureus, and staphylococcal biofilms have been reported on adult AD skin lesions. The commensal S epidermidis can antagonize S aureus, although its role in AD is unclear. We sought to characterize S aureus and S epidermidis colonization and biofilm propensity and determine their associations with AD severity, barrier function, and epidermal gene expression in the first US early‐life cohort of children with AD, the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH). Methods: The biofilm propensity of staphylococcal isolates was assessed by crystal violet assays. Gene expression of filaggrin and antimicrobial alarmins S100A8 and S100A9 was measured in keratinocyte RNA extracted from skin tape strips. Staphylococcal biofilms sampled from MPAACH skin were visualized using scanning electron microscopy. Results: Sixty‐two percent of staphylococcal isolates (sampled from 400 subjects) formed moderate/strong biofilms. Sixty‐eight percent of subjects co‐colonized with both staphylococcal species exhibited strains that formed cooperative mixed‐species biofilms. Scanning electron microscopy verified the presence of staphylococcal biofilms on the skin of MPAACH children. Staphylococcus aureus strains showing higher relative biofilm propensity compared with S epidermidis were associated with increased AD severity (P =.03) and increased lesional and nonlesional transepidermal water loss (P =.01, P =.03). Conclusions: Our data suggest a pathogenic role for S aureus biofilms in AD. We found that strain‐level variation in staphylococcal isolates governs the interactions between S epidermidis and S aureus and that the balance between these two species, and their biofilm propensity, has important implications for AD. [ABSTRACT FROM AUTHOR]

Background: Endothelin‐1 (EDN1) can evoke histamine‐independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL‐25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods: We analyzed the mite‐induced AD‐like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to nerve elongation and branching assays after EDN1 stimulation. Results: Topical application of bosentan significantly attenuated the development of mite‐induced AD‐like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation‐regulated chemokine in NC/Nga mice. Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose‐ and time‐dependent manner, bosentan treatment attenuated this. Conclusions: EDN1 plays a significant role in mite‐induced inflammation and itch. Topical bosentan is a potential protective candidate for AD. [ABSTRACT FROM AUTHOR]

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half‐life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long‐term follow‐up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half‐life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy. [ABSTRACT FROM AUTHOR]

Additionally, they performed basophil depletion experiments using an antibody against the murine basophil activation marker CD200R in wild-type mice, and diphtheria toxin (DT) in Bas-TRECK mice, which exclusively express the DT receptor on basophils. Keywords: allergic inflammation; atopic dermatitis; basophils; leukotriene C; neuroimmunology EN allergic inflammation atopic dermatitis basophils leukotriene C neuroimmunology 708 710 3 02/01/22 20220201 NES 220201 Abbreviations AD atopic dermatitis CCL C-C chemokine ligand CCR C-C chemokine receptor CysLTR Cysteinyl leukotriene receptor DT diphtheria toxin HR histamine receptor LT leukotriene MCs mast cells OVA ovalbumin Allergic inflammation is often the result of a dysregulated Th2 immune response, IgE production, and the release of allergic mediators such as histamine or leukotrienes (LTs) by basophils and mast cells (MCs). Local inflammation enables a basophil-neuronal circuITCH in atopic dermatitis. [Extracted from the article]

