Hundreds of genetic associations for asthma have been identified, yet translating these findings into mechanistic insights remains challenging. We leveraged plasma proteomics from the UK Biobank Pharma Proteomics Project (UKB-PPP) to identify biomarkers and effectors of asthma risk or heterogeneity using genetic causal inference approaches. We identified 609 proteins associated with asthma status (269 proteins after controlling for body mass index [BMI] and smoking). Analysis of genetically predicted protein levels identified 70 proteins with putative causal roles in asthma risk, including known drug targets and proteins without prior genetic evidence in asthma (e.g., GCHFR, TDRKH, and CLEC7A). The genetic architecture of causally associated proteins provided evidence for a Toll-like receptor (TLR)1-interleukin (IL)-27 asthma axis. Lastly, we identified evidence of causal relationships between proteins and heterogeneous aspects of asthma biology, including between TSPAN8 and neutrophil counts. These findings illustrate that integrating biobank-scale genetics and plasma proteomics can provide a framework to identify therapeutic targets and mechanisms underlying disease risk and heterogeneity.

The increasing prevalence of pediatric atopic diseases in China poses substantial risks to children's physical health, mental well-being, and quality of life. Cognitive behavioral interventions for caregivers are effective in managing pediatric atopic diseases. Existing interventions are typically siloed and lack integration across the comorbidities of the atopic march. The protection motivation theory (PMT) could provide an integrated cognitive behavioral intervention framework for addressing shared pathophysiological mechanisms and unifying management strategies across atopic diseases, while online interventions offer advantages in accessibility, cost-effectiveness, and scalability, particularly for caregiver-mediated pediatric care.

This study aimed to develop and evaluate a PMT-based cognitive behavioral online (PMT-CBO) intervention for caregivers of children with atopic diseases, assessing its effects on caregivers' protective motivation, behavioral intentions, preventive practices, and children's atopic disease outcomes.

A quasi-experimental design was conducted in 3 health care institutions in Hangzhou, China, where 2 health care institutions were assigned to the PMT-CBO group (127/243, 52.3%) and 1 health care institution was assigned to the control group (116/243, 47.7%). Caregivers in the PMT-CBO group received a 4-week structured course comprising 16 online modules delivered via a WeChat mini-program, whereas controls received routine care with verbal education. Primary outcomes included caregivers' PMT dimensions (threat appraisal and coping appraisal), behavioral intentions, and preventive behaviors, and secondary outcomes involved children's symptom severity and medication adherence. The primary outcome scales or questionnaires were designed by the research team, while the secondary outcome scales were derived from established studies. All scales demonstrated good reliability and validity. Intention-to-treat analysis was used.

Compared to the control group, the PMT-CBO group demonstrated significant improvements in overall PMT scores (Z=-6.289; P<.001) and most subdimensions (response efficacy, self-efficacy, threat severity, and response cost, with P<.05), except susceptibility (Z=-1.321; P=.19) and reward appraisals (Z=-0.989; P=.32). In the intervention group, caregivers exhibited stronger intentions and partial behavioral optimization (eg, environmental allergen control, with Z=-3.025; P=.002) and children showed improved medication adherence (Z=-4.457; P<.001) and alleviated eczema (Z=-3.112; P=.002) and allergic rhinitis symptoms (Z=-3.277; P<.001), although no significant differences emerged in asthma control (Z=-.830; P=.41) or food allergy-related caregiver burden (Z=-1.693; P=.09).

The PMT-CBO intervention enhanced caregivers' motivation and intentions and children's medication adherence and eczema and rhinitis outcomes, with a 91.3% (116/127) completion rate via WeChat's scalable platform. Limited improvements in asthma control and food allergy management implied the future need for additional condition-specific plug-ins, beyond the core PMT-CBO modules. Moreover, merging this PMT-CBO intervention with implementation techniques or ecological frameworks could help address intention-behavior gaps and external barriers, thereby promoting equitable and precision-based allergy care.

Cow's milk protein allergy (CMPA) is early life's most common food allergy. There is limited data on the development of respiratory allergies in childhood for infants with CMPA.

This study aimed to evaluate the development of respiratory allergic diseases in childhood according to the mechanism of CMPA in patients with CMPA in the first two years of life.

Patients who were diagnosed with CMPA in the first two years of life and were over five years old during the study period were included in the study. The sociodemographic, clinical, and laboratory data of patients were recorded, and the status of respiratory allergic disease development in patients was assessed using the ISAAC questionnaire.

A total of 301 patients were included in the study; 182 (60.5%) were male. Most of the patients had mixed-type (87;28.9%) and had non-IgE-mediated (n:87;28.9%) CMPA. Of CMPA cases, 27.9% developed doctor-diagnosed asthma and 31.2% developed doctor-diagnosed allergic rhinitis. Doctor-diagnosed asthma was observed mostly with IgE-mediated CMPA (n:30;37%), and doctor-diagnosed allergic rhinitis was observed mostly with non-IgE-mediated CMPA (n:32;36.8%), and these differences were not statistically significant (p = 0.094, p = 0.385). Also, maternal asthma increased the risk of doctor-diagnosed asthma, while parental consanguinity, allergic rhinitis in mother/sibling, and paternal eczema were risk factors for doctor-diagnosed allergic rhinitis.

In this study, 27.9% of patients with CMPA in the first two years of life developed doctor-diagnosed asthma, and 31.2% developed allergic rhinitis. There was no difference in the frequency of occurrence based on the mechanism of CMPA development.

