Search Results (174)

Background/Objectives: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, but its relationship with gastric cancer (GC) remains unclear. This study aimed to investigate the association between AD and GC using a nationwide Korean database. Methods: Using the Korean National Health Insurance Service-National Sample Cohort, we conducted a nested case–control study including 10,174 GC patients and 40,696 matched controls (1:4 by age, sex, income, and region). Overlap propensity score weighting was used to control for confounders. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via logistic regression. Results: AD was significantly associated with an increased risk of GC (adjusted OR = 1.08; 95% CI: 1.01–1.15). Subgroup analyses revealed stronger associations among individuals aged ≥ 65 years (OR = 1.12), men (OR = 1.10), rural residents (OR = 1.14), and those without comorbidities (CCI = 0, OR = 1.15). Higher risks were also observed in participants with non-allergic rhinitis (OR = 1.43) or no asthma (OR = 1.12). Conclusions: AD may be associated with an increased risk of GC in the Korean population. These findings may highlight the importance of considering dermatological conditions in the context of systemic cancer risk. Full article

Previously, we defined CHI3L1 and PI3 as genes related with asthma and severity by analysis of differential gene expression. In this study, we investigated the role of DNA methylation in their regulation, and their relationship with protein levels and clinical parameters. Peripheral blood mononuclear cells (PBMCs) and sera were collected from healthy controls (HCs), nonallergic asthmatic (NA), and allergic asthmatic (AA) patients. RNA and DNA were extracted from PBMCs using the trizol method. Gene expression was assessed by qRT-PCR, and DNA methylation of CpG sites near the promoters was analyzed using sodium bisulfite treatment followed by PCR amplification. DNA methylation analysis was performed using the Sequenom EpiTYPER platform. Protein levels were quantified by ELISA, and statistical analyses were carried out using GraphPad software. Consistent with previous findings, CHI3L1 and PI3 gene expression were significantly lower in asthmatic patients compared to controls. Conversely, CHI3L1 protein levels were higher in both patient groups, while PI3 protein showed no significant changes. DNA methylation analysis revealed higher overall DNA methylation percentages in NA and AA patients for both genes compared to HCs. Despite this, no significant correlations were observed between DNA methylation and gene or protein expression, although some correlations were observed with clinical parameters. In conclusion, CHI3L1 and PI3 represent potential asthma biomarkers, whose regulation may be partially influenced by DNA methylation, a mechanism more pronounced in asthmatic patients than in healthy subjects. Full article

Background: Childhood obesity is a pro-inflammatory state associated with poorer outcomes in chronic allergic diseases, such as asthma, and in adults, it is a recognized risk factor for more severe anaphylaxis. However, whether this association extends to the pediatric population remains unclear. Objectives: The aim of this study was to assess the association between nutritional status, as measured by Body Mass Index (BMI), and anaphylaxis severity and presentation in a cohort of hospitalized children. Methods: We retrospectively assessed the association between BMI categories (underweight, normal weight, overweight, and obese) and the severity (WAO grading) and clinical presentation of anaphylaxis in 199 hospitalized children (0–18 years). Results: No statistically significant association was found between BMI categories and anaphylaxis severity (χ² = 7.06, p = 0.861). Severe reactions (WAO grades 4–5) were rare across BMI categories, occurring in 0% of underweight, 3.8% of normal-weight, 9.1% of overweight, and 7.7% of obese children. In regression analyses adjusting for age, sex, asthma, and atopic dermatitis, BMI was not an independent predictor of anaphylaxis severity, whether considered as a categorical or continuous variable (all odds ratios non-significant, 95% CIs crossing 1). Similarly, organ system involvement did not differ between BMI groups (all p > 0.05). Conclusions: In this pediatric cohort, contrary to findings in adults, we did not find nutritional status to be a predictor of anaphylaxis severity or presentation. This suggests obesity’s role as a risk factor may be age-dependent and that adult data should be extrapolated to children with caution. Full article

Antioxidant mechanisms consist of both enzymatic and non-enzymatic compounds, which can be either endogenous or exogenous and play a crucial role in counteracting oxidative stress. These compounds are primarily obtained through the diet. Vegetables, plants, and fruits contain a wide range of alkaloids, polyphenols, and terpenoids, collectively referred to as “phytochemicals.” Many of these substances are responsible for the beneficial properties of fruits and vegetables, which are essential components of a healthy lifestyle, contributing to the prevention of chronic diseases and the promotion of longevity. Nutraceuticals are bioactive substances present in food—or its components—that exert positive effects on health and may help prevent or treat various disorders. In this review, we examine the main applications of nutraceuticals in allergic disorders. The literature reports numerous studies on exogenous dietary antioxidant supplementation in various allergic conditions, including bronchial asthma, atopic dermatitis, food allergies, allergic rhino-conjunctivitis, urticaria, and angioedema. In some of these conditions, promising results have been observed. These positive outcomes are generally associated with a reduction in oxidative stress markers, enhancement of antioxidant systems, and, in some cases, anti-inflammatory effects. The administration of exogenous substances through food derivatives or dietary supplements, when scientifically standardized, has been proven to be effective. However, further large-scale, unbiased studies are needed—particularly those that include a broader range of oxidative stress biomarkers. Full article