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long‐lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker‐driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Atopic eczema (atopic dermatitis, AD) is characterized by disrupted skin barrier associated with elevated skin pH and skin microbiome dysbiosis, due to high Staphylococcus aureus loads, especially during flares. Since S aureus shows optimal growth at neutral pH, we investigated the longitudinal interplay between these factors and AD severity in a pilot study. Method: Emollient (with either basic pH 8.5 or pH 5.5) was applied double‐blinded twice daily to 6 AD patients and 6 healthy (HE) controls for 8 weeks. Weekly, skin swabs for microbiome analysis (deep sequencing) were taken, AD severity was assessed, and skin physiology (pH, hydration, transepidermal water loss) was measured. Results: Physiological, microbiome, and clinical results were not robustly related to the pH of applied emollient. In contrast to longitudinally stable microbiome in HE, S aureus frequency significantly increased in AD over 8 weeks. High S aureus abundance was associated with skin pH 5.7‐6.2. High baseline S aureus frequency predicted both increase in S aureus and in AD severity (EASI and local SCORAD) after 8 weeks. Conclusion: Skin pH is tightly regulated by intrinsic factors and limits the abundance of S aureus. High baseline S aureus abundance in turn predicts an increase in AD severity over the study period. This underlines the importance and potential of sustained intervention regarding the skin pH and urges for larger studies linking skin pH and skin S aureus abundance to understand driving factors of disease progression. [ABSTRACT FROM AUTHOR]

Background: Patients with atopic dermatitis (AD) often show the infiltration of basophils in the affected skin. Because basophils represent only a minor fraction among cellular infiltrates in the skin lesion, the functional significance of skin‐infiltrating basophils in AD pathogenesis remains ill‐defined. In this study, we aimed to clarify the role of basophils and their effector molecules triggering skin inflammation in oxazolone (OX)‐induced murine model of AD. Methods: A panel of mouse strains were sensitized and repeatedly challenged with topical applications of OX to induce AD‐like skin inflammation. Both local and systemic Th2 immune responses were analyzed. Results: Basophils progressively accumulated in the skin lesion but barely in draining lymph nodes (LNs). When basophils were depleted during the elicitation phase, skin inflammation was ameliorated while Th2 cell differentiation in draining LNs remained intact. The expression of IL‐4 was highly upregulated in the affected skin, and basophils turned out to be the major producers of IL‐4 among cellular infiltrates, suggesting the involvement of basophil‐derived IL‐4 in the Th2 skin inflammation. Indeed, basophil‐specific IL‐4‐deficient mice displayed attenuated skin inflammation with a marked reduction of IL‐4 in the skin lesion, even though cutaneous basophil infiltration and serum levels of IgE remained intact. Conclusions: Skin‐infiltrating basophils promoted OX‐induced AD‐like skin inflammation through their local production of IL‐4, rather than the induction of Th2 cell differentiation in draining LNs. This study suggests that the selective targeting of basophils could be a beneficial strategy in the treatment of a certain type of AD. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is an anti‐IL‐4Rα antibody used in the treatment of patients with moderate‐to‐severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. Methods: This multicentric, prospective, observational, real‐life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16 weeks. Safety was also assessed. Results: We enrolled 123 patients with msAD. Between baseline and 16 weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient‐Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n = 41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five‐item Asthma Control Questionnaire scores) and disease‐related QoL (measured using the Asthma QoL Questionnaire scores). Thirty‐five patients (28.5%) developed conjunctivitis during the study period. Conclusion: These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD. [ABSTRACT FROM AUTHOR]

Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. In humans, they reported that a mixture of minimal-length peptides, representing the major T-cell epitopes of allergen, is sufficient to induce specific tolerance in T cells and successful allergen-specific immunotherapy. [Extracted from the article]

Keywords: atopic dermatitis; emollients; food allergens EN atopic dermatitis emollients food allergens 1121 1122 2 04/04/23 20230401 NES 230401 We read, with great interest, Ní Chaoimh et al.'s[1] article in the August 2022 issue of the I Allergy i . However, oat-derived ingredients in personal care products can cause immediate- and delayed-type hypersensitivity reactions.[5] It was shown that children with AD have a high oat sensitization, oat atopy patch tests, and skin-prick tests were positive in 14.6% and 19.2% of cases, respectively.[6] In addition, an association between oat sensitization and the repeated applications of oat-containing skin care products was found. When they are dried, extracted, and filtered, protein-free extracts, which are active ingredients in emollient-plus products, are produced.[8] We want to highlight the importance of choosing bland and food allergen-free skin care products. [Extracted from the article]

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual‐allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL‐33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome. [ABSTRACT FROM AUTHOR]