Over the past decades, atopic diseases have emerged as a growing global health concern. The Global Report on Atopic Dermatitis 2022 estimated that approximately 223 million people worldwide were living with atopic dermatitis in 2022, with around 43 million being children or adolescents. The financial burden associated with the treatment of this condition poses a significant challenge for both healthcare systems and patients. The current therapeutic approach for atopic diseases primarily focuses on symptomatic management, aiming to mitigate the effects of an overactive immune system. The most widely used treatments include topical or systemic corticosteroids, which suppress inflammation, and emollients, which help restore the skin barrier function. However, prolonged corticosteroid use is associated with adverse effects, including impaired immune response and reduced ability to combat external and internal threats. Consequently, there is a growing interest in developing alternative therapeutic strategies for managing atopic dermatitis. Among these emerging treatments, hyperbaric oxygen therapy (HBOT) appears particularly promising. HBOT has a beneficial effect on the vascular and immune systems, which results in improved functioning of tissues and organs. This therapy has demonstrated efficacy in promoting wound healing, particularly in conditions such as thermal burns and diabetic foot ulcers. Given these properties, HBOT is being tested as a potential adjunctive therapy for atopic dermatitis and other allergy-related diseases. In this paper, we present the current state of knowledge regarding the application of HBOT in the treatment of atopic and immune-mediated conditions, with a focus on its immunomodulatory and regenerative effects.

Increased blood levels of inorganic arsenic compounds (iAs) are associated with the onset of allergic diseases. This study investigated the direct relationship between oral exposure to iAs and the onset of several allergic diseases. A mouse model of type 1, 2, and 17 helper T cell (Th1, Th2, and Th17) dependent allergies was generated in female BALB/c mice by topical treatment with 2,4-dinitrochlorobenzene, toluene-2,4-diisocyanate, and imiquimod. Several concentrations of iAs (0, 0.3, 1, 3, and 10 mg/kg) were administered orally for 3 or 4 days during each allergen challenge. Itch behavior and changes in skin thickness were monitored, the animals were euthanized, and inflammatory responses in the auricular lymph nodes and skin were analyzed. The influence of subacute oral exposure to iAs (0.3 and 3, and 24-52 days) on the development of chronic Th2 allergy was examined using mouse models of TDI-induced atopic dermatitis and Dermatophagoides farinae-induced asthma. Acute oral exposure to iAs significantly exacerbated Th2- and Th17-dependent allergies, whereas Th1-dependent allergic reactions were not significantly influenced. The influence of iAs exposure on Th2- and Th17-dependent allergy development was corroborated by subacute oral exposure to low concentrations of iAs in a chronic model of Th2 allergy. Symptoms and immune reactions were significantly increased following iAs exposure. Our findings imply that oral exposure to inorganic arsenic significantly affects the pathology of a mouse model of Th2- and Th17-dependent allergy development, but not a Th1-dependent allergy.

Background: Chronic pruritus and inflammatory skin lesions, characterized by high recurrence, are hallmarks of atopic dermatitis (AD). Despite its increasing prevalence, the development of therapeutic agents for AD remains limited. This study aimed to evaluate the therapeutic effects of deep sea minerals (DSMs) in mist and cream formulations on the development of AD-like skin lesions in NC/Nga mice exposed to either Dermatophagoides farinae body extract (Dfb) or 2,4-dinitrochlorobenzene (DNCB). Methods: To induce AD, 100 mg of Biostir AD cream containing crude Dfb or 200 µL of DNCB (1%) was topically applied to the dorsal skin of NC/Nga mice. Additionally, 200 µL of deep sea mineral mist (DSMM) and 10 mg of deep sea mineral cream (DSMC) were applied daily to the dorsal skin for 4 weeks. AD was assessed through visual observations, clinical scoring of skin severity, serological tests, and histological analysis. Results: Visual and clinical evaluations revealed that DSMs inhibited the formation of AD-like skin lesions. DSMs also significantly affected trans-epidermal water loss and erythema. Treatment with DSMs resulted in reduced serum levels of IgE, IFN-γ, and IL-4. Histological analysis indicated that DSMs decreased skin thickness. Immunostaining for the CD4 antigen demonstrated a reduced infiltration of CD4+ T cells, which drive the Th2 response in AD, following DSM treatment. Conclusions: In conclusion, the cream formulation of DSMs showed better results than the mist formulation. These results suggest that DSMs may be an effective treatment for AD-like skin lesions, especially in cream formulation.

Triclosan, a common antimicrobial agent, is widely used in personal-care products and as a topical antiseptic in atopic dermatitis (AD).

This study aimed to evaluate the topical and systemic effect of triclosan on AD in murine models, with a specific focus on the role of thymic stromal lymphopoietin (TSLP).

AD-like skin disease was induced by topical application of MC903 and house dust mites in female wildtype BALB/c, C57BL/6 J, and TSLP receptor (TSLPR)-knockout mouse strains. Mice were treated with triclosan both topically and systemically. Skin inflammation was assessed by measuring ear thickness. Infiltration of immune cells was analyzed by flow cytometry and immunohistochemistry (IHC). Cytokine expression was determined by quantitative real-time PCR.

Triclosan application induced skin inflammation in a dose-dependent manner. Topical triclosan treatment increased ear inflammation and immune cell infiltration in AD-like mouse models. Systemic administration of triclosan also enhanced local AD-like skin reactions. Triclosan-induced skin inflammation was reduced in TSLP-receptor-knockout mice or by blocking TSLP, thus indicating the pivotal role of TSLP in mediating the immunological effects of triclosan.

Topical and systemic administration of triclosan exacerbates AD-like skin inflammation in murine models, with TSLP being a central mediator of this process. The translational relevance of these findings to human disease remains uncertain, as no direct human data are available.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by relapsing and remitting episodes. Although AD is well-known for its association with other allergic conditions, its relationship with Meniere's disease has not been thoroughly investigated. This study aimed to explore the potential correlation between AD and Meniere's disease.

