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Immunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non–IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.

Indoor conditions contribute to allergen sensitization and multiple allergens reactivity, mainly for inhaled allergens. This study analyzes if Skin Prick Test (SPT) combined with efficient individual biomedical guidance about allergy development’s social, biological, and environmental aspects can yield a better clinical state with therapeutic implications for atopic individuals with high indoor permanence. We recruited atopic and non-atopic volunteers (clinically and in vitro diagnosed) with indoor permanence above 15 h per day and without previous SPT evaluation. The SPT and serum anti-allergen IgE analyses were performed individually in person, demonstrated, and discussed by the practitioners. Six months after, SPT and specific IgE titers determination were repeated, and a questionnaire to evaluate the effectiveness of the practitioner’s orientation was performed. After six months, 14% of atopic volunteers reported changes in their social habits, 30% said that they avoid the development of allergies clinical symptoms, and 68% reported a substantial improvement in their health after being informed mentored about their allergen reactivity. The control non-atopic group, as expected, reported no changes in social habits, the maintenance of total avoidance of allergic symptoms, and almost no improvement of their health. Reduced SPT and serum allergen-specific IgE titers were detected in the atopic individuals corroborating with questionnaire results. Our results indicated that SPT, followed by an individual and efficient discussion about the main biomedical aspects of allergy development, could exert a pronounced therapeutic role in allergy development by high indoor permanence individuals.

Pneumonia is a kind of inflammatory disease characterized by pathogen infection of lower respiratory track. Lipopolysaccharide (LPS) is the main bioactive component of Gram-negative bacteria responsible for inflammatory response. Recently, coniferyl aldehyde (CA) has been reported to play a crucial role because of its anti-inflammatory activity. However, the effect and mechanisms of CA in ameliorating symptoms of acute pneumonia remain unknown. Evaluating and identifying the value and exploring the mechanisms of CA on LPS-mediated WI-38 apoptosis and inflammation were the aims of this study. Here, CCK-8 cell viability assay was applied on WI-38 after treatment with or without LPS at different doses of CA to verify that CA can increase LPS-induced cell viability. Then, quantitative polymerase chain reaction (qPCR) and enzyme-linked-immunosorbent serologic assays (ELISA) suggested that LPS treatment dramatically decreased the expression level of IL-10 (anti-inflammatory factor) while strikingly increasing the expression levels of IL-1β, IL-6, and TNF-α (tumor necrosis factor-α; proinflammatory factor) whereas CA treatment attenuates LPS-induced inflammation of WI-38. Further, flow cytometry and Western blot assay verified that LPS treatment dramatically promoted apoptosis of WI-38 cells, while administration of CA notably inhibited apoptosis of WI-38 cells. Moreover, the Western blot assay hinted that CA could inactivate LPS-induced JAK2–STAT1 signaling pathway. These findings indicated that CA could alleviate LPS-mediated WI-38 apoptosis and inflammation injury through JAK2–STAT1 pathway in acute pneumonia.

Objective: Although there is no consensus regarding the etiology of paranasal mucous retention cysts (MRCs) in the literature, several studies suggest an allergic etiology. This study aimed to investigate a potential association between paranasal MRCs diagnosed with MRI scans and allergic sensitization in the pediatric population. Materials and Methods: A total of 4559 MRI scans were retrospectively evaluated for MRC in patients who presented to the pediatric neurology outpatient clinic with headache complaints. Fifty children with MRI findings conclusive for paranasal MRC and 50 children without such findings were included in the study. All study and control patients were invited for atopy/allergy evaluation. Total IgE measurements, blood eosinophil levels, nasal smear and skin prick tests were performed to evaluate the allergic status of the children. In addition, an allergic rhinitis symptom questionnaire was administered. Results: The mean age was 13.0±2.8 years (median 14 y, range 6-18 y) with a female-to-male ratio of 1.4:1 in the study group. The prevalence of MRC was found to be 1.1% (50 in 4559). The two groups did not differ with regard to the frequency of blood eosinophilia, nasal eosinophilia, serum IgE levels, and allergic rhinitis symptom severity (p>0.05). Positive skin test for at least one of the allergens tested was more common in the MRC group than the controls (40% vs. 16%, p=0.007). Multivariate analysis identified that a positive skin prick test for at least one allergen was a significant independent predictor of MRC (OR, 4.6; 95% CI 1.2-17.0, p=0.023). Conclusion: Our study showed that paranasal MRCs were significantly more frequent in atopic children compared to controls. Additionally, MRCs were found to be strongly associated with allergic sensitization. Keywords: Cysts, allergic rhinitis, children, diagnostic tests, signs and symptoms

