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Objective: To evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication. Methods: PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures. Results: A total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84–12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89–22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63–9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93–14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60–11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26–20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09–1.58), P = 0.004] [OR = 1.85, 95% CI (1.54–2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41–1.29), P = 0.28] [OR = 0.69, 95% CI (0.39–1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39–1.11), P = 0.12] [OR = 0.85, 95% CI (0.52–1.38), P = 0.50]} compared to placebo. Conclusion: This meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose. [ABSTRACT FROM AUTHOR]

Background: The association between atopic dermatitis and childhood overweight and obesity has been studied extensively, but the results are inconclusive; most studies have focused on body mass index as a measure of obesity, with few investigating the relationship with underweight. Therefore, this study aimed to investigate the association between body mass index levels and atopic dermatitis in Korean adolescents. Methods: 3-year (2019–2021) of Korea Youth Risk Behavior Web-based Survey were used. Body mass index was used to measure obesity and a recent diagnosis within the past year was used as the criterion for atopic dermatitis. Multiple logistic regression analyses were performed to explore the associations. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 144,183 adolescents aged 12–18 years were included in this study (74,704 males and 69,479 females). Over the past year, 5.4% of males and 7.3% of females were diagnosed with atopic dermatitis in the study population. Adolescents with normal weight (males [OR: 1.19, CI: 1.02–1.38]; females [OR: 1.26, CI: 1.10–1.43]) and overweight (males [OR: 1.37, CI: 1.16–1.61]; females [OR: 1.37, CI: 1.19–1.58]) were more likely to develop atopic dermatitis than underweight. Conclusion: Increased degree of obesity may contribute to the development of atopic dermatitis. The normal-weight and obese adolescents had higher likelihood of developing atopic dermatitis compared with the underweight adolescents. [ABSTRACT FROM AUTHOR]

Air pollution causes and exacerbates allergic diseases including asthma, allergic rhinitis, and atopic dermatitis. Precise prediction of the number of patients afflicted with these diseases and analysis of the environmental conditions that contribute to disease outbreaks play crucial roles in the effective management of hospital services. Therefore, this study aims to predict the daily number of patients with these allergic diseases and determine the impact of particulate matter (PM10) on each disease. To analyze the spatiotemporal correlations between allergic diseases (asthma, atopic dermatitis, and allergic rhinitis) and PM10 concentrations, we propose a multi-variable spatiotemporal graph convolutional network (MST-GCN)-based disease prediction model. Data on the number of patients were collected from the National Health Insurance Service from January 2013 to December 2017, and the PM10 data were collected from Airkorea during the same period. As a result, the proposed disease prediction model showed higher performance (R2 0.87) than the other deep-learning baseline methods. The synergic effect of spatial and temporal analyses improved the prediction performance of the number of patients. The prediction accuracies for allergic rhinitis, asthma, and atopic dermatitis achieved R2 scores of 0.96, 0.92, and 0.86, respectively. In the ablation study of environmental factors, PM10 improved the prediction accuracy by 10.13%, based on the R2 score. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a multi-pathogenic disease characterized by chronic skin inflammation and barrier dysfunction. Therefore, improving the skin's ability to form an epidermal barrier and suppressing the production of cytokines that induce type 2 inflammatory responses are important for controlling atopic dermatitis symptoms. (-)-Blebbistatin, a non-muscle myosin II inhibitor, has been suggested to improve pulmonary endothelial barrier function and control inflammation by suppressing immune cell migration; however, its efficacy in atopic dermatitis is unknown. In this study, we investigated whether (S)-(-)-blebbistatin O-benzoate, a derivative of (-)-blebbistatin, improves dermatitis symptoms in a mite antigen-induced atopic dermatitis model using NC/Nga mice. The efficacy of the compound was confirmed using dermatitis scores, ear thickness measurements, serum IgE levels, histological analysis of lesions, and filaggrin expression analysis, which is important for barrier function. (S)-(-)-Blebbistatin O-benzoate treatment significantly reduced the dermatitis score and serum IgE levels compared to those in the vehicle group (p < 0.05). Furthermore, the histological analysis revealed enhanced filaggrin production and a decreased number of mast cells (p < 0.05), indicating that (S)-(-)-blebbistatin O-benzoate improved atopic dermatitis symptoms in a pathological model. In vitro analysis using cultured keratinocytes revealed increased expression of filaggrin, loricrin, involucrin, and ceramide production pathway-related genes, suggesting that (S)-(-)-blebbistatin O-benzoate promotes epidermal barrier formation. Furthermore, the effect of (S)-(-)-blebbistatin O-benzoate on type 2 alarmin cytokines, which are secreted from epidermal cells upon scratching or allergen stimulation and are involved in the pathogenesis of atopic dermatitis, was evaluated using antigens derived from mite feces. The results showed that (S)-(-)-blebbistatin O-benzoate inhibited the upregulation of these cytokines. Based on the above, (S)-(-)-blebbistatin O-benzoate has the potential to be developed as an atopic dermatitis treatment option that controls dermatitis symptoms by suppressing inflammation and improving barrier function by acting on multiple aspects of the pathogenesis of atopic dermatitis. [ABSTRACT FROM AUTHOR]

The human skin virome, unlike commensal bacteria, is an under investigated component of the human skin microbiome. We developed a sensitive, quantitative assay to detect cutaneous human resident papillomaviruses (HPV) and polyomaviruses (HPyV) and we first used it to describe these viral populations at the skin surface of two patients with atopic dermatitis (AD) and psoriasis (PSO). We performed skin swabs on lesional and non-lesional skin in one AD and one PSO patient at M0, M1 and M3. After extraction, DNA was amplified using an original multiplex PCR technique before high throughput sequencing (HTS) of the amplicons (named AmpliSeq-HTS). Quantitative results were ultimately compared with monoplex quantitative PCRs (qPCRs) for previously detected viruses and were significantly correlated (R2 = 0.95, ρ = 0.75). Fifteen and 13 HPV types (mainly gamma and beta-HPVs) or HPyV species (mainly Merkel Cell Polyomavirus (MCPyV)) were detected on the skin of the AD and PSO patients, respectively. In both patients, the composition of the viral flora was variable across body sites but remained stable over time in non-lesional skin samples, mostly colonized with gamma-papillomaviruses. In lesional skin samples, beta-papillomaviruses and MCPyV were the major components of a viral flora more prone to vary over time especially with treatment and subsequent clinical improvement. We believe this method might be further used in extensive studies to further enhance the concept of an individual cutaneous viral fingerprint and the putative role of its alterations through various skin diseases and their treatments. [ABSTRACT FROM AUTHOR]

During recent decades, allergy related diseases have emerged as a growing area of concern in developing regions of the world, including Africa. Worldwide prevalence of allergic diseases has grown to an estimated 262 million for asthma, 400 million for allergic rhinitis (or hay fever), 171 million with atopic dermatitis (or eczema), and over 200 million for food allergy. In Africa, considerable variability exists in the data surrounding prevalence at the continent-wide, regional, and study site levels. Furthermore, research conducted in many rural areas and underdeveloped countries in Africa remains limited, and presently, little has been done to characterize and map the extremely heterogeneous body of literature which confounds research efforts. This scoping review will seek to identify studies examining the prevalence, management strategies, outcomes, and associated risk factors for allergy related diseases in Africa. The Joanna Briggs Institute's scoping review methods will be followed, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR) was used for writing the protocol. Four databases (Embase, Global Health, PubMed, African Journals Online) will be searched for literature published from 2003 to 2023 in any language. Title and abstract screening and full-text screening will be completed by two independent reviewers using Covidence; conflicts resolved by a third reviewer. Data will be extracted using Covidence by two reviewers independently. To report the results, we will follow the PRISMA-ScR checklist and report descriptive statistics and a narrative summary. [ABSTRACT FROM AUTHOR]