This study utilized data from the National Health Insurance Service-National Sample Cohort, a nationwide population-based database. The AD group was selected from a cohort of 1 million individuals randomly extracted from database. A non-AD group was obtained through Propensity Score Matching.

The AD group comprised 84,579 individuals, with an equal number of individuals in the non-AD (control) group. The overall hazard ratio (HR) for Meniere's disease in the AD group was 1.44 (95% confidence interval (CI): 1.31-1.6). Subgroup analysis showed an adjusted HR of 0.42 (95% CI: 0.38-0.48) for Meniere's disease in males, 4.99 (95% CI: 4.45-5.62) in the middle-aged group (40-59 years), and 8.21 (95% CI: 7.21-9.35) in the older age group (≥60 years). Additionally, the adjusted HRs for developing Meniere's disease were higher in patients with comorbidities, including allergic rhinitis (1.18 [95% CI, 1.07-1.32]), allergic contact dermatitis (1.32 [95% CI, 1.19-1.48]), and allergic conjunctivitis (1.54 [95% CI, 1.32-1.82]).

Long-term follow-up revealed that the prevalence of Meniere's disease was 1.44 times higher in the AD group compared to the control group. Moreover, older age, female sex, allergic rhinitis, allergic contact dermatitis, and allergic conjunctivitis were identified as factors that increase the risk of developing Meniere's disease.

3 Laryngoscope, 135:1478-1485, 2025.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition, affecting 15%-20% of children and up to 10% of adults. It has a significant impact on patients' quality of life and represents a considerable burden on healthcare systems. Management strategies aim to restore the skin barrier, reduce inflammation, and achieve physiological and homeostatic balance. This study evaluates the safety and efficacy of a new dermocosmetic formulation combining poly-l-lysine biovectors with vitamins A and C.

A single-arm, open-label study was conducted on 20 patients diagnosed with AD, including 14 women and 6 men aged between 24 and 63, with skin phototypes of Fitzpatrick I-VI. Treatment involved sequential application of poly-l-lysine G2/vitamin C in the morning and poly-l-lysine G3/vitamin A in the evening for 28 days, on the face, hands, and body. Outcomes were assessed using the Dermatology Life Quality Index (DLQI) and SCORAD scores. Additional assessments included a visual analog scale for pruritus and sleep disturbance, as well as patient self-report questionnaires on skin improvement and treatment satisfaction.

The treatment was well-tolerated, with no adverse effects and no relapses of AD. After 28 days, patients showed a significant reduction in DLQI (-61.8%, Cohen's d = 1.20) and SCORAD (-41.8%, Cohen's d = 1.05) scores. Objective improvements included reductions in erythema (-50%), dryness (-60%), and pruritus (-50%).

This study demonstrates the potential of poly-l-lysine-based dermocosmetics combined with vitamins A and C to improve the symptoms and quality of life of patients suffering from AD. The formulations were well-tolerated and effective in restoring the skin barrier and reducing inflammation. Further large-scale controlled studies are needed to validate these results and explore long-term efficacy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, immune dysregulation, and compromised skin barrier function. Although there are some reports that indicate a link between AD and chronic kidney disease (CKD), the prevalence and underlying mechanism of the association between AD and CKD are still unclear. We aimed to clarify the mechanism underlying the association between AD and CKD using an AD-like mouse model.

Human serum and urine samples from adults in the U.S. were analyzed using data from the National Health and Nutrition Examination Survey (NHANES). An AD-like mouse model was established by repeatedly applying 2,4-dinitrochlorobenzene to the backs and ears of the mice. Kidney inflammation and podocyte function were evaluated via PAS and H&E staining, immunofluorescence staining, and electron microscopy.

We found that compared to healthy subjects in the NHANES cohort study, patients with AD had altered kidney function. AD-like model mice exhibited albuminuria and renal dysfunction one to three months after the induction of AD. In addition, there were remarkable decreases in triglyceride and very-low-density lipoprotein levels and increases in low-density lipoprotein and non-high-density lipoprotein levels in AD-like model mice. After histological staining of the kidneys of AD-like model mice, macrophage and neutrophil infiltration was detected, and the foot process effacement of podocytes was observed via electron microscopy. In addition, the gene expression of slit diaphragm- and podocyte-related proteins such as nephrin, podocin, and synaptopodin decreased, whereas the gene expression of inflammatory mediators such as S100A8 and S100A9 increased.

Following improvements in skin inflammation, alleviation of albuminuria, renal dysfunction and dyslipidemia were observed. These findings suggest that AD-related cutaneous inflammation is associated with albuminuria and podocyte dysfunction.

Atopic dermatitis (AD) is the most common inflammatory skin disease in the pediatric age group, affecting 15%-20% of children globally. Initial treatment modes include hydration, occlusive topical medicines, antimicrobial treatment, phototherapy, and systemic immune suppressants in the case of severe to moderate refractory AD. However, there is a lack of head-to-head studies on the choice of topical and systemic therapies for moderate to severe AD in the pediatric age group.

This systematic review aimed to determine the efficacy and safety of topical and systemic treatments for moderate-to-severe AD in the pediatric age group.

A systematic review was performed following the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. A search of articles was done from PubMed and Google Scholar from 1975 to 2023.

We found a total of 1114 possible clinical trials. Of these, 68 articles fulfilled the eligibility criteria. Thirty-four articles discussed topical therapies, which included corticosteroids, calcineurin inhibitors, and emollients, and 34 articles were about systemic therapies, consisting of cyclosporine, dupilumab, upadacitinib, thymopentin, omalizumab, antihistamines, probiotics, and others. Out of 68 studies, 41 were randomized controlled trials.