Background and Objectives: Effects of allergen exposure may be modified through endogenous and exogenous factors, resulting in heterogeneity of clinical features, time course and intensity of symptoms of allergic disease. This creates challenges in allergy diagnosis and management, yet studies addressing the variability of allergen reactivity in relation to potential modifying factors are not numerous. The aim of the study was to retrospectively analyze the frequency and profile of reactivity to inhalant allergen extracts in patients followed in a single center in the years 2017–2020, in relation to sex, age, clinical symptoms and final clinical diagnosis. Materials and Methods: This is a retrospective analysis of skin prick test (SPT) results in 1711 outpatients, performed with dust mites, pollen (alder, hazel, birch, grasses, rye, mugwort), cat, dog and Alternaria allergens. Reactivity profiles were assessed in the entire population divided into sex and age subgroups. Relationships between SPT results, age, sex and clinical diagnosis were assessed using factor analysis. Results: The highest reactivity frequencies were found for grass (60.5%), rye (57.22%), birch (47.34%), alder (42.5%) and Dermatophagoides pteronyssinus mites (41.8%). Monovalent reactivity was found mainly to mugwort (3.2%, n = 55), followed by cat and mites allergens. Reactivity to ≥1 allergen was more frequent in males. The risk of allergic rhinitis (AR) was significantly higher in subjects allergic to grass, rye, hazel and alder pollen, as compared to subjects non-sensitized to these allergens. Reactivity to perennial allergens (dog, cat and dust mites) was significantly associated with asthma diagnosis. The risk of developing atopic dermatitis was significantly associated with reactivity to birch and alder pollen. Conclusions: SPTs are a valuable tool for assessing the occurrence of atopy and allergy. Reactivity to specific aeroallergens may be associated with increased probability of development of a given atopic condition. This warrants further studies regarding the interplay between possible modifiers of allergen exposure effects. Full article

Although omalizumab is currently approved for a limited number of indications—such as asthma, chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria—its potential applications are expanding each year. Owing to its diverse and not yet fully elucidated mechanism of action, including effects on both IgE- and non-IgE-mediated hypersensitivity reactions with delayed onset, this monoclonal antibody may be beneficial in a wide range of allergic and non-allergic conditions. To date, numerous clinical trials and case reports have documented the successful off-label use of omalizumab. It appears particularly promising for patients with difficult-to-treat hypersensitivities, such as food and drug allergies, which continue to pose significant challenges in modern allergology. Even though further research is needed to establish clear indications for its use in these contexts, omalizumab holds considerable potential to enhance the outcomes and clinical efficacy of food immunotherapy and drug desensitization protocols. The aim of this review is to present the current and potential future applications of omalizumab as an adjunctive treatment in food allergy therapy and in desensitization protocols for patients with hypersensitivity to selected drugs. Full article

Asthma has traditionally been viewed as a single disease, but recent research reveals its clinical and molecular complexity. This perspective highlights the need to shift from a traditional, uniform treatment paradigm to one that embraces the heterogeneity of asthma across individuals. Each patient presents a unique clinical story shaped by a complex interplay of genetic predispositions, developmental programming during critical early-life windows, the influence of sex and hormones, and lifelong environmental exposures. Asthma comprises multiple subtypes with distinct clinical and biological features. Furthermore, lifestyle factors such as obesity and smoking, along with highly prevalent comorbidities like allergic rhinitis and gastroesophageal reflux disease, significantly modify the disease’s course and response to treatment. This article explores how classifying the disease into clinical phenotypes (observable characteristics) and molecular endotypes (underlying mechanisms)—particularly the distinction between T2-high and T2-low inflammation—provides a crucial framework for managing this complexity. The application of this framework, guided by biomarkers, has enabled the development of targeted biologic therapies that can transform care for specific patient subgroups. Despite these advances, significant challenges remain. The pathophysiology of certain subgroups, particularly non-T2 asthma, remains poorly defined, and there is an urgent need for reliable predictive biomarkers to guide therapy and monitor outcomes. It is our opinion that future studies must adopt a systems-biology strategy, with a multi-omics approach that constructs a comprehensive molecular profile of each patient. This integrative methodology will require the use of advanced computational methods, including machine learning and artificial intelligence, to decipher the complex pathways linking genetic and environmental inputs to clinical disease. In conclusion, this article argues for a more personalized understanding of asthma, urging clinicians and researchers to consider each patient’s unique clinical presentation. Full article