Background: The allergy preventive effects of gut immune modulation by bacterial compounds are still not fully understood. Objective: We sought to evaluate the effect of bacterial lysate applied orally from the second until seventh months of life on the prevalence of allergic diseases at school age. Methods: In a randomized, placebo‐controlled trial, 606 newborns with at least one allergic parent received orally a bacterial lysate consisting of heat‐killed Gram‐negative Escherichia coli Symbio and Gram‐positive Enterococcus faecalis Symbio or placebo from week 5 until the end of month 7. A total of 402 children were followed until school age (6‐11 years) for the assessment of current atopic dermatitis (AD), allergic rhinitis (AR), asthma and sensitization against aeroallergens. Results: AD was diagnosed in 11.0% (22/200) of children in the active and in 10.4% (21/202) of children in the placebo group. AR was diagnosed in 35% (70/200) of children in the active and in 38.1% (77/202) children in the placebo group. Asthma was diagnosed in 9% (18/199) of children in the active and in 6.6% (13/197) of children in the placebo group. Sensitization occurred in 46.5% (66/142) of participants in the active and 51.7% (76/147) in the placebo group. Conclusion: An oral bacterial lysate of heat‐killed Gram‐negative Escherichia coli and Gram‐positive Enterococcus faecalis applied during the first 7 months of life did not influence the development of AD, asthma and AR at school age. [ABSTRACT FROM AUTHOR]

Keywords: atopic dermatitis; atopy; food sensitization; live biotherapeutic product; microbiota EN atopic dermatitis atopy food sensitization live biotherapeutic product microbiota 1 4 4 07/29/20 20200801 NES 200801 Abbreviations LBP live biotherapeutic product rDNA ribosomal deoxyribonucleic acid SCFA short-chain fatty acid Forty percent of the world's population is sensitized to at least one environmental allergen, and atopic diseases such as asthma, atopic dermatitis, and food allergy are among the most frequent health challenges faced by children today. Specifically, increased bacterial diversity (as quantified by the Shannon -diversity index) was associated with protection against allergic sensitization (atopy), wheeze, AW, FS, and AD (Figure 1A and Figure E4). [Extracted from the article]

There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)‐25, IL‐33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL‐4, IL‐5, IL‐9, and IL‐13. IL‐4 and IL‐13 activate B cells to class‐switch to IgE and also play a role in T‐cell and eosinophil migration to allergic inflammatory tissues. IL‐13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL‐4 and IL‐13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL‐5 acts on activation, recruitment, and survival of eosinophils. IL‐9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL‐5 and its receptor, and IL‐4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and nonresponder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T‐cell maturation, regulatory T‐cell development, and T‐cell signaling, such as Omenn syndrome, severe combined immune deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome, and DOCK8, STAT3, and CARD11 deficiencies, help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and AD. [ABSTRACT FROM AUTHOR]

Keywords: asthma; atopic dermatitis; bioinformatics; food allergy; "omics" and systems biology EN asthma atopic dermatitis bioinformatics food allergy "omics" and systems biology 1789 1793 5 07/14/20 20200701 NES 200701 Driven mostly by the recent explosion of high-throughput technologies including sequencing, genotyping, and big data analytics, a vast amount of multi-omics and functional annotation data are accumulating for allergic diseases. GLO:1X5/01jul20:all14219-fig-0002.jpg PHOTO (COLOR): Gene word cloud summary of the five major allergic diseases (asthma, atopic dermatitis, food allergy, allergic rhinitis, and eosinophilic esophagitis). Food allergy and eosinophilic esophagitis share 100% genes with asthma, while atopic dermatitis and allergic rhinitis share 88.7% (780/879) and 77.7% (923/1188) of genes with asthma. [Extracted from the article]