Based on the study results, we conclude that topical steroids and calcineurin inhibitors are effective and safe in mild to moderate pediatric AD. It was also demonstrated that while systemic monotherapy with dupilumab (in age groups younger than 6 months) and JAK inhibitors (like abrocitinib and upadacitinib in those younger than 12 years) is highly effective in rapidly reducing severity scores, their high cost and limited availability restrict their use in countries like India. In such settings, cyclosporine (and sometimes oral prednisolone in tapering doses over 2 weeks) is still recommended as a first-line therapy in severe AD while planning for steroid-sparing agents.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition that significantly impairs patients' quality of life as a result of intense itching and persistent eczematous lesions. Although AD has a multifaceted etiology-including genetic predisposition, environmental triggers, barrier dysfunction, and dysregulated immune responses-interleukin-4 (IL-4) has a recognized central role in its pathogenesis. This narrative review explores the role of IL-4 in the pathophysiology of AD, its contribution to the atopic march, and the therapeutic impact of IL-4 inhibition. IL-4 plays a critical role in skin barrier dysfunction, dysbiosis, pruritus, and inflammation, all of which contribute to the debilitating symptoms of AD. Moreover, IL-4 is implicated in other atopic conditions, such as asthma, allergic rhinitis, and food allergies, underscoring its role beyond AD and its importance in the atopic march. Recent advances in targeted therapies, particularly IL-4/IL-13 signaling inhibitors, have changed AD management. Dupilumab, an IL-4 receptor antagonist, has demonstrated significant efficacy in reducing AD symptoms and enhancing patient outcomes in both children and adults. In addition to symptomatic relief, suppressing IL-4 signaling may also offer potential for disease modification, altering AD's progression and possibly preventing the onset of other atopic conditions. This review highlights the crucial role of IL-4 as a therapeutic target in AD. By understanding the role of IL-4 in AD pathogenesis and exploring the therapeutic implications of targeting IL-4 pathways, this work can contribute to guide future research concerning treatment approaches and also emphasize the need for early and targeted interventions to mitigate disease impact and ultimately improve patient quality of life.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant implications for patient quality of life and a well-documented association with the atopic march. Recent advancements in biomarker research have unveiled critical insights into AD pathogenesis, diagnosis, prognosis, and therapeutic monitoring. This comprehensive review evaluates the utility of emerging biomarkers, including cytokines, chemokines, genetic markers, and microbiome-related components, in understanding the disease mechanisms and stratifying patient care. The role of minimally invasive diagnostic techniques, such as tape stripping and RNA monitoring, is highlighted, offering innovative approaches to pediatric populations. Furthermore, this review explores the biomarkers that predict disease progression, therapeutic response, and comorbidities, including food allergies and asthma. Personalized treatment strategies based on endotype-specific biomarkers are discussed as a future direction for improving clinical outcomes. Despite promising findings, the integration of biomarkers into routine practice necessitates further validation through large-scale studies. This work underscores the transformative potential of biomarker-driven approaches in enhancing the management of AD in children and its associated conditions.

To investigate the main characteristics of HDM-induced allergic diseases in children and to explore allergen component-specific sensitization patterns, features, and correlations with clinical symptoms.

Serum samples were collected from children with HDM-induced allergic diseases. Information on age, sex, and clinical symptoms was recorded. A protein chip method was used to detect specific IgE (sIgE) against HDM components, including Der p 1, Der f 1, Der p 2, Der f 2, Der p 5, Der p 7, Der p 10, Der p 21, and Der p 23.

116/120 (96.67%) exhibited positive reactions to HDM components. The highest positive rates were for Der p 1 (95.83%) and Der f 1 (95.83%), followed by Der p 2 (86.67%), Der f 2 (85.83%), and Der p 23 (62.50%). Der p 5, 7, and 23 positivity increased with age. Notably, Der p 23 positivity was higher in the allergic asthma (AA) group than in the non-AA, atopic dermatitis (AD), and allergic rhinitis (AR) groups and higher in AR with AA than AR-only. Der p 2 and Der f 2 had higher positive rates in respiratory allergies than in AD alone. The impact of other HDM components on different allergic diseases was minimal. Pearson correlation analysis demonstrated strong positive correlations between sIgE concentrations for various HDM components, especially between Der p 2 and Der f 2 (r = 0.96, p < 0.01).

Der p 1, Der f 1, Der p 2, Der f 2, and Der f 23 are the major allergens, with Der p 5, 7, and 23 showing age-specific sensitization patterns. Der p 2 and Der f 2 are closely associated with respiratory allergies, whereas Der p 23 is particularly linked to the development of asthma. There is a general positive correlation among the sIgE concentrations of various HDM components.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex relationship to allergens. While AD itself is not an allergic reaction and does not necessarily involve allergen sensitization, AD patients show higher rates of sensitization to food and inhalant allergens compared to the general population. Recent evidence refining the "dual allergen exposure hypothesis" demonstrates that early oral exposure to allergens through an intact gastrointestinal barrier typically promotes tolerance, while exposure through compromised skin or respiratory barriers often leads to sensitization. Therefore, the impaired skin barrier function in AD patients increases the risk of transcutaneous sensitization and may interfere with oral tolerance development. Interestingly, AD patients' sensitivity to contact allergens (such as metals and fragrances) is not necessarily higher than that of the general population, which may be related to the inherent properties of these allergens. Personalized allergen testing can help guide appropriate allergen avoidance and reintroduction strategies in AD management. The insights into optimal allergen exposure conditions have also expanded the potential applications of allergen-specific immunotherapy in preventing AD onset in high-risk populations and halting the atopic march.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.

Flare patterns are not routinely considered in the severity classification or in clinical decision-making of atopic dermatitis (AD), but frequent or severe flares may contribute considerably to the disease burden.

To characterize patients with AD in relation to their flare pattern and compare flare patterns to disease severity, life quality and treatment satisfaction.