In atopic dermatitis (AD), nerves are abnormally stretched near the surface of the skin, making it sensitive to itching. Expression of neurotrophic factor Artemin (ARTN) involved in such nerve stretching is induced by the xenobiotic response (XRE) to air pollutants and UV radiation products. Therefore, AD can be monitored by the XRE response. Previously, we established a human keratinocyte cell line stably expressing a NanoLuc reporter gene downstream of XRE. We found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan metabolite and known inducer of the XRE, increased reporter and Artemin mRNA expression, indicating that FICZ-treated cells could be a model for AD. Lavender essential oil has been used in folk medicine to treat AD, but the scientific basis for its use is unclear. In the present study, we investigated the efficacy of lavender essential oil and its major components, linalyl acetate and linalool, to suppress AD and sensitize skin using the established AD model cell line, and keratinocyte and dendritic cell activation assays. Our results indicated that lavender essential oil from L. angustifolia and linalyl acetate exerted a strong AD inhibitory effect and almost no skin sensitization. Our model is useful in that it can circumvent the practice of using animal studies to evaluate AD medicines. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflammatory skin condition that relies largely on subjective evaluation of clinical signs and symptoms for diagnosis and severity assessment. Using multivariate data, we attempted to construct prediction models that can diagnose the disease and assess its severity. We combined data from 28 mild-moderate AD patients and 20 healthy controls (HC) to create random forest models for classification (AD vs. HC) and regression analysis to predict symptom severities. The classification model outperformed the random permutation model significantly (area under the curve: 0.85 ± 0.10 vs. 0.50 ± 0.15; balanced accuracy: 0.81 ± 0.15 vs. 0.50 ± 0.15). Correlation analysis revealed a significant positive correlation between measured and predicted total SCORing Atopic Dermatitis score (SCORAD; r = 0.43), objective SCORAD (r = 0.53), eczema area and severity index scores (r = 0.58, each p < 0.001), but not between measured and predicted itch ratings (r = 0.21, p = 0.18). We developed and tested multivariate prediction models and identified important features using a variety of serum biomarkers, implying that discovering the deep-branching relationships between clinical measurements and serum measurements in mild-moderate AD patients may be possible using a multivariate machine learning method. We also suggest future methods for utilizing machine learning algorithms to enhance drug target selection, diagnosis, prognosis, and customized treatment in AD. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive dysfunction, but the results of individual studies have been inconsistent. This systematic review and meta-analysis aimed to evaluate the association between AD and cognitive dysfunction in middle-aged and older adults. Methods: To find relevant research, a comprehensive search of electronic databases from the beginning to March 2023 was carried out. Data were taken from studies that were eligible, and a meta-analysis was done to determine the pooled hazard ratio (HR) and 95% confidence interval (CI). Results: We searched three databases and found a total of 15 studied arms included in 5 cohort studies with over 8.5 million participants were included in the analysis. The results showed that individuals with AD had a higher risk of developing dementia of all-cause dementia (pooled hazard ratio (HR) = 1.16; 95% CI, 1.10–1.23,P<0.001) and the Alzheimer type (pooled HR = 1.28; 95% CI, 1.01–1.63,P<0.001) but not vascular dementia (pooled HR = 1.42; 95% CI, 0.99–2.04,P<0.001). Subgroup analyses showed that the association between atopic dermatitis and all-cause dementia was significant in Europe (P = 0.004) but not in Asia (P = 0.173) and was significant in prospective cohort studies (P<0.001) but not in non-prospective cohort studies (P = 0.068). Sensitivity analysis and publication bias detection confirmed the reliability of the overall findings. Conclusions: In conclusion, this study demonstrated that AD was associated with increased risk of cognitive dysfunction, particularly dementia of the Alzheimer type and all-cause dementia, in middle-aged and older participants. Further research is needed to understand the mechanisms behind this association and its potential implications for clinical practice. Systematic review registration: PROSPERO, identifier (CRD42023411627). [ABSTRACT FROM AUTHOR]

With mutations constantly accumulating in bacterial genomes, it is unclear whether the previously identified bacterial strains are really present in an extant sample. To address this question, we did a case study on the known strains of the bacterial species S. aureus and S. epidermis in 68 atopic dermatitis shotgun metagenomic samples. We evaluated the likelihood of the presence of all sixteen known strains predicted in the original study and by two popular tools in this study. We found that even with the same tool, only two known strains were predicted by the original study and this study. Moreover, none of the sixteen known strains was likely present in these 68 samples. Our study thus indicates the limitation of the known-strain-based studies, especially those on rapidly evolving bacterial species. It implies the unlikely presence of the previously identified known strains in a current environmental sample. It also called for de novo bacterial strain identification directly from shotgun metagenomic reads. [ABSTRACT FROM AUTHOR]

The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now estimated that up to 20% of the global population is afflicted by an allergic disease, with increasing incidence rates in both high- and low-income countries. The World Allergy Organization estimates that the total economic burden of asthma and allergic rhinitis alone is approximately $21 billion per year. While allergic stimuli are a complex and heterogenous class of inputs including parasites, pollens, food antigens, drugs, and metals, it has become clear that fungi are major drivers of allergic disease, with estimates that fungal sensitization occurs in 20–30% of atopic individuals and up to 80% of asthma patients. Fungi are eukaryotic microorganisms that can be found throughout the world in high abundance in both indoor and outdoor environments. Understanding how and why fungi act as triggers of allergic type 2 inflammation will be crucial for combating this important health problem. In recent years, there have been significant advances in our understanding of fungi-induced type 2 immunity, however there is still much we don't understand, including why fungi have a tendency to induce allergic reactions in the first place. Here, we will discuss how fungi trigger type 2 immune responses and posit why this response has been evolutionarily selected for induction during fungal encounter. [ABSTRACT FROM AUTHOR]

The progression of allergic diseases from atopic dermatitis in childhood to other allergic conditions such as asthma in later life is often referred to as the atopic march. In order to study the relationship between cutaneous sensitization by aeroallergen and atopic march, we established a mouse model to test the hypothesis using American cockroaches and house dust mites as the model allergens. Mice were sensitized via skin with native cockroach extract (CraA) or recombinant Per a 2 and Der p 2 proteins without adjuvant. Each mouse was subjected to a total of three 1-week patching sensitizations with a 2-week interval in between each application. The resulting immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of skin lesions and nasal mucosa were evaluated. In mice, application of CraA, rPer a 2, and rDer p 2 aeroallergens through skin patching induced significantly high levels of both total IgE and specific IgEs. The epicutaneous sensitization after a subsequent allergen challenge showed a significant increase in scratch bouts, AHR, epidermal thickness, and eosinophil counts in the skin compared with the control mice. In addition, stimulation of murine splenocytes with allergens increased higher levels of Th2 cytokines, anti-inflammatory cytokines, and chemokines excretion. Our study provides evidence supporting that epicutaneous sensitization to aeroallergens also led to nasal and airway symptoms comparable to atopic march as described in humans. We hope this new allergy model will be useful in the development of new preventive and therapeutic strategies aimed at stopping the atopic march. [ABSTRACT FROM AUTHOR]

This cross-sectional, retrospective, observational study aimed to analyze the distribution and healthcare usage patterns of patients with atopic dermatitis using the 2010–2018 Health Insurance Review and Assessment Service data. Patients diagnosed with atopic dermatitis in Korea between January 2010 and December 2018 and registered in the Health Insurance Review and Assessment national database were identified, and 270,008 patients who used healthcare services at least once during this period were evaluated to ascertain the healthcare usage patterns and treatment methods for atopic dermatitis. The number of patients with atopic dermatitis plateaued during the study period, while the number of claims and total expenses increased by a small margin. Atopic dermatitis prevalence was the highest among patients aged <5 years (31.4%), followed by those aged 5–14 years (23.53%) and 15–24 years (15.33%). However, the prevalence in these age groups showed a decreasing trend over time. The most used Western medicine treatments were injections and oral medications involving topical corticosteroids, antihistamine agents, and oral steroids, while it was acupuncture therapy in Korean medicine. The frequency of the most frequently prescribed medication, topical corticosteroid, showed a decreasing trend over time. The findings in this study will inform healthcare policy makers and clinicians across different countries on the usage trends of Western medicine and Korean medicine treatment. [ABSTRACT FROM AUTHOR]