Multi-omics analyses implicate EARS2 in the pathogenesis of atopic dermatitis In conclusion, we used various omics profiles to construct a prediction model of AD and found several potentially crucial factors for the prediction, including the host expression of I EARS2 i . Keywords: atopic dermatitis; EARS2; multi-omics analysis; prediction model EN atopic dermatitis EARS2 multi-omics analysis prediction model 2602 2604 3 07/19/21 20210801 NES 210801 In recent years, omics data for studies on atopic dermatitis (AD) have become more available. [Extracted from the article]

Keywords: Emollient; atopic eczema; infancy EN Emollient atopic eczema infancy 2641 2643 3 07/19/21 20210801 NES 210801 Abbreviations FA food allergy FLG filaggrin gene AD atopic dermatitis TEWL transepidermal water loss BEEP Barrier Enhancement for Eczema Prevention PreventADALL Preventing Atopic Dermatitis and Allergies Atopic dermatitis/Eczema (AD) is the most common chronic inflammatory skin disease affecting up to 30% of children. It is unknown whether emollient usage may promote barrier integrity and affect the interplay between barrier impairment, skin inflammation, and ultimately prevent atopic dermatitis development. Thus, skin barrier dysfunction due to environmental factors and genetic predisposition paired with skin inflammation is linked to AD and consequently food sensitization, food allergy (FA), and progression of the allergic disease complex (Figure 1).1 The importance of barrier integrity for AD is supported by filaggrin (FLG). [Extracted from the article]

To the Editor, Atopic dermatitis (AD) is a prevalent inflammatory skin disease. The I FLG- i stratified analyses showed a trend toward cat exposure being a risk factor in children with I FLG i mutations and a protective factor in children without I FLG i mutations (Figure and Table S3). GLO:1X5/01jun20:all14162-fig-0001.jpg PHOTO (COLOR): Interaction between cat exposure and common FLG mutations in relation to (A) early-onset atopic dermatitis, (B) current atopic dermatitis, and (C) atopic dermatitis in the first 7 y of life gl We found no interaction between cat exposure in infancy and mutations in I FLG i on "early-onset AD" or "AD ever.". [Extracted from the article]

Allergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100 years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable "alternative" option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30 years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not "class‐related," as derived from meta‐analyses, but restricted to each specific product. The 30‐year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular‐based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities. [ABSTRACT FROM AUTHOR]

Adult patients, with moderate or severe AD, were randomized 1:1 to receive mepolizumab or placebo every 4 weeks on day 1, week 4, week 8, and week 12 of the 16-week treatment period. For the IGA endpoint, only 2 of 18 (11%) patients receiving mepolizumab and none of the 16 patients receiving placebo achieved treatment success at Week 16. This study did not show clinical improvement in patients with moderate/severe AD while receiving mepolizumab despite the observed blood eosinophils reduction and mepolizumab concentrations being consistent with that observed in patients with severe asthma. [Extracted from the article]

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes. [ABSTRACT FROM AUTHOR]

Allergies are typically endemic, complex and heterogeneous diseases with a high impact at quality of life. Mechanistically, type 2 immune responses involving eosinophil and basophil granulocytes, mast cells and humoral factors such as IgE are key drivers of allergic diseases. Fighting allergic diseases knows three strategies: prevention, symptomatic and causative therapy. While remarkable progress was made in understanding molecular events in allergies as a prerequisite for effective prevention and desensitization, this review article focuses on the most efficient symptomatic treatments—that is using more and more specific antibodies neutralizing particular immune pathways. We highlight and classify recent and upcoming developments in the three prototype chronic allergic diseases allergic asthma, chronic spontaneous urticaria and atopic eczema. In all three examples, biologics such as dupilumab or omalizumab become reliable and efficient therapeutic options. Finally, we give an outlook how a diagnostic and therapeutic workflow might look like in the near future for these three major burdens of society. [ABSTRACT FROM AUTHOR]