Patients with AD from the Danish Skin Cohort were included if they had active AD with and available data on number of flare-ups within the last 12 months. Categorical variables were presented as frequencies and percentages, whereas numerical variables were presented as median and interquartile ranges (IQR). Between-group differences were tested with chi-squared tests.

A total of 1557 patients were included, with 57 reporting 0 flares, 698 (1-5 flares), 324 (6-10 flares) and 478 reporting >10 flares during the past 12 months. Both the severity measured by PO-SCORAD and the impairment of life quality measured by DLQI were higher among patients with more flares (median [IQR] PO-SCORAD: 13.0 [5.6-22.3], 29.7 [20.8-40.6], 36.3 [26.7-47.6]and 42.9 [30.7-55.6], respectively for the four flares strata, and median [IQR] DLQI: 1.0 [0.0-2.0], 3.0 [1.0-7.0], 4.0 [1.8-9.0] and 7.0 [3.0-11.0]). Satisfaction with the current treatment was generally higher among patients with no flares. However, 36.8%, 24.6% and 23.7% of patients with 1-5, 6-10 and >10 flares reported being extremely or very satisfied with their current treatment.

Patients with many flares often report a higher severity and impairment of life quality compared to patients with fewer flares. Information on flaring could benefit treatment decisions, thereby decreasing undertreatment of patients with mild AD but severe flaring.

Despite advances in our understanding of their diagnosis and treatment, pediatric allergies impose substantial burdens on affected children, families, and healthcare systems. Further, the prevalence of allergic diseases has dramatically increased over the past half-century, leading to additional concerns and concerted efforts to identify the origins, potential predictors and preventions, and therapies of allergic diseases. Together with the increase in allergic diseases, changes in lifestyle and early-life environmental influences have corresponded with changes in colonization patterns of the infant gut microbiome. The gut microbiome plays a key role in developing the immune system, thus greatly influencing the development of allergic disease. In this review, we specifically highlight the importance of the proper maturation and composition of the gut microbiome as an essential step in healthy child development or disease progression. By exploring the intertwined development of the immune system and microbiome across pediatric allergic diseases, we provide insights into potential novel strategies for their prevention and management.

Introduction: The shaping of the human intestinal microbiota starts during the intrauterine period and continues through the subsequent stages of extrauterine life. The microbiota plays a significant role in the predisposition and development of immune diseases, as well as various inflammatory processes. Importantly, the proper colonization of the fetal digestive system is influenced by maternal microbiota, the method of pregnancy completion and the further formation of the microbiota. In the subsequent stages of a child's life, breastfeeding, diet and the use of antibiotics influence the state of eubiosis, which determines proper growth and development from the neonatal period to adulthood. The literature data suggest that there is evidence to confirm that the intestinal microbiota of the infant plays an important role in regulating the immune response associated with the development of allergic diseases. However, the identification of specific bacterial species in relation to specific types of reactions in allergic diseases is the basic problem. Background: The main aim of the review was to demonstrate the influence of the microbiota of the mother, fetus and newborn on the functioning of the immune system in the context of allergies and asthma. Methods: We reviewed and thoroughly analyzed the content of over 1000 articles and abstracts between the beginning of June and the end of August 2024. Over 150 articles were selected for the detailed study. Results: The selection was based on the PubMed National Library of Medicine search engine, using selected keywords: "the impact of intestinal microbiota on the development of immune diseases and asthma", "intestinal microbiota and allergic diseases", "the impact of intrauterine microbiota on the development of asthma", "intrauterine microbiota and immune diseases", "intrauterine microbiota and atopic dermatitis", "intrauterine microbiota and food allergies", "maternal microbiota", "fetal microbiota" and "neonatal microbiota". The above relationships constituted the main criteria for including articles in the analysis. Conclusions: In the present review, we showed a relationship between the proper maternal microbiota and the normal functioning of the fetal and neonatal immune system. The state of eubiosis with an adequate amount and diversity of microbiota is essential in preventing the development of immune and allergic diseases. The way the microbiota is shaped, resulting from the health-promoting behavior of pregnant women, the rational conduct of the medical staff and the proper performance of the diagnostic and therapeutic process, is necessary to maintain the health of the mother and the child. Therefore, an appropriate lifestyle, rational antibiotic therapy as well as the way of completing the pregnancy are indispensable in the prevention of the above conditions. At the same time, considering the intestinal microbiota of the newborn in relation to the genera and phyla of bacteria that have a potentially protective effect, it is worth noting that the use of suitable probiotics and prebiotics seems to contribute to the protective effect.

Atopic dermatitis (AD) is a chronic skin inflammatory ailment commonly observed in young children and adults. Various therapeutic modalities are already explored for mitigation of AD but for prolong application very few modalities are recommended. Considering these challenges, we have successfully developed gliclazide-loaded hydrogels using the physical dispersion method. For preclinical assessment, we developed a DNCB induced an AD-like phenotype in mice, characterized by increased dermatitis index, scratching interval, ear thickness and weight, spleen and lymph node enlargement, mast cell infiltration, and elevated oxidative stress. However, topical application of the GLZ hydrogel significantly improved these DNCB-induced symptoms. Mice treated with the GLZ hydrogel exhibited a marked reduction in inflammatory markers in histological evaluations. Specifically, there was a decrease in epidermal thickness and mast cell infiltration compared to the DNCB + Vehicle group. Additionally, the topical GLZ hydrogel attenuated the AD-like phenotype by reducing oxidative stress markers. Importantly, these therapeutic effects occurred without significantly affecting blood glucose levels, highlighting the safety of the topical GLZ hydrogel. These findings demonstrate the potential of GLZ-loaded hydrogels as an effective and safe topical treatment for alleviating the symptoms of AD by targeting oxidative stress and inflammation.