We recently used EPA databases to identify that isocyanates, most notably toluene diisocyanate (TDI), were the pollutant class with the strongest spatiotemporal and epidemiologic association with atopic dermatitis (AD). Our findings demonstrated that isocyanates like TDI disrupted lipid homeostasis and modeled benefit in commensal bacteria like Roseomonas mucosa through disrupting nitrogen fixation. However, TDI has also been established to activate transient receptor potential ankyrin 1 (TRPA1) in mice and thus could directly contribute to AD through induction of itch, rash, and psychological stress. Using cell culture and mouse models, we now demonstrate that TDI induced skin inflammation in mice as well as calcium influx in human neurons; each of these findings were dependent on TRPA1. Furthermore, TRPA1 blockade synergized with R. mucosa treatment in mice to improve TDI-independent models of AD. Finally, we show that the cellular effects of TRPA1 are related to shifting the balance of the tyrosine metabolites epinephrine and dopamine. This work provides added insight into the potential role, and therapeutic potential, or TRPA1 in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Background: As atopic dermatitis (AD) has been found to be related to various comorbidities as well as substantial patient burden, questions of a possible relationship between AD and nonallergic diseases beyond allergic diseases have also been raised. Objective: The aim of this nationwide matched cohort study was to evaluate whether AD would increase the development of gastroesophageal reflux disease (GERD). Methods: Patients diagnosed with AD were identified from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database in South Korea from 2002 to 2015. Finally, 9,164 adults with AD (≥20 years old) and age, sex, household income, region of residence, disability, and baseline year-matched 9,164 controls were included in the analysis. Hazard ratio (HR) with 95% confidence interval (CI) for the development of GERD was estimated using a Cox proportional hazard regression model. Results: Overall, 12.3% of the patients in the AD group developed GERD, whereas 10.4% of the individuals in the control group developed GERD. The results of the adjusted model revealed that patients with AD had a significantly increased risk of developing GERD (adjusted HR, 1.15; 95% CI, 1.06–1.26) compared with the matched controls. Increased risk of developing GERD was consistent in subgroup analyses by sex or age groups under 60 years old as well as all the sensitivity analyses performed. Conclusions: This study suggested that appropriate management should be considered in adults with AD to prevent GERD, because AD was found to be associated with an increased risk of subsequent GERD. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic pruritic inflammatory skin disease commonly occurring in children. The objective of this study is to evaluate the treatment of pediatric atopic dermatitis with biologics, as they have displayed immense promising results in several recent clinical trials on atopic dermatitis (AD). Methods: We will conduct an extensive search for RCTs in several databases, including Embase, Cochrane Library, Web of Science, and PubMed, from the inception of the study till 15th May 2022. The primary outcomes will be the proportion of patients with EASI 75/90/100 after 12–16 weeks of treatment. The secondary outcomes will include the Numerical Rating Scale (NRS), Investigator Global Assessment (IGA)0–1, body surface area (BSA), Dermatology Life Quality Index (DLQI) scores, and incidence of adverse reactions. All studies will be screened by two independent researchers. They will assess the risk of bias in the included studies according to the RCTs bias risk evaluation tool in Cochrane System Review Manual 5.1.0. Meta-analysis will be performed using RevMan V.5.3.0 software. Results: The research results will provide a reference for the clinical application of biological agents in pediatric atopic dermatitis. Conclusion: We aim to evaluate the efficacy and safety of biologics in pediatric atopic dermatitis cases and provide evidence-based data for easy clinical application. PROSPERO registration number: CRD42022319052 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage). [ABSTRACT FROM AUTHOR]

Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1–3.2), 2.0 (1.5–2.5), 1.6 (1.2–2.1), and 0.7 (0.5–1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) primarily affects the pediatric population, which is highly colonized by S. aureus. However, little is known about the genetic features of this microorganism and other staphylococcal species that colonize AD patients. Objective: This study aimed to characterize Staphylococcus spp. isolated from the nares and skin (with and without lesion) of 30 AD and 12 non-AD Brazilian children. Methods: Skin and nasal swabs were cultured onto mannitol salt agar, and bacterial colonies were counted and identified by matrix assisted laser desorption ionization time of flight mass spectrometry and polymerase chain reaction (PCR). Antimicrobial susceptibility was evaluated by phenotypic and genotypic tests. In S. aureus isolates, Panton-Valentine leukocidin genes were detected by PCR, and their clonality was assessed by pulsed-field gel electrophoresis and multilocus sequence typing. Results: S. aureus was more prevalent in the nares (P = 0.005) and lesional skin (P = 0.0002) of children with AD, while S. hominis was more frequent in the skin of non-AD children (P < 0.0001). All children in the study, except one from each group, were colonized by methicillin-resistant coagulase-negative Staphylococcus and 24% by methicillin-resistant S. aureus. Despite the great clonal diversity of S. aureus (18 sequence types identified), most AD children (74.1%) were colonized by the same genotype in both niches. Conclusion: High colonization by polyclonal S. aureus isolates was found among children with AD, while S. hominis was more frequent among non-AD children. The high prevalence of methicillin-resistant staphylococcal isolates highlights the importance of continued surveillance, especially when considering empiric antibiotic therapy for the treatment of skin infections in these patients. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence shows allergic diseases, such as atopic dermatitis and asthma, are risk factors of heart failure. However, the causal relationship between allergic diseases and heart failure is not clear. Methods: We performed a two-sample Mendelian randomization analysis between allergic diseases and heart failure using summary statistics of genome-wide association studies from large GWAS consortia, with total sample size of 1.2 million. Independent instrumental variables for asthma and atopic dermatitis (P<1×10−5) were used as the exposure. We applied five models for the Mendelian randomization analysis. Finally, we performed the sensitivity analyses to assess the robustness of the results. Results: We have identified 55 independent single nucleotide polymorphisms (SNPs) for asthma 54 independent SNPs for atopic dermatitis as our instrumental variables. The inverse variance-weighted (IVW) analysis showed asthma was significantly associated with increased risk of heart failure (ORIVW = 1.04, 95% CI, 1.01–1.07, P = 0.03). The Mendelian randomization analysis using the other four models also showed consistent results with the IVW analysis. Similarly, atopic dermatitis was also significantly associated with an increased risk of heart failure (ORIVW = 1.03, 95% CI, 1.01–1.06, P = 0.01), consistent with the other four models. The sensitivity analysis showed no evidence of horizontal pleiotropy or results were driven by single SNPs. Conclusion: Our study identified asthma and atopic dermatitis as a causal risk factor for heart failure and suggest inflammatory pathogenesis as a key factor contributing to the underlying mechanism. These findings emphasize the importance of asthma and allergy control in the prevention and management of heart failure. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is a human antibody that blocks the signaling of both interleukin-4 and interleukin-13 receptors. It has been approved for the treatment of moderate-to-severe atopic dermatitis. However, several case reports have reported conflicting effects of dupilumab on alopecia. Objectives: This study aimed to examine dupilumab-related hair disorders using the large real-world database, VigiBase. Methods: All individual case safety reports associated with dupilumab in the Uppsala Monitoring Center VigiBase until December 29, 2019, were analyzed. Hair disorder-related terms were defined in High Level Terms with "alopecias," "pilar disorders NEC (not elsewhere classified)," and "hypertrichoses," using the Medical Dictionary for Regulatory Activities Hierarchy. Hair disorder reports associated with dupilumab and other biologics that inhibit the Th2 axis (omalizumab, mepolizumab, reslizumab, and benralizumab) were analyzed to determine their association with hair disorders. Disproportionality analysis was performed based on the proportional reporting ratio, reporting odds ratio, and information components. Results: Among the 20,548 total dupilumab adverse event (AE) reports, hair disorders were reported in 462 dupilumab cases (2.2%), most of which reported hair loss, and only eight cases reported an increase in hair growth. The paradoxical trend in hair loss and growth after dupilumab use was confirmed using a disproportionality analysis. Among the other investigated biologics on Th2 immunity, only omalizumab was associated with hair loss. Additionally, hair disorders after dupilumab treatment were more frequently reported in women than in men. The proportion of hair disorder cases was high in Europe, accounting for 20.8% of hair disorder reports, whereas only 9.7% of all dupilumab-related AEs were reported in Europe. In conclusion, our analysis using a large real-world database confirmed that dupilumab is associated with hair disorders. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells. To understand the differences in gene regulatory activity in peripheral blood T cells in AD, we measured chromatin accessibility (an assay based on transposase-accessible chromatin sequencing, ATAC-seq), nuclear factor kappa B subunit 1 (NFKB1) binding (chromatin immunoprecipitation with sequencing, ChIP-seq), and gene expression levels (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD, as well as in age-matched and non-allergic controls. Open chromatin regions in stimulated CD4+ T cells were highly enriched for AD genetic risk variants, with almost half of the AD risk loci overlapping AD-dependent ATAC-seq peaks. AD-specific open chromatin regions were strongly enriched for NF-κB DNA-binding motifs. ChIP-seq identified hundreds of NFKB1-occupied genomic loci that were AD- or control-specific. As expected, the AD-specific ChIP-seq peaks were strongly enriched for NF-κB DNA-binding motifs. Surprisingly, control-specific NFKB1 ChIP-seq peaks were not enriched for NFKB1 motifs, but instead contained motifs for other classes of human transcription factors, suggesting a mechanism involving altered indirect NFKB1 binding. Using DNA sequencing data, we identified 63 instances of altered genotype-dependent chromatin accessibility at 36 AD risk variant loci (30% of AD risk loci) that might lead to genotype-dependent gene expression. Based on these findings, we propose that CD4+ T cells respond to stimulation in an AD-specific manner, resulting in disease- and genotype-dependent chromatin accessibility alterations involving NFKB1 binding. Author summary: Gene expression is regulated in stimulated CD4+ T cells in a disease-dependent manner in patients with atopic dermatitis (AD). AD-specific regions of chromatin accessibility and binding of the NFKB1 transcription factor are enriched for AD genetic risk variants. Clinically, CD4+ T cells in the peripheral blood of patients with AD respond to stimulation in a disease- and genotype-dependent manner. [ABSTRACT FROM AUTHOR]