LAT1-specific inhibitor is effective against T cell-mediated allergic skin inflammation LAT1 inhibition alleviates T cell-dependent dermatitis by suppressing glycolysis/OXPHOS-cyclin/CDK axis in Th2 cells. LAT1 substrate depletion also impaired OXPHOS and glycolysis (Figure S3), implying that the JPH203-mediated down-regulation of OXPHOS and glycolysis is caused by amino acid starvation. The LAT1-glycolysis/OXPHOS-cyclin/CDK axis could provide an advantage to T cells for the adaptive tuning of cytokine production and cell proliferation in response to nutrient shortages (either glucose or amino acids). [Extracted from the article]

Background: Skin desquamation is facilitated by serine proteases KLK5 and KLK7, which are tightly regulated by lympho‐epithelial Kazal‐type related inhibitor (LEKTI). LEKTI itself is controlled through degraded by mesotrypsin. Here, we sought to determine whether LEKTI exonic mutations associated with atopic dermatitis (AD) affect the protease inhibitory activity of LEKTI or its susceptibility to mesotrypsin degradation. Methods: The inhibitory activities of the LEKTI domain 4 (D4) and D6 WT and AD‐associated mutants on the enzyme activities of KLK5 and KLK7 were compared using fluorogenic substrates. A keratinocyte cell culture system using HaCat cells was established to assess the role of D6 WT and D386N on triggering inflammation via the induction of thymic stromal lymphopoietin (TSLP). A degradation assay was used to assess the susceptibility of D4 and D6 mutants to mesotrypsin degradation. Results: Enzymatic assays revealed that the D6 D386N mutation affected the inhibitory activity of LEKTI on KLK5 but not KLK7. Other exonic mutations on D6 (N368S, V395M, and E420K) and D4 (R267Q) did not alter LEKTI inhibition. The D386N mutation disrupted the role of D6 in suppressing TSLP induction by KLK5 in HaCat cells. Although WT D4 is more susceptible to mesotrypsin degradation than WT D6, the D4 R267Q mutant was more resistant to mesotrypsin degradation, whereas the D6 E420K mutant showed enhanced mesotrypsin‐mediated degradation. Conclusion: Exonic mutations in D6, which previously have been associated with AD, may cause a disruption of inhibitory activity on KLK5 or enhance the degradation by mesotrypsin. [ABSTRACT FROM AUTHOR]

Background: Probiotic supplementation to mothers and/or their term‐born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. Methods: This sub‐study was an a priori secondary outcome of the ProPrems multi‐center, double‐blind, placebo‐controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. Results: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI −8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. Conclusion: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed. [ABSTRACT FROM AUTHOR]

Introduction: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. Objective: To study the effect of 16‐week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate‐severe AD in daily practice. Methods: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen‐week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI‐50 (Eczema Area and Severity Index) or EASI‐75, as well as patient‐reported outcomes measures (Patient‐Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty‐one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks). Results: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult‐to‐treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI‐50 and EASI‐75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity‐related serum biomarkers (TARC, PARC, periostin, and IL‐22), eotaxin‐1, and eotaxin‐3 significantly decreased. Conclusion: Treatment with dupilumab significantly improved disease severity and decreased severity‐related serum biomarkers in patients with very difficult‐to‐treat AD in a daily practice setting. [ABSTRACT FROM AUTHOR]