Inborn errors of immunity (IEIs), also known as primary immunodeficiencies, are a group of genetic disorders affecting the development and function of the immune system. While IEIs traditionally present with recurrent infections, an increasing number of cases manifest with early-onset severe atopy, including atopic dermatitis, food allergies, asthma, and allergic rhinitis-features that are often overlooked. This can lead to delayed diagnosis and treatment, which is crucial for IEI patients due to the risk of severe infections. We conducted a literature search and reviewed all IEIs that can present with early-onset severe atopy. The hallmark features of these disorders often include early-onset, persistent, and severe atopic dermatitis, food allergies, and recurrent episodes of asthma, which may be refractory to treatments. Additionally, we discuss the importance of recognizing such severe atopy as a potential indicator of an underlying immune deficiency, particularly when accompanied by unusual infections, growth failure, or autoimmunity. This review aims to raise awareness of this association and emphasize the need for early diagnosis and genetic testing in patients with atypical or treatment-resistant allergic diseases, allowing for more timely diagnosis of underlying immunodeficiencies and appropriate treatments.

Identification of predictive biomarkers is crucial for formulating preventive interventions and halting the progression of atopic march. Although controversial, the use of accessible markers to predict or detect early onset of atopic diseases is highly desirable. Therefore, this study aimed to investigate whether corneal squamous cell carcinoma antigen-1 (SCCA1) collected from infants can predict the development of atopic dermatitis and food allergy.

This prospective study enrolled 117 infants aged 2 months (55 female and 62 male infants). The participants were monitored to evaluate the occurrence of eczematous changes at several time points, and stratum corneum samples were obtained. The association of corneal SCCA1 with the development of atopic dermatitis and food allergy in the first 3 years of life was evaluated using univariate and multivariate logistic regression.

The corneal SCCA1 level was significantly higher in children who developed atopic dermatitis than in children who did not (cheek at 2 months: 1653.06 ± 178.48 ng/mg vs. 786.95 ± 101.59 ng/mg, P = 0.0033). The corneal SCCA1 level was also significantly higher in children who developed food allergy than in children who did not (perioral skin at 2 months: 2567.31 ± 408.09 ng/mg vs. 1120.85 ± 188.49 ng/mg, P = 0.0018).

The findings suggest that non-invasive measurements of corneal SCCA1 at 2 months of age is useful for predicting atopic dermatitis and food allergy in infants at risk for atopic dermatitis and subsequent food allergy.

Atopic dermatitis (AD) is a common, chronic skin disorder that can significantly impact the quality of life (QoL) of affected individuals as well as their families. Although the pathogenesis of the disorder is not yet completely understood, it appears to result from the complex interplay between defects in skin barrier function, environmental and infectious agents, and immune dysregulation. There are no diagnostic tests for AD; therefore, the diagnosis is based on specific clinical criteria that take into account the patient's history and clinical manifestations. Successful management of the disorder requires a multifaceted approach that involves education, optimal skin care practices, anti-inflammatory treatment with topical corticosteroids, topical calcineurin inhibitors (TCIs) and/or phosphodiesterase-4 (PDE-4) inhibitors, the management of pruritus, and the treatment of skin infections. Systemic immunosuppressive agents may also be used, but are generally reserved for severe flare-ups or more difficult-to-control disease. Newer systemic agents, such as Janus Kinase (JAK) inhibitors and biologics, have a more favourable safety and efficacy profile than the older, traditional systemic immunosuppressives. Topical corticosteroids are the first-line pharmacologic treatments for AD, and evidence suggests that these agents may also be beneficial for the prophylaxis of disease flare-ups. Although the prognosis for patients with AD is generally favourable, those patients with severe, widespread disease and concomitant atopic conditions, such as asthma and allergic rhinitis, are likely to experience poorer outcomes. Newer systemic agents have been approved which are greatly improving the QoL of these patients.

Wildfires are becoming more frequent and intense on a global scale, raising concerns about their acute and long-term effects on human health. We conducted a systematic review of the current epidemiological evidence on wildfire health risks and a meta-analysis to investigate the association between wildfire smoke exposure and various health outcomes. We discovered that wildfire smoke increases the risk of premature deaths and respiratory morbidity in the general population. Meta-analysis of cause-specific mortality and morbidity revealed that wildfire smoke had the strongest associations with cardiovascular mortality (RR: 1.018, 95% CI: 1.014-1.021), asthma hospitalization (RR: 1.054, 95% CI: 1.026-1.082), and asthma emergency department visits (RR: 1.117, 95% CI: 1.035-1.204) in the general population. Subgroup analyses of age found that adults and elderly adults were more susceptible to the cardiopulmonary effects of wildfire smoke. Next, we systematically addressed the toxicological mechanisms of wildfire smoke, including direct toxicity, oxidative stress, inflammatory reactions, immune dysregulation, genotoxicity and mutations, skin allergies, inflammation, and others. We discuss wildfire smoke risk mitigation strategies including public health interventions, regulatory measures, and personal actions. We conclude by highlighting current research limitations and future directions for wildfire research, such as elucidating the complex interactions of wildfire smoke components on human health, developing personalized risk assessment tools, and improving resilience and adaptation strategies to mitigate the health effects of wildfires in changing climate.