Objective: To determine the climate conditions that affect the incidence of atopic dermatitis from infancy to 3 years old. Study design: We analyzed 100,303 children born from 2011 to 2014 for follow-up until 3 years old using cohort data from the Japan Environment and Children's Study. The study included 15 Regional Centers, including 19 prefectures across Japan. We used meteorological data of the Japan Meteorological Agency. We calculated the hazard ratio (HR) of the standard deviation and low vs. high mean values of several climate conditions in children in their first 6 months of life to determine the incidence of atopic dermatitis. Results: The Kaplan–Meier curve showed that children born in the months of October to December had the highest incidence of atopic dermatitis. Among climate conditions, a one standard deviation increase in the temperature (HR = 0.87), minimum temperature (HR = 0.87), and vapor pressure (HR = 0.87) showed the lowest HRs for the incidence of atopic dermatitis. These results were confirmed by an analysis by strata of the birth season. A low vapor pressure (HR = 1.26, p<0.0001) and the combination of a low mean temperature or low mean minimum temperature and low vapor pressure (HR = 1.26, p<0.0001) were associated with the highest incidence of atopic dermatitis. These results were consistent when they were adjusted for a maternal and paternal history of allergy and the prefecture of birth. Conclusion: Among climate conditions, a low vapor pressure is the most strongly associated with a high incidence of atopic dermatitis. Measuring vapor pressure may be useful for preventing atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Skin colonization with coagulase-negative staphylococci (CoNS) is generally beneficial, but recent investigations suggest its association with flares and atopic dermatitis (AD) severity. However, this relationship remains unclear. Objective: To assess patterns of staphylococcal colonization and biofilm formation in toddlers with and without AD from rural and urban South African settings. Methods: We conducted a cross-sectional study of AD-affected and non-atopic AmaXhosa toddlers from rural Umtata and urban Cape Town, South Africa. CoNS isolates were recovered from lesional, nonlesional skin samples and the anterior nares of participants. Identification of the staphylococci was achieved by MALDI-TOF mass spectrometry. The microtiter plate assay assessed in-vitro biofilm formation. Results: CoNS and S. aureus commonly co-colonized nonlesional skin among cases (urban: 24% vs. 3%, p = 0.037 and rural 21% vs. 6%, p<0.001), and anterior nares in urban cases (24% vs. 0%, p = 0.002) than the control group. S. capitis colonization on nonlesional skin and anterior nares was positively associated with more severe disease in rural (48.3±10.8 vs. 39.7±11.5, P = 0.045) and urban cases (74.9±10.3 vs. 38.4±13, P = 0.004), respectively. Biofilm formation was similar between cases and controls, independent of rural-urban living. Conclusion: CoNS colonization is associated with AD and disease severity and may be implicated in AD exacerbations. Studies are needed to understand their underlying pathological contribution in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases. Methods: We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected. Results: Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30). Conclusions: Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to analyze the gender-specific association of the filaggrin (FLG) gene polymorphisms with atopic dermatitis (AD) in Caucasians from the central region of Russia. Methods: The study sample consisted of 906 female (including 474 patients with AD and 432 controls) and 406 male (such as 226 patients with AD and 180 controls) participants. Genotyping of ten polymorphisms of the FLG gene was done. The logistic regression was used to analyze the associations. A total of 125 SNPs (seven AD-associated SNPs and 118 proxy SNPs, r2≥0.8) FLG gene were used for the in silico functional annotation analysis in the females. Results: Significant associations were identified between seven SNPs of the FLG gene (rs12130219, rs61816761, rs558269137, rs12144049, rs3126085, rs471144, rs6661961) and AD in females: rs12144049 was associated independent individually (for allele C OR = 1.71, 95%Сl 1.19–2.46, рperm = 0.004 and OR = 1.76, 95%Сl 1.18–2.63, рperm = 0.006 according to the additive and dominant genetic models, respectively) and seven SNPs of the FLG gene within 14 haplotypes. Haplotype GGT [rs61816761-rs3126085-rs12144049] showed the strongest association (OR = 0.55, рperm = 0.001). No association between the analyzed SNPs and AD was determined in the male group. The subsequent bioinformatic analysis predicted the SNPs of the FLG gene that possessed epigenetic and non-synonymous effects, were involved in the control of gene expression and alternative splicing of genes that contribute to AD pathophysiology. Conclusion: Polymorphisms of the FLG gene are associated with AD in females but not in males in the Caucasian population of Central Russia. [ABSTRACT FROM AUTHOR]

Skin inflammation leads to altered cytokine/chemokine production and causes systemic inflammation. The systemic mechanism of atopic dermatitis (AD) is recognized to affect systemic metabolism. This study aimed to examine the relationship between early-onset persistent eczema and body weight, height, and body mass index (BMI), in addition to food allergy in a birth cohort among infants. This study design was a nationwide, multicenter, prospective birth cohort study—the Japan Environment and Children's Study (JECS). Generalized linear models were fitted for z scores of weight, height, BMI, and food allergy to evaluate the relationship between eczema and these outcomes for infants at age1, 2, and 3 years. Persistent eczema was negatively associated with height at the age of 2 years (estimated coefficient, −0.127; 95% confidence interval [CI], −0.16 to −0.095) and 3 years (−0.177; 95% CI, −0.214 to −0.139). The same tendency was also observed with weight and BMI. Early disease onset at younger than 1 year and persistent eczema had the strongest association with development of food allergy at age 3 years (OR, 11.794; 95% CI, 10.721–12.975). One phenotype of eczema with early-onset and persistent disease creates a risk of both physical growth impairment and development of food allergy. Infants who present with the early-onset and persistent type of eczema should be carefully evaluated daily for impaired physical growth and development of food allergy. [ABSTRACT FROM AUTHOR]