Background: New insights into immune cells could contribute to treatment and monitoring of atopic disease. Because nongenetic factors shape the human immune system, we here studied these immune cells in a large cohort with atopic children with adjustment for prenatal and postnatal confounders. Methods: Information on atopic dermatitis, inhalant‐ and food‐allergic sensitization, asthma lung function scores was obtained from 855 10‐year‐old children within the Generation R cohort. 11‐color flow cytometry was performed to determine CD27+ and CD27−IgG+, IgE+ and IgA+ memory B cells, Th1, Th2, Th17, and Treg‐memory cells from venous blood. Associations between any atopic disease, the individual atopic diseases, and immune cell numbers were determined. Results: Children with any atopic disease had higher Th2, Treg, Treg‐memory, and CD27+IgA+ memory B‐cell numbers compared to children without atopic disease. When studying the individual diseases compared to children without the individual diseases, children with atopic dermatitis, inhalant‐, and food‐allergic sensitization had higher memory Treg cell numbers 12.3% (95% CI 4.2; 21.0), (11.1% (95% CI 3.0; 19.8), (23.7% (95% CI 7.9; 41.8), respectively. Children with food‐allergic sensitization had higher total B and CD27+IgA+ memory B‐cell numbers (15.2% [95% CI 3.2; 28.7], 22.5% [95% CI 3.9; 44.3], respectively). No associations were observed between asthma and B‐ or T‐cell numbers. Conclusion: Children with any atopic disease and children with inhalant‐ and food‐allergic sensitization or atopic dermatitis had higher circulating memory Treg cells, but not higher IgE+B‐cell numbers. The associations of higher Treg and CD27+IgA+ B‐cell numbers in children with food‐allergic sensitization are suggestive of TGF‐β‐mediated compensation for chronic inflammation. [ABSTRACT FROM AUTHOR]

Eczema herpeticum (EH) is a severe and widespread viral skin infection caused by herpes simplex virus 1 (HSV-1), which particularly affects patients with atopic dermatitis (AD) who have a more severe course of the disease, higher allergen sensitization, and greater Th2 polarization.[[1]] The condition has been named ADEH (AD complicated by EH). Our study is the first to show specific IgE against HSV-1 in ADEH patients sera and it provides preliminary evidence of an increased type I and type IV hypersensitivity response to HSV-1 in these patients. A major allergen has been defined as one to which more than 50% of the sera of patients containing specific IgE to a specific allergenic source react. SP S13 sp Here, we showed that especially the viral proteins gD and VP22 were widely recognized by IgE from the ADEH patients sera. [Extracted from the article]

Background: The hygiene hypothesis proposes that reduced exposure to infectious agents in early life would explain the increase of allergic and autoimmune diseases observed over the past decades in high‐income countries. Methods: We conducted a matched case‐control study on incident atopic dermatitis (AD). Cases were 426 outpatient children with a first diagnosis of incident AD. Controls were 426 children attending a pediatric/dermatological visit for nonatopic disorders matched to cases (1:1). Particular attention was paid to the time elapsed between the markers of microbial exposure and disease onset, and we considered for controls the same time window of exposures from birth as his/her matched case. Odds ratios (ORs) were computed using multivariable conditional logistic regression models, according to center, sex, age, and period of enrollment, and including as potential confounders a family history of any allergy in parents, type of delivery, having siblings, keeping pets, age at weaning, and having had ≥4 infections. Results: The OR of AD first occurrence was 0.35 (P‐value =.039) for children who had experienced ≥4 infections compared with those with no infections. A decreasing trend in risk was observed with increasing number of siblings (P‐value =.023), the protective effect reaching about 40% for children with 2 or more siblings (OR = 0.62; P‐value =.048). Pet keeping, in particular daily contact with dogs, was inversely associated with AD risk (OR = 0.40; P‐value =.004). Conclusions: These results support the hygiene hypothesis in its broad sense. Early‐life environmental exposures, including pathogens and commensals, act as "microbes contact carriers" influencing immune system balance early in life. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)‐driven disease. Interleukin (IL)‐4 and IL‐13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor‐associated signal transduction machinery such as Janus kinases. Recently, IL‐13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL‐4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL‐13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL‐13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex inflammatory disorder with multiple interactions between genetic, immune and external factors. The sum of external factors that an individual is exposed to throughout their lifetime is termed the exposome. The exposome spans multiple domains from population to molecular levels and, in combination with genetic factors, holds the key to understanding the phenotypic diversity seen in AD patients. Exposomal domains are categorized into nonspecific (human and natural factors affecting populations), specific (eg humidity, ultraviolet radiation, diet, pollution, allergens, water hardness) and internal (cutaneous and gut microbiota and host cell interaction) exposures. The skin, as the organ that most directly interacts with and adapts to the external environment, is a prime target for exploration of exposomal influences on disease. Given the well‐recognized physical environmental influences on AD, this condition could be much better understood through insightful exposomal research. In this narrative review, we examine each domain in turn, highlighting current understanding of the mechanisms by which exposomal influences modulate AD pathogenesis at distinct points in time. We highlight current approaches to exposome modification in AD and other allergic disease and propose future directions for exposome characterization and modification using novel research techniques. [ABSTRACT FROM AUTHOR]