Die Global Initiative for Asthma (GINA) hat in den Jahren 2019–2021 einige substanzielle Änderungen für das Management von Patienten mit Asthma empfohlen, die auch Schulkinder und Jugendliche betreffen. Eine sehr wesentliche neue Empfehlung ist, dass kurzwirksame Betamimetika (SABA) aus Sicherheitsgründen nur mehr in Kombination mit inhalativen Steroiden (ICS) gegeben werden sollten. Bei Jugendlichen werden GINA-Stufe 1 und 2 zusammengezogen und bei Asthmaproblemen eine Bedarfsinhalation mit niedrig dosierter ICS-Formoterol-Kombination empfohlen. Als Alternative wird die Trennung in Stufe 1 mit Inhalation von SABA und einem ICS bei Bedarf und in Stufe 2 wie bisher die tägliche Inhalation eines ICS und SABA bei Bedarf empfohlen. Dieser Weg wird auch als der bevorzugte bei Kindern von 6 bis 11 Jahren vorgeschlagen. Diese neuen GINA-Empfehlungen wurden jedoch nicht von allen nationalen oder internationalen Leitlinien übernommen, da vor allem für Kinder die Evidenz dafür gering ist. Tiotropium, Mepolizumab und Dupilumab wurden in die Therapie des schweren Asthmas aufgenommen. Kinder mit Asthma erkranken nicht häufiger oder schwerer an COVID-19 als Kinder ohne Asthma. Verschiedene Mechanismen wie ein möglich protektiver Effekt der Typ-2-Inflammation, die antivirale und immunmodulierende Wirkung von ICS und die Niederregulierung von ACE2-Rezeptoren durch die allergische Sensibilisierung könnten dafür verantwortlich sein.

People who live in highly allergenic regions have a greater risk of being sensitized; therefore, these areas have a higher prevalence of mono and polysensitized patients. The aim of the present study was to investigate the allergen sensitization profiles in patients with asthma in an agricultural zone in Mexico.An analytical cross-sectional study was conducted in a secondary care hospital in Obregon City, Mexico. The allergen sensitization pattern profiles were analyzed through a skin prick test (SPT) in 294 patients. Data was collected before SPT: asthma control was classified according to the Global Initiative for Asthma Criteria, nutritional status was assessed with the Body Mass Index (BMI) using Quetelet's index (BMI = weight/heightIn this study, in a group of adults with asthma, the prevalence of sensitization was 77%. The most frequent categories of aeroallergens were in indoors, in zones with weeds and abundant trees. A low proportion of monosensitized patients (2%) was observed. House dust mites were the most common allergens.Our study describes the sensitization pattern among asthma patients. This study will help identify the panel of most common allergens in this region of Mexico, and aid in selection of specific treatment through immunotherapy.

Systemic contact dermatitis (SCD) is a generalized reactivation of type IV hypersensitivity skin diseases in individuals with previous sensitization after a contact allergen is administered systemically. Patients with SCD may consider their dermatitis unpredictable and recalcitrant since the causative allergens are difficult to find. If a patient has a pattern of dermatitis suggestive of SCD but fails to improve with conventional treatment, SCD should be taken into consideration. If doctors are not familiar with the presentations of SCD and the possible routes of allergen sensitization and exposure, the diagnosis of SCD may be delayed. In this work, we summarized all of the routes through which allergens can enter the body and cause SCD, including oral intake, local contact (through skin, inhalation, nasal spray and anal application), implants, and other iatrogenic or invasive routes (intravenous, intramuscular, intraarticular, and intravesicular). This will provide a comprehensive reference for the clinicians to identify the culprit of SCD.

Background Skin prick tests are widely used to diagnose allergic sensitization. The influence of obesity on the skin prick test result has not been clearly established, even though the association between allergic disease and obesity is relatively well known. Objective To determine whether a change in body mass index (BMI) contributes to skin reactivity to histamine and allergens in a skin prick test, we performed a 2-year follow-up study on Korean children. Methods Skin prick tests for common aeroallergens were performed on elementary school students from Jeju Island, Korea. BMI was calculated using weight and height after measuring both, and demographic characteristics were surveyed. The same tests were repeated after 2 years. Results The sensitization rate increased during the 2 years between tests and the children’s mean BMI also increased, along with their age. The wheal sizes induced by Dermatophagoides pteronyssinus, Dermatophagoides farinae, Japanese cedar, and histamine were significantly increased during 2 years; however, only the histamine reaction associated with increased BMI had statistical significance. Furthermore, other variables—including the number of sensitized allergens—were not related to histamine skin reactivity. Conclusion Histamine skin reactivity increased in children over time and some allergens showed increased specific reactions; however, BMI gain is a specific predictor of histamine reactivity. Further studies are needed to elucidate the clinical significance of these changes.

Background Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood. Objectives We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma. Methods We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma. Results Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress–related metabolites. There were no significant associations between metabolites and allergic sensitization. Conclusions We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.