In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states. However, the contribution of sentinel immune cells (i.e. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. The pro-inflammatory cytokine interleukin 1β (IL-1β) induces the expression of chemokines, such as interleukin 8 (IL-8), in autoimmune diseases of the skin. IL-8 induces the activation and recruitment of innate immune cells such as neutrophils to the site of inflammation. IL-1β-mediated induction of IL-8 expression is important for the pathogenesis of autoimmune diseases; however, the intracellular singling remains to be understood. To elucidate the mechanism of the onset of autoimmune diseases, we established a model for IL-1β-induced dermatitis and investigated MAPK signaling pathways in IL-1β-induced IL-8 expression. We also identified that a MAP3K Tpl2 acts as an upstream modulator of IL-1β-induced ERK1/2 activation in dermal fibroblasts. We observed an increase in the expression of IL-8 mRNA and protein in cells treated with IL-1β. ERK1/2 inhibitors significantly reduced IL-1β-induced IL-8 expression, whereas the inhibitor for p38 MAPK or JNK had no effect. IL-1β induced ERK1/2 phosphorylation, which was attenuated in the presence of an ERK1/2 inhibitor. IL-1β failed to induce IL-8 expression in cells transfected with siRNA for ERK1, or ERK2. Notably, a Tpl2 inhibitor reduced IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. We confirmed that the silencing of Tpl2 in siRNA-transfected fibroblasts prevented both in IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. Taken together, our data indicate the importance of Tpl2 in the modulation of ERK1/2 signaling involved in the IL-1β-induced development of autoimmune diseases affecting the dermal tissue, such as atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults. Objective: To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort. Methods: This was a cohort study of 9,154,936 individuals aged 0–99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0–17 years), adults (18–74 years), and older adults (75–99 years). Results: Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70–0.76) and was more likely to be active (59.7%, 95% CI 59.5–59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups. Conclusion: In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0–17 and adults ages 18–74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis is a common skin disease characterized by altered cutaneous immunity in which patients often exhibit lower skin microbiota diversity compared to healthy skin and are prone to colonization by Staphylococcus aureus. Apple cider vinegar has been shown to have antibacterial effects; however, its effects on the skin microbiome have not previously been well-described. Objectives: We aimed to examine the effects of topical dilute apple cider vinegar soaks on Staphylococcus aureus abundance, skin bacterial microbiome composition, and skin bacterial microbiome diversity in atopic dermatitis participants compared to healthy skin. Methods: Eleven subjects with atopic dermatitis and 11 healthy controls were enrolled in this randomized, non-blinded, single-institution, split-arm pilot study. Subjects soaked one forearm in dilute apple cider vinegar (0.5% acetic acid) and the other forearm in tap water for 10 minutes daily. Skin bacteria samples were collected from subjects' volar forearms before and after 14 days of treatment. 16S sequencing was used to analyze Staphylococcus aureus abundance and skin bacterial microbiome composition, and alpha diversity of microbiota were determined using Shannon diversity index. Results: There was no difference in skin bacterial microbiome in atopic dermatitis subjects after 2 weeks of daily water or apple cider vinegar treatments (p = 0.056 and p = 0.22, respectively), or in mean abundance of S. aureus on apple cider vinegar-treated forearms (p = 0.60). At 2 weeks, the skin bacterial microbiomes of healthy control subjects were not significantly different from the skin bacterial microbiome of atopic dermatitis subjects (p = 0.14, 0.21, 0.12, and 0.05). Conclusions: Our results suggest that daily soaks in 0.5% apple cider vinegar are not an effective method of altering the skin bacterial microbiome in atopic dermatitis. Further studies are needed to explore the effects of different concentrations of apple cider vinegar on skin microflora and disease severity. Trial number: UVA IRB-HSR #19906. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is one of the most common skin diseases in dogs. Pathogenesis is complex and incompletely understood. Skin colonizing bacteria likely play an important role in the severity of this disease. Studying the canine skin microbiota using traditional microbiological methods has many limitations which can be overcome by molecular procedures. The aim of this study was to describe the bacterial microbiota of the skin and ear canals of healthy non-allergic and allergic German shepherd dogs (GSDs) without acute flare or concurrent skin infection and to compare both. Bacterial 16S rRNA gene amplicon sequence data revealed no differences of bacterial community patterns between the different body sites (axilla, front dorsal interdigital skin, groin, and ear canals) in non-allergic dogs. The microbiota at the different body sites of non-allergic GSDs showed no significant differences. Only for the samples obtained from the axilla the bacterial microbiota of allergic dogs was characterized by a lower species richness compared to that of non-allergic dogs and the bacterial community composition of the skin and ear canals of allergic dogs showed body site specific differences compared to non-allergic dogs. Actinobacteria was the most abundant phylum identified from the non-allergic dogs and Proteobacteria from allergic dogs. Macrococcus spp. were more abundant on non-allergic skin while Sphingomonas spp. were more abundant on the allergic skin. Forward step redundancy analysis of metadata indicated that the household the dogs came from had the strongest impact on the composition of the skin microbiome followed by sex, host health status and body site. [ABSTRACT FROM AUTHOR]

Background: Skin conditions are the fourth leading cause of nonfatal disease globally, with atopic dermatitis (AD) a major and rising contributor. Though atopic dermatitis (AD) is rising in prevalence, little is known about its psychosocial effects on children and families in low- and middle-income countries (LMICs). Methods: We conducted a community-based, cross-sectional survey of 2242 under-5 children in rural Bangladesh using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to measure AD prevalence and severity, the Patient-Oriented Eczema Measure (POEM) to measure severity, and the Infants' Dermatitis Quality of Life index (IDQoL) and Dermatitis Family Index (DFI) to measure quality of life. Findings: Overall AD prevalence in under-five children was 11.9% [95% confidence interval (CI) 10.6–13.3%]. Prevalence was highest in children age 30–35 months [16.2% (95% CI 11.4–21.0)]. IDQoL was significantly higher in males (2.67) vs. females (1.95, p = 0.015), the lowest (3.06) vs. highest (1.63) wealth quintile (p<0.001), and among mothers with < primary (2.41) vs. > secondary (1.43) education (p = 0.039). POEM severity was correlated with IDQoL (r = 0.77, p<0.001) and DFI (r = 0.56, p<0.001). Severe disease as rated by caretakers was correlated with POEM (r = 0.73, p<0.001), IDQoL (r = 0.82, p<0.001) and DFI (r = 0.57, p<0.001). Conclusions: Severe AD significantly affects quality of life for children and families in Bangladesh. As access to healthcare expands in LMICs, identification and treatment of both the medical and psychosocial morbidities associated with the disease are needed. [ABSTRACT FROM AUTHOR]

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children's Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year. [ABSTRACT FROM AUTHOR]

Investigating metabolic functional capability of a human gut microbiome enables the quantification of microbiome changes, which can cause a phenotypic change of host physiology and disease. One possible way to estimate the functional capability of a microbial community is through inferring metagenomic content from 16S rRNA gene sequences. Genome-scale models (GEMs) can be used as scaffold for functional estimation analysis at a systematic level, however up to date, there is no integrative toolbox based on GEMs for uncovering metabolic functions. Here, we developed the MetGEMs (metagenome-scale models) toolbox, an open-source application for inferring metabolic functions from 16S rRNA gene sequences to facilitate the study of the human gut microbiome by the wider scientific community. The developed toolbox was validated using shotgun metagenomic data and shown to be superior in predicting functional composition in human clinical samples compared to existing state-of-the-art tools. Therefore, the MetGEMs toolbox was subsequently applied for annotating putative enzyme functions and metabolic routes related in human disease using atopic dermatitis as a case study. Author summary: Examining the metabolic function capability of microbiome is an important step in understanding the microbe-microbe and microbe-host communication. In this study, we developed MetGEMs (metagenome-scale models) toolbox, a strategic approach to infer metabolic functions from 16S rRNA gene sequences with overall aiming at annotating metabolic functions in the human gut microbiome. During the development, MetGEMs toolbox was tested and validated with shotgun metagenomic data. At the end, we used our toolbox to identify putative enzyme functions and metabolic routes associated to atopic dermatitis from the Thailand Pediatric Allergy Research Cohort. This work highlights the importance of metagenome-scale models as crucial framework for uncovering metabolic functions and routes of human gut microbiome. [ABSTRACT FROM AUTHOR]