Background: The aim was to study the association between allergic multimorbidity and adult‐onset asthma considering the number of allergic diseases and the age effect. Methods: We used population‐based data from Finnish national registers including 1205 adults over 30 years of age with recently diagnosed asthma (age range: 30‐93), matched for gender, age, and living region with one or two controls (n = 2050). Allergic rhinitis (AR), allergic conjunctivitis (AC), and allergic dermatitis (AD) were defined from self‐completed questionnaire. Conditional logistic regression adjusted on potential confounders (smoking, growing in countryside, childhood hospitalized infection/pneumonia, parental asthma/allergy, parental smoking, education level, professional training, number of siblings, and birth order) was applied to estimate the asthma risk associated with allergic multimorbidity. Results: A total of 1118 cases with asthma and 1772 matched controls were included [mean (SD, min‐max) 53 (11, 31‐71) years, 37% men)]. AR, AC, and AD were reported by 50.2%, 39.6%, and 33.8%, respectively, among subjects with asthma and 26.1%, 20.0%, and 23.5%, respectively, among controls. Compared to nonatopics, adult‐onset asthma increased with the number of allergic diseases; adjusted OR for asthma [95% CI] associated with 1, 2, and 3 allergic diseases was 1.95 [1.52‐2.49], 2.87 [2.19‐3.77], and 4.26 [3.07‐5.90], respectively. The association between adult‐onset asthma and ≥ 1 allergic multimorbidity decreased with increasing age (3.52 [2.51‐4.94], 2.44 [1.74‐3.42], and 1.68 [1.04‐2.71]) in subjects < 50 years, 50‐62 years, and > 62 years, respectively (p for age*≥1 allergic multimorbidity interaction, 0.002). Conclusions: Adult‐onset asthma was positively associated with the number of allergic diseases, and this association decreases with age. [ABSTRACT FROM AUTHOR]

Background: Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3‐ to 15‐month‐olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA. Methods: The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ≥5 kUA/L, otherwise ≥14 kUA/L, peanut IgE)] among 511 participants (median follow‐up, 7.3 years). Associations were explored with univariate logistic regression; factors with P < 0.15 were analyzed by stepwise multiple logistic regression, using data stratified by PNA status and randomly assigned to development and validation datasets. Results: 205/511 (40.1%) had PNA. Univariate factors associated with PNA (P < 0.01) included increased AD severity, larger egg and peanut SPT, greater egg, milk, peanut, Ara h1‐h3 IgE, higher peanut IgG and IgG4, and increased pregnancy peanut consumption. P‐values were between 0.01 and 0.05 for younger age, non‐white race, lack of breastfeeding, and increased lactation peanut consumption. Using a development dataset, the multivariate model identified younger age at enrollment, greater peanut and Ara h2 IgE, and lack of breastfeeding as prognosticators. The final model predicted 79% in the development and 75% in the validation dataset (AUC = 0.83 for both). Models using stricter or less strict PNA criteria both found Ara h2 as predictive. Conclusions: Key factors associated with PNA in this high‐risk population included lack of breastfeeding, age, and greater Ara h2 and peanut‐specific IgE, which can be used to prognosticate outcomes. [ABSTRACT FROM AUTHOR]