Asthma exacerbations are major contributors to disease morbidity in patients of all ages. To develop strategies that reduce the disease burden from exacerbations, it is helpful to review current concepts about the risk factors for asthma attacks and current approaches for prevention and treatment. Multiple factors contribute as risks and to the development of asthma exacerbations, including allergic and infectious processes. Viral respiratory infections, primarily from rhinoviruses, are the dominant exacerbating cause for most asthma patients. Allergic sensitization and allergen exposure contribute directly and enhance susceptibility for respiratory viral infections. Respiratory viruses infect airway epithelium to promote underlying type 2 inflammation with eosinophils, the predominant cellular component of increased inflammation. Deficiencies of antiviral interferon responses and generation have been identified that increase susceptibility to viral infections in asthma. Exacerbation treatment focuses on reducing airflow obstruction and suppressing inflammation, followed by improving long-term asthma control. Increasing concern exists regarding the side effects associated with frequent systemic corticosteroid use. A major advance has been the selective use of biologics to prevent exacerbations, primarily in patients with existing type 2 inflammation. Future research to prevent exacerbations is being directed toward antiviral activity and a more encompassing regulation of underlying airway inflammation.

Background Chemokines are important mediators in immune cell recruitment, contributing to allergy development. However, extensive studies of chemokines in the circulation in relation to the presence and development of allergic diseases remain scarce. Our aim was to investigate associations of circulating allergy-related chemokines with the development of asthma and sensitization cross-sectionally and longitudinally in a population-based cohort. Methods The chemokines CCL17, CCL22, CXCL10, CXCL11 and CCL18 were measured in plasma samples from children in the Manchester Asthma and Allergy Study. Samples were available from cord blood at birth (n = 376), age 1 (n = 195) and age 8 (n = 334). Cross-sectional and longitudinal association analyses were performed in relation to asthma and allergic sensitization, as well as allergic phenotype clusters previously derived using machine learning in the same study population. Results In children with asthma and/or allergic sensitization, CCL18 levels were consistently elevated at 1 and/or 8 years of ages. In a longitudinal model including information on asthma from 4 time points (5, 8, 11 and 16 years of ages), we observed a significant association between increasing CCL18 levels at age 1 and a higher risk of asthma from early school age to adolescence (OR = 2.9, 95% CI 1.1-7.6, p = .028). We observed similar associations in longitudinal models for allergic sensitization. Asthma later in life was preceded by increased CXCL10 levels after birth and decreased CXCL11 levels at birth. Conclusion Elevated CCL18 levels throughout childhood precede the development of asthma and allergic sensitization. The Th1-associated chemokines CXCL10 and CXCL11 also associated with the development of both outcomes, with differential temporal effects. Funding Agencies|MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MR/L012693/1, MR/K002449/2, MR/S025340/1]; Manchester Biomedical Research Centre (BRC); Swedish Research CouncilSwedish Research CouncilEuropean Commission [2016-01698]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [20140321]; Cancer and Allergy Foundation; Foundation Samariten; Ellen, Walter and Lennart Hesselman foundation

Background: Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta₂-agonist in this clinical scenario. Objective: To study post hoc the short-term (up to 2 months) efficacy of inhaled beta2-agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. Methods: The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2–4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. Results: Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group × treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). Conclusions: In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.

In the last decade, significant research has been focused on Toll-like reseptors (TLRs) in the pathogenesis of respiratory diseases. The presented data show that TLR-mediated signaling can be directed both at the successful alleviation of the inflammatory reaction in the respiratory tract, and at its development and aggravation. Asthma is a chronic inflammatory disease of the respiratory tract caused by genetic factors, allergens, or microbial agents. TLRs play an important role in the pathogenesis of asthma. TLRs recognize a wide range of microbial molecules, endogenous molecules, and air allergens and modulate the allergic sensitization. An important feature of TLRs is their participation in the development of an immune response to viral and bacterial infections that cause severe exacerbations of asthma. TLRs are expressed on hematopoietic and non-hematopoietic airway cells, which play an immunomodulatory role in the development of asthma when activated by TLRs agonists. Due to the involvement of TLRs in innate and adaptive immunity and the ability to regulate adaptive Th-response, these receptors are currently being used as possible targets for drug development. Therefore, understanding the mechanisms and ways in which TLRs are involved in the pathogenesis of asthma may suggest new strategies for controlling the disease.

Physicians still have great difficulty in diagnosing asthma. Over- and under diagnosis both occur for this lung disease from which around 300 million people suffer worldwide.1 For diagnosing asthma, after careful history taking, lung function testing is considered the most relevant investigation. However, other parameters could also assist in completing the asthma jigsaw. Since atopy is one of the predisposing factors for asthma, measurement of specific IgE (sIgE) could be of assistance. This statement only applies to sIgE and not to total IgE measurement, which cannot be used as crucial evidence for allergy diagnosis.2.