Clinical Practice Guidelines (CPGs) play significant roles in most medical fields. However, little is known about the extent of financial Conflicts of Interest (FCOIs) related to pharmaceutical companies (Pharma) selling dermatology prescription products and dermatology CPG authors in Japan. The aims of this study were to elucidate the characteristics and distribution of payments from Pharma to dermatology CPG authors in Japan, and to evaluate the extent of transparency and accuracy in their FCOI disclosures. We analyzed the records of 296 authors from 32 dermatology CPGs published by the Japanese Dermatological Association from the beginning of 2015 to the end of 2018. Using the payment data reported by 79 Pharma between 2016–2017 in Japan, we investigated the characteristics of the CPG authors and the payments from the Pharma to them. Furthermore, we evaluated the transparency and accuracy of the FCOI disclosures of the individual CPG authors. Of the 296 CPGs authors, 269 authors (90.6%) received at least one payment from the Pharma. The total monetary value of payments for the 2-year period was $7,128,762. The median and mean monetary value of payments from the Pharma reporting were $10,281 (interquartile range $2,796 -$34,962) and $26,600 (standard deviation $40,950) for the two years combined. Of the 26 CPG authors who disclosed FCOIs due to the monies received from Pharma, only the atopic dermatitis CPG authors and the acne vulgaris CPG authors published their potential FCOIs. In Japan, most dermatology CPG authors received financial payments from Pharma. The transparency of the CPGs, as reported by the CPG authors, was inadequate, and a more rigorous framework of reporting and monitoring FCOI disclosure is required to improve the accuracy and transparency with relation to possible Conflicts of Interest. [ABSTRACT FROM AUTHOR]

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials often suffer from significant recruitment barriers, poor adherence, and dropouts, which increase costs and negatively affect trial outcomes. The aim of this study was to examine whether making it virtual and reward-based would enable nationwide recruitment, identify patients with variable disease severity, achieve high adherence, and reduce dropouts. Methods: In a siteless, virtual feasibility study, individuals with atopic dermatitis (AD) were recruited online. During the 8-week study, subjects used their smartphones weekly to photograph target AD lesions, and completed patient-oriented eczema measure (POEM) and treatment use questionnaires. In return, subjects were rewarded every week with personalized lifestyle reports based on their DNA. Results: Over the course of the 11 day recruitment period, 164 (82% women and 18% men) filled in the form to participate, of which 65 fulfilled the inclusion criteria and signed the informed consent. Ten were excluded as they did not complete the mandatory study task of returning the DNA sample. 55 (91% women, 9% men) subjects returned the DNA sample and were enrolled throughout Denmark, the majority outside the Copenhagen capital region in rural areas with relatively low physician coverage. The mean age was 28.5 (SD ±9.5 years, range 18–52 years). The baseline POEM score was 14.5±5.6 (range 6–28). Based on the POEM, 7 individuals had mild, 28 had moderate, 17 had severe, and 3 had very severe eczema. The retention rate was 96% as 53 out of 55 enrolled completed the study. The adherence was very high, and more than 90% of all study tasks were completed. Follow up of 41 subjects showed that 90% would take part again or continue if the study had been longer. Conclusion: A virtual trial design enables recruitment with broad geographic reach and throughout the full spectrum of disease severity. Providing personalized genetic reports as a reward seems to contribute to high adherence and retention. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ), a creamy substance secreted by honeybees, is the exclusive diet for queen bee differentiation and life maintenance. RJ has been used in cosmetics, beverages, medicines, and supplements worldwide. However, allergy is a concerning issue for RJ, especially in atopic dermatitis (AD) and asthma patients. In some cases, allergic reactions are seen after the first intake of RJ, suggesting the existence of allergens cross-reactive with RJ. Information about the cross-reactive allergens is very important for the safe application of RJ; however, study of this cross-reactivity is quite limited. In this study, we attempted to identify allergens cross-reactive with RJ by using serum samples from 30 AD patients who had never been exposed to RJ. In an enzyme-linked immunosorbent assay (ELISA) experiment, RJ-binding IgE antibodies were detected in the serum of 10 out of 30 patients, and their antibody titers ranged from 4- to 2,048-fold dilution ratios. Additionally, 3 AD patients were determined to be positive in a skin-prick test (SPT) with an RJ solution. Significant correlations were observed between the anti-RJ antibody titer and nonspecific IgE and between the anti-RJ antibody titer and the Eczema Area and Severity Index score. We further examined the cross-reactivity between RJ and 14 typical allergens by using an ELISA-inhibition assay and demonstrated that the following 6 allergens showed cross-reactivity with RJ: the European house dust mite (HDM) (Dermatophagoides pteronyssinus), American HDM (Dermatophagoides farinae), snow crab (Chionocetes spp.), edible crab (Cancer pagurus), German cockroach (Blatella germanica), and honeybee venom (Apis mellifera). In conclusion, people with a history of allergic diseases, including AD, asthma, and allergic rhinitis, should be cautioned against consuming RJ products because of the potential for cross-reactive responses to ensure the safe and successful use of RJ supplements. [ABSTRACT FROM AUTHOR]

A cross-sectional hypothesis generating study was performed to investigate modifiable exposures such as whether feeding pattern (a non-processed meat based diet, NPMD, or an ultra-processed carbohydrate based diet, UPCD), certain environmental factors and their timing of exposure might be associated with the development of canine atopic dermatitis (CAD). Also, genetic and demographic factors were tested for associations with CAD. The data was collected from the validated internet-based DogRisk food frequency questionnaire in Finland. A total of 2236 dogs were eligible for the study (the owners reported 406 cases and 1830 controls). Our main interest was to analyze modifiable early risk factors of CAD, focusing on nutritional and environmental factors. We tested four early life periods; prenatal, neonatal, early postnatal and late postnatal periods. Twenty-two variables were tested for associations with CAD using logistic regression analysis. From the final models we identified novel dietary associations with CAD: the NPMD during the prenatal and early postnatal periods had a significant negative association with the incidence of CAD in adult dogs (age above 1 year). Oppositely, UPCD was associated with a significantly higher risk for CAD incidence. Other variables that were associated with a significantly lower risk for CAD were maternal deworming during pregnancy, sunlight exposure during early postnatal period, normal body condition score during the early postnatal period, the puppy being born within the same family that it would stay in, and spending time on a dirt or grass surface from 2 to 6 months. Also, the genetic factors regarding maternal history of CAD, allergy-prone breeds and more than 50% white-colored coat all showed a significant positive association with CAD incidence in agreement with previous findings. Although no causality can be established, feeding NPMD early in life seemed to be protective against CAD, while UPCD could be considered a risk factor. Prospective intervention studies are needed to establish the causal effects of the protective role of NPMD on prevalence of CAD during the fetal and early postnatal life. [ABSTRACT FROM AUTHOR]