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

Hexokinase catalyzes the first rate-limiting step glycolysis. However, the roles of hexokinase 2 (HK2) in asthma remain incompletely understood. This study aimed to investigate metabolic alterations in asthma, focusing on the expression, function and regulation of HK2. In this study, non-targeted metabolomics analysis of 20 asthma patients and 15 healthy controls identified metabolic alterations in asthma, particularly in the glycolytic pathways. Consistently, HK2 expression was elevated in both asthma individuals and mice with allergic airway inflammation. Airway epithelium–specific HK2 knockdown and pharmacological inhibition with 2-deoxy-D-glucose (2-DG) significantly attenuated airway inflammation and hyperresponsiveness in mice induced by ovalbumin/ lipopolysaccharide. Mechanistic analyses demonstrated that HK2 regulates epithelial apoptosis and inflammation via interaction with peptidylprolyl isomerase F (PPIF), independent of voltage-dependent anion channel 1 (VDAC1). Asthma is associated with metabolic reprogramming, characterized by alterations in lipid and glucose metabolism. These findings establish HK2 plays a crucial role in asthma pathogenesis by promoting airway epithelial apoptosis and inflammation in asthma, suggesting its potential as a therapeutic target. Full article

Asthma is a chronic and heterogeneous inflammatory airway disease with diverse clinical endotypes and limited curative treatment options. Recent systems biology analyses identified four potential molecular triggers—AKT1, MAPK13, STAT1, and TLR4—as candidate regulators of asthma-associated signaling pathways. This study aimed to validate the expression of these four proteins and their downstream signaling elements in peripheral blood mononuclear cells (PBMCs) from patients with allergic asthma (AA), nonallergic asthma (NA), and healthy controls (HC), to explore their potential as biomarkers or therapeutic targets. For that, PBMC samples were collected from 45 AA patients, 17 NA patients, and 15 HC subjects. Gene and protein expression of AKT1, MAPK13, STAT1, and TLR4 were quantified using RT-qPCR and Western blotting. Expression patterns were compared across groups and stratified by asthma severity. Correlations with clinical parameters (FEV1, FVC, FeNO, IgE, eosinophil counts) and treatment regimens were also assessed. All four target genes showed significantly reduced expression in asthma patients compared to controls (p < 0.001), with the most marked downregulation in NA patients. At the protein level, MAPK13 and TLR4 showed significant differential expression. Stratification by severity revealed a stepwise reduction in gene expression in AA patients, correlating with disease severity, whereas NA patients showed uniformly low expression regardless of severity. Multiple pathway-related genes, including RELA, SMAD3, NFATC1, and ALOX5, were also downregulated, particularly in NA patients. Notably, differential correlations were observed between gene expression and lung function parameters in AA vs. NA groups. In conclusion, this study supports the potential involvement of AKT1, MAPK13, STAT1, and TLR4 in asthma pathogenesis and highlights differences between allergic and nonallergic asthma at the molecular level. These proteins and their associated pathways may serve as future targets for biomarker development or endotype-specific therapies. Further studies in larger and more diverse cohorts, including functional validation, are warranted. Full article

Background/Objectives: Recurring infections in children with allergies pose significant clinical challenges, with these conditions often exacerbating each other through complex immunological interactions. This narrative review examines the connection between recurring infections and allergic conditions in pediatric patients, focusing on how immune system dysfunction influences infection susceptibility in respiratory allergies. Methods: A comprehensive literature search across PubMed, Web of Science, and SciELO databases was conducted from January 2014 to May 2024. Studies involving children and adolescents up to 18 years old with diagnosed respiratory allergies were included, while reviews, opinion pieces, case reports, and studies not addressing immune–infection interactions were excluded. Results: Analysis reveals significant immune dysfunction in allergic children, affecting both innate and adaptive immunity components. Children with allergic rhinitis and asthma demonstrate decreased interferon-gamma production, increasing vulnerability to viral infections (particularly rhinovirus) and bacterial infections such as Mycoplasma pneumoniae. Rhinovirus represents the most common pathogen, present in 75% of asthma exacerbations. Atopic children exhibit markedly higher bacterial infection rates, with 27.1% showing Mycoplasma pneumoniae involvement versus 4.9% in non-atopic children. Conclusions: Recurring infections in allergic pediatric patients result from significant immune dysfunction involving altered cytokine production and immune cell function. These complex interactions highlight the need for targeted therapeutic approaches that enhance immune responses and reduce infection risks. Future research should focus on identifying specific biomarkers and immune mechanisms for developing more effective interventions. Full article