Introduction: Iron deficiency (ID) has been intricately linked with various inflammatory diseases. Chronic rhinitis stands as one of most common respiratory inflammation disorders in children. This study aimed to investigate the prevalence of ID among preschool children with chronic rhinitis and to explore the association between ID and chronic rhinitis in this population. Methods: This cross-sectional study included children aged 3 to 7 years diagnosed with chronic rhinitis. ID was defined as transferrin saturation <20%, with absolute ID being defined as ferritin <15 ng/mL. Logistic regression analyses were performed to identify factors associated with ID. Results: A total of 72 children with chronic rhinitis were included, revealing a prevalence of ID of 47.2%. Only 5.9% children with ID exhibited absolute ID. Multivariate analysis revealed that neutrophils (odds ratio [OR] = 1.205, 95% confidence interval [CI] = 1.013-1.433, P = 0.035) and monocytes (OR = 1.803, 95% CI = 1.198-2.713, P = 0.005) were independently and significantly associated with ID. Conclusion: This study revealed a notable prevalence of ID in the preschool children with chronic rhinitis. The significant association between neutrophils and monocytes with ID implied an intricate involvement of innate immunity in the manifestation of ID.

Human skin is colonized with skin microbiota that includes commensal bacteria, fungi, arthropods, archaea and viruses. The composition of the microbiota varies at different anatomical locations according to changes in body temperature, pH, humidity/hydration or sebum content. A homeostatic skin microbiota is crucial to maintain epithelial barrier functions, to protect from invading pathogens and to interact with the immune system. Therefore, maintaining homeostasis holds promise to be an achievable goal for microbiome-directed treatment strategies as well as a prophylactic strategy to prevent the development of skin diseases, as dysbiosis or disruption of homeostatic skin microbiota is associated with skin inflammation. A healthy skin microbiome is likely modulated by genetic as well as environmental and lifestyle factors. In this review, we aim to provide a complete overview of the lifestyle and environmental factors that can contribute to maintaining the skin microbiome healthy. Awareness of these factors could be the basis for a prophylactic strategy to prevent the development of skin diseases or to be used as a therapeutic approach.

JAK-STAT signalling pathway was discovered more than quarter century ago. The JAK-STAT pathway protein is considered as one of the crucial hubs for cytokine secretion which mediates activation of different inflammatory, cellular responses and hence involved in different etiological factors. The various etiological factors involved are haematopoiesis, immune fitness, tissue repair, inflammation, apoptosis, and adipogenesis. The presence of the active mutation V617K plays a significant role in the progression of the JAK-STAT pathway-related disease. Consequently, targeting the JAK-STAT pathway could be a promising therapeutic approach for addressing a range of causative factors. In this current review, we provided a comprehensive discussion for the in-detail study of anatomy and physiology of the JAK-STAT pathway which contributes structural domain rearrangement, activation, and negative regulation associated with the downstream signaling pathway, relationship between different cytokines and diseases. This review also discussed the recent development of clinical trial entities. Additionally, this review also provides updates on FDA-approved drugs. In the current investigation, we have classified recently developed small molecule inhibitors of JAK-STAT pathway according to different chemical classes and we emphasized their synthetic routes, biological evaluation, selectivity, and structure-activity relationship.

OX40/OX40L are costimulatory molecules in the tumor necrosis factor superfamily. Numerous studies have shown that OX40/OX40L are involved in immune regulation, especially in the proliferation and differentiation of T cells and the generation of memory T cells, which play important roles in allergic diseases. In recent years, the use of OX40/OX40L as therapeutic targets for treating T-cell-mediated diseases has attracted the interest of scholars. This paper reviews the role of OX40/OX40L in allergic diseases and the progress in clinical treatments targeting this signaling pathway.

Atopic dermatitis is characterized by scratching and a TH2-dominated local and systemic response to cutaneously encountered antigens. Dendritic cells (DCs) capture antigens in the skin and rapidly migrate to draining lymph nodes (dLNs) where they drive the differentiation of antigen-specific naive T cells.

We sought to determine whether non-T-cell-derived IL-4 acts on skin-derived DCs to promote the TH2 response to cutaneously encountered antigen and allergic skin inflammation.

DCs from dLNs of ovalbumin (OVA)-exposed skin were analyzed by flow cytometry and for their ability to polarize OVA-specific naive CD4+ T cells. Skin inflammation following epicutaneous sensitization of tape-stripped skin was assessed by flow cytometry of skin cells and real-time quantitative PCR of cytokines. Cytokine secretion and antibody levels were evaluated by ELISA.

Scratching upregulated IL4 expression in human skin. Similarly, tape stripping caused rapid basophil-dependent upregulation of cutaneous Il4 expression in mouse skin. In vitro treatment of DCs from skin dLNs with IL-4 promoted their capacity to drive TH2 differentiation. DCs from dLNs of OVA-sensitized skin of Il4-/- mice and CD11c-CreIl4rflox/- mice, which lack IL-4Rα expression in DCs (DCΔ/Δll4ra mice), were impaired in their capacity to drive TH2 polarization compared with DCs from controls. Importantly, OVA-sensitized DCΔ/Δll4ra mice demonstrated impaired allergic skin inflammation and OVA-specific systemic TH2 response evidenced by reduced TH2 cytokine secretion by OVA-stimulated splenocytes and lower levels of OVA-specific IgE and IgG1 antibodies, compared with controls.

Mechanical skin injury causes basophil-dependent upregulation of cutaneous IL-4. IL-4 acts on skin DCs that capture antigen and migrate to dLNs to promote their capacity for TH2 polarization and drive allergic skin inflammation.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

In the current study, we evaluated whether atopic dermatitis (AD) affects the entire body rather than being limited to skin barrier damage and inflammation. We hypothesized that medium-term exposure of distant organs to systemic inflammatory cytokines in sub-chronic inflammatory skin diseases has detrimental effects on distant tissues.

Our findings demonstrated the dysregulation of genes and pathways associated with inflammation and the skin barrier, as well as genes and pathways involved in muscle development that respond to chemicals or stress in muscle tissues, all of which were reversed by hydrocortisone (Hc) administration. The expression of Ces1d showed significant differences during disease onset and after treatment in both skin and skeletal muscle, suggesting that Ces1d is likely responsible for the alleviation of subchronic AD.