Insect bite hypersensitivity (IBH) is a Th-2, IgE-mediated dermatitis of horses caused by bites of insects of the genus Culicoides that has common features with human atopic dermatitis. Together with Th-2 cells, the epithelial barrier plays an important role in development of type I hypersensitivities. In order to elucidate the role of the epithelial barrier and of the skin immune response in IBH we studied the transcriptome of lesional whole skin of IBH-horses (IBH-LE; n = 9) in comparison to non-lesional skin (IBH-NL; n = 8) as well as to skin of healthy control horses (H; n = 9). To study the "baseline state" of the epithelial barrier, we investigated the transcriptome of non-lesional epidermis in IBH-horses (EPI-IBH-NL; n = 10) in comparison with healthy epidermis from controls (EPI-H; n = 9). IBH-LE skin displayed substantial transcriptomic difference compared to H. IBH-LE was characterized by a downregulation of genes involved in tight junction formation, alterations in keratins and substantial immune signature of both Th-1 and Th-2 types with particular upregulation of IL13, as well as involvement of the hypoxic pathway. IBH-NL shared a number of differentially expressed genes (DEGs) with IBH-LE, but was overall more similar to H skin. In the epidermis, genes involved in metabolism of epidermal lipids, pruritus development, as well as IL25, were significantly differentially expressed between EPI-IBH-NL and EPI-H. Taken together, our data suggests an impairment of the epithelial barrier in IBH-affected horses that may act as a predisposing factor for IBH development. Moreover, these new mechanisms could potentially be used as future therapeutic targets. Importantly, many transcriptional features of equine IBH skin are shared with human atopic dermatitis, confirming equine IBH as a natural model of skin allergy. [ABSTRACT FROM AUTHOR]

Introduction: Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. Methods: We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. Results: We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7–2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4–1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9–1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3–2.7]), food (OR = 0.8, [95% CI = 0.3–2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6–2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0–4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1–2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7–16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1–8.5]), or furred animals (OR = 0.6, [95% CI = 0.5–0.9]). Conclusion: These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: Night shift work surrounding pregnancy may contribute to the risk of developing atopic diseases in offspring due to alterations in the prenatal environment, from stress. Objective: To examine the association of maternal night shift work surrounding pregnancy and offspring risk of developing atopic diseases from childhood to adolescence. Methods: We examined the association between night shift work before and during pregnancy among 4,044 mothers in the Nurses' Health Study II (NHSII) and atopic dermatitis, asthma and hay fever risk in 4,813 of their offspring enrolled in the Growing Up Today Study (GUTS). Mothers reported whether GUTS participants had ever been diagnosed with atopic dermatitis, asthma or hay fever in the GUTS Mothers' questionnaire. Generalized estimating equation regression models were used to estimate multivariable adjusted odds ratios (OR) and 95% confidence intervals (CIs). Results: There were no significant associations between pre-conception maternal night shift work and risk of atopic dermatitis, asthma or hay fever in their offspring. Among 545 mothers with information on night shift work during pregnancy, shift work also was not associated with atopic dermatitis, asthma or hay fever in the offspring. Stratified analyses by history of parental atopy and maternal chronotype showed some statistically significant findings, but they were inconsistent and no significant interaction was seen with increasing duration of night shift work. Conclusion: In this study, night shift work before and during pregnancy did not increase offspring risk of developing atopic dermatitis, asthma or hay fever. [ABSTRACT FROM AUTHOR]

Introduction: The primary purpose of crosslinking is to halt the progression of ectasia. We retrospectively assessed the condition of keratoconus patients who were followed-up at least twice after the initial examination to evaluate keratoconus progression, to identify definitive factors to predict a later need for corneal crosslinking (CXL). Methods: The medical charts of 158 eyes of 158 keratoconus patients (112 males and 46 females; mean age, 27.8 ± 11.7 years), who were followed up at the Department of Ophthalmology, Keio University School of Medicine at least twice after the initial examination to evaluate keratoconus progression were retrospectively reviewed. Best-spectacle corrected visual acuity, intraocular pressure, steepest corneal axis on the anterior float (Ks), thinnest corneal thickness according to Pentacam® HR, and corneal endothelial cell density were assessed. Gender, age, onset age of keratoconus, history of atopic dermatitis, and Pentacam® indices were also recorded. CXL was performed when the eye showed significant keratoconus progression, an increase in the steepest keratometric value, or an increase in the spherical equivalent or cylinder power of the manifest refraction by more than 1.0 D versus the respective values 2 years prior. Predictor variables and the requirement for CXL were analyzed using logistic regression. Results: Fifty-eight eyes required CXL treatment. The best predictor of the requirement for CXL was patient age, followed by the Pentacam® Rmin (the minimum sagittal curvature evaluated by Pentacam®) value. The incidence of CXL was 86.4% in the < 20 years age group, with an Rmin of ≤ 5.73 mm, whereas 10.8% in the ≥ 27 years age group with an Rmin > 5.73 mm underwent treatment. Conclusions: An age of < 20 years and an Rmin value of ≤ 5.73 mm predicted keratoconus progression and the requirement for CXL treatment in the near future. [ABSTRACT FROM AUTHOR]

Background: Dermatological services in Laos, South East Asia are limited mainly to the capital and patch testing is currently not available, so no data exists regarding the common cutaneous allergens in this population. Objectives: The aim of this study was to document common allergens in paediatric patients with atopic dermatitis attending the allergy clinic in the capital, Vientiane. Patients/Materials/Methods: Fifty paediatric patients with atopic dermatitis were patch tested using TRUE Test® panels 1 to 3 (35 allergens). Readings were taken at Days 2 and 4. Results: Twenty-six positive patch tests were recorded on Day 4 in 15 children (30%). The most common allergens were: gold (18%), nickel (10%), formaldehyde (6%) and p-Phenylenediamine (6%). Other positive allergens were potassium dichromate (2%), cobalt dichloride (2%), Bronopol (2%), paraben mix (2%), fragrance mix 1 (2%) and neomycin (2%). The majority of the patients with positive reactions were female. Conclusions: This study represents the first documented patch test results in the Lao population. It is hoped that these findings will help clinicians to advise the families of children with atopic dermatitis on common allergens to avoid and inform future work on contact dermatitis in this population. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to validate the English version of the Itch Cognition Questionnaire in a sample of patients with chronic itch due to psoriasis or atopic dermatitis. An English-language version of an instrument assessing itch-related cognitions is needed since cognitions can contribute to a worsening of itch, and chronic itch is prevalent in English-speaking counties and internationally. Methods: The German Itch Cognitions Questionnaire was translated into English, and cognitive interviewing was conducted to finalize item wording. Internal and test-retest reliability, item discrimination, responsiveness to change, and construct, convergent, and discriminant validity were assessed in a national sample of 137 individuals with chronic itch due to atopic dermatitis or psoriasis recruited online. Results: Internal reliability was high with Cronbach's alphas of 0.93 for the Catastrophizing subscale and 0.88–0.90 for Coping. The Pearson's correlation assessing 1-month test-retest reliability for the Catastrophizing subscale was r = 0.62 and for the Coping subscale was r = 0.61. The corrected item-total correlation revealed that items were relatively consistent with the scores for the subscales (with correlations ranging from 0.58 to 0.79), indicating very good item discrimination. Results of factor analysis, convergent and discriminant, and responsiveness to change analyses provided evidence for validity. Conclusions: This study showed good psychometric characteristics of the English version of the Itch Cognitions Questionnaire. We suggest that future studies investigate the use of the measure in clinical practice to assist with treatment planning and outcome assessment related to itch as well as address study limitations such as sampling and replication. [ABSTRACT FROM AUTHOR]