Asthma is a chronic and multifaceted respiratory condition that affects over 300 million individuals across the globe. It is characterized by persistent inflammation of the airways, which leads to episodes of wheezing, breathlessness, chest tightness, and coughing. The most prevalent form of asthma is classified as Type 2 or T2-high asthma. In this variant, the immune response is heavily driven by eosinophils, mast cells, and T-helper 2 (Th2) cells. These components release a cascade of cytokines, including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13). This release promotes several processes: the production of immunoglobulin E (IgE), which is integral to allergic responses; the recruitment of eosinophils—white blood cells that contribute to inflammation and tissue damage. Conversely, non-Type 2 or T2-low asthma is typically associated with a different inflammatory profile characterized by neutrophilic inflammation. This type of asthma is driven by T-helper 1 (Th1) and T-helper 17 (Th17) immune responses, which are often present in older adults, smokers, and those suffering from more severe manifestations of the disease. Among asthmatic patients, approximately 80–85% of cases are classified as T2-high asthma, while only 15–20% are T2-low asthma. Treatment of asthma focuses heavily on controlling inflammation. Inhaled corticosteroids remain the cornerstone therapy for managing T2-high asthma. For more severe or treatment-resistant cases, biologic therapies targeting specific inflammatory pathways, such as anti-IgE (omalizumab), anti-IL-5 (mepolizumab, benralizumab), and anti-IL-4/IL-13 (dupilumab), have shown great promise. For T2-low asthma, macrolide antibiotics like azithromycin and other novel therapies are being explored. This article reviews the safety, efficacy, and indications of the currently approved biologics and discusses potential novel biologics for asthma. Full article

Background/Objectives: In recent years, there has been an increase in the prevalence of eosinophilic esophagitis (EoE), in which dysphagia is one of the main symptoms. To date, there are few data on the prevalence of EoE in pediatric patients with dysphagia. The aim of this study was to determine the causes of dysphagia in children in our region. The second aim of this study was to estimate the prevalence of EoE in children with swallowing difficulties and to see if there were differences in the characteristics of dysphagia reported by children with EoE compared to children with non-EoE-related dysphagia. Methods: The 6-year retrospective analysis included patients with dysphagia who were referred to our department. Children with dysphagia were further divided into two groups: group I consisted of children with dysphagia due to EoE, while group II consisted of children with dysphagia due to other causes (non-EoE). Results: One hundred and forty-six children between the ages 0 and 17 were enrolled into the study, including thirty-seven in group I and one hundred and nine in group II. The most common causes of dysphagia were gastrointestinal diseases, followed by neurological/psychiatric disorders. The prevalence of EoE was 25.34% in the whole study group and 41.11% considering only gastrointestinal causes of dysphagia. Children in group I were more likely to have coexisting asthma, allergic rhinitis and food allergy. There was statistically significance in higher blood eosinophil count in EoE individuals. In a multivariate binominal logistic regression model, only eosinophilia and coexisting food allergy were associated with an increased risk of EoE in patients with dysphagia. Conclusions: In our study, the most common cause of dysphagia was gastroenterological diseases, especially EoE. Patients with dysphagia, comorbid allergy and peripheral blood eosinophilia should be suspected for having EoE and referred for endoscopy. Full article

Background/Objectives: The guideline on allergen-specific immunotherapy of the European Academy of Allergy and Clinical Immunology recommends subcutaneous allergen-specific immunotherapy for the treatment of allergic rhinitis in children and adults with moderate to severe symptoms. The five years cohort study described below was designed in 2020 to demonstrate non-inferiority in terms of safety, tolerability and efficacy in a paediatric population compared with adult patients treated with microcrystalline tyrosine-adsorbed allergoids for their tree and grass pollen allergy in a perennial setting. Here, we present the preliminary findings from the first year. Methods: The Combined Symptom and Medication Score was chosen as the primary endpoint of this therapy. Secondary endpoints include the Rhinoconjunctivitis Quality of Life Questionnaire, the retrospective Rhinoconjunctivitis score, the Asthma Control Test and the Rhinitis Control Test, as well as an analysis of adverse drug reactions. Results: A total number of 320 patients were enrolled into this study, with 129 of these patients in the age group between 5 and 17 years and 191 patients in the adult age group. Mean Combined Symptom and Medication Score values did not differ significantly between minors and adults in the first pollen season after treatment induction. The retrospective score showed a strong and significant reduction in rhinoconjunctivitis and asthma symptoms. Treatment was well tolerated, with more than 80% of patients reporting no adverse drug reactions. Conclusions: The validity of this study approach of a cohort study has been confirmed by this first interim analysis for the initial course of therapy in the first year. Full article