Background: The prevention of food allergy is a key priority for reducing the burden of allergic disease. Environmental exposures modulate the risk of developing food allergy and some of this may be mediated by the infants' developing microbiome. However, the role of potentially protective environmental exposures, such as pet ownership, is largely uninvestigated with respect to food allergy. Methods: We performed a secondary cohort analysis in the Enquiring About Tolerance (EAT) study, which enrolled 1303 three‐month infants onto a randomized trial to prevent food allergy. A survey elicited domestic animal ownership and participants were examined for atopic dermatitis (AD) at enrolment. Sensitization to foods and aeroallergens were elicited by skin and serum testing at 3, 12 and 36 months. Food allergy status was determined by double‐blind placebo‐controlled food challenges between 1 and 3 years. Results: Food allergy was diagnosed amongst 6.1% (68/1124) of participants with complete data. No significant relationships were demonstrated between food allergy and caesarean delivery, infections or antibiotic exposure in early life. After adjusting for familial atopic disease, maternal dog/cat sensitization and participant AD, living with dogs was associated with a 90% reduction in the odds of infants developing food allergy (adjusted odds ratio (aOR) 0.10 (confidence interval (CI) 0.01‐0.71), P = 0.02). None of the 49 infants living with at least two dogs developed food allergy, suggesting a dose‐response relationship (each dog owned aOR 0.12 (CI 0.02‐0.81), P = 0.03). No relationship was demonstrated between owning dogs or cats and the development of AD. Conclusion: Dog ownership in infancy may prevent food allergy. [ABSTRACT FROM AUTHOR]

Background: miR‐10a‐5p has been shown to regulate cancer cell proliferation and invasiveness and endothelial cell inflammatory responses. The function of miR‐10a‐5p in the skin has not been previously studied. The aim of the current study was to examine miR‐10a‐5p expression, regulation, and function in keratinocytes (KCs) in association with atopic dermatitis (AD). Methods: The expression of miR‐10a‐5p and its target genes was analyzed using RT‐qPCR, mRNA array analysis, in situ hybridization, and immunofluorescence. The transfection of miRNA mimics, cell cycle distribution analysis, and luciferase assays was used to study miR‐10a‐5p functions in human primary KCs. Results: miR‐10a‐5p was found to be upregulated in lesional skin from patients with AD and in proliferating KCs. Array and pathway analysis of IL‐1β‐stimulated KCs revealed that miR‐10a‐5p inhibited many genes that affect cell cycle progression and only a few inflammation‐related genes. Accordingly, fewer cells in S‐phase and reduced proliferation were detected as characteristics of miR‐10a‐5p‐transfected KCs. The influence of miR‐10a‐5p on cell proliferation was also evident in KCs induced by AD‐related cytokines, including IL‐4, IL‐17, and IL‐1β, as measured by the capacity to strongly suppress the expression of the proliferation marker Ki‐67. Among AD‐related putative direct target genes, we verified hyaluronan synthase 3, a damage‐associated positive regulator of KC migration and proliferation, as a direct target of miR‐10a‐5p. Conclusions: miR‐10a‐5p inhibits KC proliferation and directly targets hyaluronan synthase 3 and thereby may modulate AD‐associated processes in the skin. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is being recognized as a major cofactor in atopic diseases such as atopic dermatitis, chronic rhinosinusitis with nasal polyps, and asthma. The understanding of the relationship between S aureus virulence factors and the immune system is continuously improving. Although the precise mechanism of the host's immune response adaptation to the variable secretion profile of S aureus strains continues to be a matter of debate, an increasing number of studies have reported on central effects of S aureus secretome in allergy. In this review, we discuss how colonization of S aureus modulates the innate and adaptive immune response, thereby predisposing the organism to allergic sensitization and disrupting immune tolerance in the airways of patients with asthma and chronic rhinosinusitis with nasal polyps. Next, we provide a critical overview of novel concepts dealing with S aureus in the initiation and persistence of chronic rhinosinusitis with nasal polyps and asthma. The role of the S aureus serine protease‐like proteins in the initiation of a type 2 response and the contribution of the IL‐33/ST2 signaling axis in allergic responses induced by bacterial allergens are discussed. [ABSTRACT FROM AUTHOR]