Background: An increased prevalence of allergies and an increased incidence of breast cancer have been observed. The hypothesis that atopy may have a protective effect against the risk of different types of breast cancer was evaluated. Methods: In this study, 11,101 patients (11,101 women with a mean age of 55.2±14.7 years) with different types of breast cancer were tested for allergies. Allergies were confirmed based on the retrospective analysis of allergy diagnostic procedures in patients who had been previously diagnosed with breast cancer. The retrospective prevalence rates of active allergic diseases, including allergic rhinitis, bronchial asthma and atopic dermatitis, were assessed. All patients were also analyzed for bronchial asthma and allergic rhinitis according to the relevant guidelines. A group of healthy control patients was used for the comparisons. Results: The women with breast cancer had a significantly lower incidence of IgE-mediated allergic diseases than the controls. The odds ratios (ORs) for allergic rhinitis, atopic dermatitis, and bronchial asthma were 0.61 (95% CI: 0.57–0.73), 0.17 (95% CI: 0.11–0.44), and 0.73 (95% CI: 0.65–0.83), respectively. The mean serum concentrations of total IgE were significantly lower in the study population of women with breast cancer than in the patients of the control group (39.2 ± 26.2 kU/L vs. 108.5 ± 38.5 kU/L; p = 0.002). Conclusion: Our results suggest that the overall incidence of allergies, especially allergic rhinitis, is lower in patients with certain types of cancer than in individuals who did not have cancer. Further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Teledermatology is a tool that provides accurate diagnosis and has been gaining more emphasis over time. It can be used for triage in primary care attention to address skin conditions improving access and reducing time to treatment for surgical, severe or even lethal diseases. Objectives: Our main goal was to evaluate the proportion of pediatric patient's lesions that could be managed using teledermatology in primary care attention. Secondly, we wanted to assess the ten most frequent skin conditions, the most common treatments and the referrals made by the teledermatologists to biopsy, in-presence dermatologist or kept at primary care attention. Methods: A cross-sectional retrospective study involving 6,879 individuals and 10,126 lesions was conducted by store-and-forward teledermatology during one year in the city of Sao Paulo, Brazil. If the photographs taken had enough quality, teledermatologist would diagnose, treat and orient each lesion (if possible), and choose one of three options for referral: direct to biopsy, in-presence dermatologist or kept at primary care attention. Results: Teledermatology managed 62% of the lesions to be kept at primary care attention, 37% were referred to dermatologists and 1% to biopsy, reducing the mean waiting time for an in-presence visit in 78%. In patients 0–2 years old, lesions related to eczema and benign congenital lesions predominated. From 3–12 years old, eczema was still a major cause of complaint, as well as warts and molluscum. From 13–19 years old, acne was the most significant problem, followed by atopic dermatitis, nevi and warts. The most frequent treatment was emollient. Conclusion: Teletriage addressed 63% of the lesions without the need for an in-presence visit, suggesting that teledermatology can manage common diseases and optimize dermatological appointments for the most serious, surgical or complex skin illnesses, reducing the mean waiting time for them. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is one of the most common childhood skin diseases that can affect the quality of life (QoL) of children. The QoL of Montenegrin children with AD has not been sufficiently explored. The aim of this study was to assess their QoL with special emphasize on age differences. Methods: This cross-sectional study included children with AD seen at the Clinic of Dermatology and Venereology, Clinical Center of Montenegro (CCM) in Podgorica between August 2017 and July 2018. The QoL was assessed with the Infants' Dermatitis Quality of Life Index (IDQOL) and the Children's Dermatology Life Quality Index (CDLQI). Disease severity was measured by the Three Item Severity (TIS) score. Results: A total of 386 children with AD aged from newborn to 16 years took part in this study. The mean total score of the QoL was 14.7 in infants (0–4 years old), 19.4 in younger children (5–9 years old), and 16.6 in older children (10–16 years old). Age was in negative correlation with the CDLQI score, leisure domain of the CDLQI and CDLQI sleep, and in positive correlation with the IDQOL child mood. TIS score was in positive correlation with both the IDQOL and CDLQI score. Conclusions: The QoL measured by CDLQI was more impaired in younger children, whilst IDQOL child mood was more impaired in older infants. The most impaired QoL was seen in children in the age group 5–9 years. Regardless of disease severity, treatment and counseling of children suffering from AD should be tailored specifically to their age. [ABSTRACT FROM AUTHOR]

The expression of thymic stromal lymphopoietin (TSLP), a cytokine which greatly contributes to the induction of type I allergy, is upregulated in chronic inflammation such as atopic dermatitis and psoriasis. As hypoxia in the epidermis is important for maintaining skin homeostasis, we examined the regulation of TSLP expression by hypoxic conditions in normal skin epithelial tissues. TNF-α-induced expression of TSLP in human keratinocyte HaCaT and in mouse keratinocyte PAM212 cell lines were inhibited under hypoxic condition (1% O2), although the mRNA expressions of TNF-α, IL-6, IL-8, MCP-1, and VEGF-A were not inhibited. Hypoxia-mimicking conditions, which include NiCl2, CoCl2, and DMOG, an inhibitor of 2-oxoglutarate-dependent enzymes, also selectively inhibited TNF-α-induced TSLP expression. These results suggested that inactivation of prolyl hydroxylase by hypoxia and hypoxia-mimicking conditions is involved in the repression of TNF-α-induced TSLP expression. Interestingly, the inhibition of TSLP production by hypoxic treatment was significantly reversed by treatment with the HIF-2α antagonist but not with the HIF-1α inhibitor. DMOG-induced inhibition of TSLP promoter activity was dependent on the -71 to +185 bp promoter region, suggesting that the binding of HIF-2 to hypoxia response element (HRE) in this region repressed the TSLP expression. These results indicated that hypoxia and hypoxia-mimicking conditions inhibited TSLP expression via HIF-2 and HRE-dependent mechanisms. Therefore, PHD and HIF-2α could be a new strategy for treatment of atopic dermatitis and psoriasis. [ABSTRACT FROM AUTHOR]

There is an error in the Funding statement. The correct Funding statement is as follows: This work was supported by the National Research Foundation of Korea funded by the Korean government (NRF-2020R1A4A1018598, NRF-2021R1A2C2006818). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors received no specific funding for this work.By In-Seon Lee; Mijung Yeom; Kyuseok Kim; Dae-Hyun Hahm; SeHyun Kang and Hi-Joon ParkReported by Author; Author; Author; Author; Author; Author [Extracted from the article]

Background: Children with atopic disease may have reduced health-related quality of life (QoL) and morning cortisol. Possible links between QoL, morning cortisol and atopic disease are unclear. We aimed to determine if QoL was associated with morning salivary cortisol at two years of age, and if asthma, atopic dermatitis and/or allergic sensitisation influenced this association. Secondarily, we aimed to determine if QoL at one year of age was associated with salivary cortisol one year later. Methods and findings: The Bronchiolitis All SE-Norway study included infants during hospitalisation for acute bronchiolitis in infancy (bronchiolitis group) and population-based control infants (controls). The present study included all 358 subjects with available Infant Toddler Quality of Life Questionnaire (ITQOL) from parents, consisting of 13 domains and morning salivary cortisol at two years of age. Answers from the same 0–100 score questionnaire, with optimal score 100 nine months after enrolment, was also available for 289 of these children at about one year of age. Recurrent bronchial obstruction was used as an asthma proxy. Atopic dermatitis was defined by Hanifin and Rajka criteria and allergic sensitisation by a positive skin prick test. Due to different inclusion criteria, we tested possible interactions with affiliation groups. Associations between QoL and cortisol were analysed by multivariate analyses, stratified by bronchiolitis and control groups due to interaction from affiliation grouping on results. At two years of age, QoL decreased significantly with decreasing cortisol in 8/13 QoL domains in the bronchiolitis group, but only with General health in the controls. The associations in the bronchiolitis group showed 0.06–0.19 percentage points changes per nmol/L cortisol for each of the eight domains (p-values 0.0001–0.034). The associations remained significant but diminished by independently including recurrent bronchial obstruction and atopic dermatitis, but remained unchanged by allergic sensitisation. In the bronchiolitis group only, 7/13 age and gender adjusted QoL domains in one-year old children were lower with lower cortisol levels at two years of age (p = 0.0005–0.04). Conclusions: At two years, most QoL domains decreased with lower salivary cortisol among children who had been hospitalised for acute bronchiolitis in infancy, but for one domain only among controls. Recurrent bronchial obstruction and to a lesser extent atopic dermatitis, weakened these associations that nevertheless remained significant. After bronchiolitis, lower QoL in one-year old children was associated with lower salivary cortisol at two years. [ABSTRACT FROM AUTHOR]