Using NC/Nga mice with AD-like symptoms, we compared the transcriptomes of the skeletal muscle (a tissue that is relatively distant from the skin) with those of the skin (the lesion induction site) before and after disease induction, after which Hc was administered. Although further study is needed to better understand the effects of Ces1d on AD, skeletal muscle was associated with AD pathogenesis, and AD-like symptoms appeared to affect the body in a systemic manner. Given the importance of evidence-based medicine and the development of precision medicine, our findings provide insights into the mechanisms of AD onset and progression.

Atopic dermatitis (AD) is a chronic inflammatory skin condition influenced by various factors, such as the skin microbiome and metabolome. However, specific contributions of these factors to scalp involvement in AD still need to be explored. In this study, we aimed to assess the associations between the skin microbiome and metabolome in AD patients with scalp dermatitis and healthy controls (HCs).

A total of 20 AD patients with scalp involvement and 16 HCs were recruited, and their skin samples were collected for analysis. Bioinformatic analysis and 16S rRNA metagenomic sequencing were performed, with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) conducted for AD-associated skin metabolites. Spearman correlation analysis was used to identify the correlations between AD-associated skin bacteria and metabolites.

The results revealed significant differences in bacterial taxa and metabolites between the lesional and non-lesional scalp skin samples of AD patients (groups LS and NL, respectively) and those of HCs (group HC). Notably, group LS showed a significantly increased relative abundance of the genus Staphylococcus and a decreased abundance of Cutibacterium compared to group HC. The reduced abundance of Cutibacterium was also observed when comparing LS to NL. The GC-TOF-MS analysis identified 33 significantly decreased metabolites and 17 significantly increased metabolites in groups LS and NL compared with group HC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that amino acid-related metabolism was significantly altered in the metabolic pathway between groups LS, NL, and HC. Furthermore, Spearman correlation analysis showed significant correlations of the altered bacteria genera and skin metabolites between the 3 groups.

The results of this research provide valuable insights into the associations the skin microbiome and metabolome between groups LS, NL, and HC. Identifying these specific contributions may offer new avenues for understanding the pathogenesis of scalp involvement in AD patients and potentially lead to improving management strategies.

Atopic dermatitis (AD) is a highly burdensome inflammatory skin condition affecting nearly one-quarter of the pediatric population and often continuing into adulthood. Despite recent advancements in systemic therapies providing temporary symptom relief over the past decade, AD frequently remains difficult to control, necessitating increased dosages or alternative treatments due to recurrent disease. This review synthesizes current literature to identify unmet needs of treating AD beyond medication-related limitations and evaluates existing therapies for their efficacy in modifying underlying disease mechanisms. Key findings include variability in AD pathophysiology and phenotypes across different age groups and ethnicities, indicating a need for research into endotype-specific treatments. The literature also comprises evidence suggesting that select current drugs, such as targeted biologics and Janus Kinase (JAK) inhibitors, may offer long-term disease-modifying benefits. Future management strategies should explore novel approaches, including manipulation of the microbiome, immune response, and neural function, as these may lead to additional improvements in AD treatment and long-term symptom relief.

Atopic diseases, including atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR) are closely related to inflammatory diseases involving different body sites (i.e. the skin, airway, and digestive tract) with characteristic features including specific IgE to allergens (so-called "atopy") and Th2 cell-mediated inflammation. It has been recognized that AD often precedes the development of other atopic diseases. The progression from AD during infancy to FA or asthma/AR in later childhood is referred to as the "atopic march" (AM). Clinical, genetic, and experimental studies have provided evidence that allergen sensitization occurring through AD skin could be the origin of the AM. Here, we provide an updated review focusing on the role of the skin in the AM, from genetic mutations and environmental factors associated with epidermal barrier dysfunction in AD and the AM to immunological mechanisms for skin sensitization, particularly recent progress on the function of key cytokines produced by epidermal keratinocytes or by immune cells infiltrating the skin during AD. We also highlight the importance of developing strategies that target AD skin to prevent and attenuate the AM.

Allergy is a complex array of diseases influenced by innate and adaptive immunity, genetic polymorphisms, and environmental triggers. Atopic dermatitis is a chronic inflammatory skin disease characterized by barrier defects and immune dysregulation, sometimes leading to asthma and food allergies because of the atopic march. During atopic skin inflammation, Langerhans cells and dendritic cells (DCs) in the skin capture and deliver allergen information to local lymph nodes. DCs are essential immune sensors coordinating immune reactions by capturing and presenting antigens to T cells. In the context of allergic responses, DCs play a crucial role in instructing two types of helper T cells-type 2 helper T (Th2) cells and follicular helper T (TFH) cells-in allergic responses and IgE antibody responses. In skin sensitization, the differentiation and function of Th2 cells and TFH cells are influenced by skin-derived factors, including epithelial cytokines, chemokines, and signalling pathways to modify the function of migratory DCs and conventional DCs. In this review, we aim to understand the specific mechanisms involving DCs in allergic responses to provide insights into the pathogenesis of allergic diseases and potential therapeutic strategies.

While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined.

To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls.

Flow cytometry was used to measure B-cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate-to-severe AD and age-matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometry panel were used to determine frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgEs) levels were measured using ImmunoCAP®.

Adolescents with AD had lower frequencies of major B-cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL-17-producing T-cells and B-cell subsets, most significantly non-switched memory (NSM) B-cells (r = .41, p = .0005). AD severity positively correlated with a list of B-cell subsets (p < .05). IL-9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls.

Multiple correlations between B-cells and T-cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B-cell signature during adolescence, with concurrent allergen sensitization and IL-9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march.