Background: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods: From the Scandinavian antenatally recruited PreventADALL mother–child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA/L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA/L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Results: Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16–0.81 kUA/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53–8.68). Conclusion: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and

Background Diagnostic tests for allergy rely on detecting allergen‐specific IgE. Component‐resolved diagnostics incorporate multiple defined allergen components to improve the quality of diagnosis and patient care. Objective To develop a new approach for determining sensitization to specific allergen components that utilizes fluorescent protein tetramers for direct staining of IgE on blood basophils by flow cytometry. Methods Recombinant forms of Lol p 1 and Lol p 5 proteins from ryegrass pollen (RGP) and Api m 1 from honeybee venom (BV) were produced, biotinylated, and tetramerized with streptavidin‐fluorochrome conjugates. Blood samples from 50 RGP‐allergic, 41 BV‐allergic, and 26 controls were incubated with fluorescent protein tetramers for flow cytometric evaluation of basophil allergen binding and activation. Results Allergen tetramers bound to and activated basophils from relevant allergic patients but not controls. Direct fluorescence staining of Api m 1 and Lol p 1 tetramers had greater positive predictive values than basophil activation for BV and RGP allergy, respectively, as defined with receiver operator characteristics (ROC) curves. Staining intensities of allergen tetramers correlated with allergen‐specific IgE levels in serum. Inclusion of multiple allergens coupled with distinct fluorochromes in a single‐tube assay enabled rapid detection of sensitization to both Lol p 1 and Lol p 5 in RGP‐allergic patients and discriminated between controls, BV‐allergic, and RGP‐allergic patients. Conclusion Our novel flow cytometric assay, termed CytoBas, enables rapid and reliable detection of clinically relevant allergic sensitization. The intensity of fluorescent allergen tetramer staining of basophils has a high positive predictive value for disease, and the assay can be multiplexed for a component‐resolved and differential diagnostic test for allergy., Fluorescent recombinant allergen tetramers specifically bind to and activate basophils from patients allergic to bee venom (Api m 1) and ryegrass pollen (Lol p 1 and Lol p 5). Staining intensities of recombinant Api m 1 and Lol p 1 tetramers have greater positive predictive values for allergy than basophil activation. A single flow cytometric stain with multiple allergen tetramers can be applied as a rapid component‐resolved and differential diagnostic test for allergy. Abbreviation: Strep, streptavidin

Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE). We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens. We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p

Food allergies have been rising in prevalence since the 1990s, imposing substantial physical, psychosocial, and economic burdens on affected patients and their families. Until recently, the only therapy for food allergy was strict avoidance of the allergenic food. Recent advances in translational studies, however, have led to insights into allergic sensitization and tolerance. This article provides an overview of cutting-edge research into food allergy and immune tolerance mechanisms utilizing mouse models, human studies, and systems biology approaches. This research is being translated and implemented in the clinical setting to improve diagnosis and reduce food allergy's public health burden.

SummaryIron deficiency is associated with atopy. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both allergic children and adults are more likely to have iron deficiency anemia. Immunologically, iron deficiency leads to activation of antigen-presenting cells, promotion of Th2 cells and enables antibody class switch in B cells. In addition, iron deficiency primes mast cells for degranulation, while an increase in their iron content inhibits their degranulation. Many allergens, especially those with lipocalin and lipocalin-like protein structures, are able to bind iron and either deprive or supply this trace element to immune cells. Thus, a local induced iron deficiency will result in immune activation and allergic sensitization. However, lipocalin proteins such as the whey protein β‑lactoglobulin (BLG) can also transport micronutrients into the defense cells (holo-BLG: BLG with micronutrients) and hinder their activation, thereby promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holo-BLG as a supplementary balanced diet, leading to a reduction in symptom burden. Supplementation with holo-BLG specifically supplied defense cells with micronutrients such as iron and therefore represents a new dietary approach to compensate for functional iron deficiency in allergy sufferers.

INTRODUCTION Vitamin D has known effects on the immune system, and its deficiency has been associated with allergen sensitization. MATERIAL AND METHODS A retrospective study was performed to evaluate the association between 25(OH)vitamin D (25(OH)D) and specific IgE for the most frequent allergens in our area in children and adolescents. All subjects under 15 years of age with a determination of Phadiatop® or Phadiatop Infant® and close serum 25(OH)D determination were included, from 2012 to 2019. From this sample, demographic and analytical variables were collected: specific IgE to Dermatophagoides pteronyssinus; dog and cat dander; grass, olive, and pellitory pollens; egg white; and cow milk; as well as complete blood count analysis and immunoglobulins. RESULTS A total of 749 subjects were recruited. Clusters according to deficiency, insufficiency, or sufficiency of 25(OH)D showed an association with age, Phadiatop® , D. pteronyssinus, cat and dog dander specific IgE, and a higher frequency of positive allergen sensitization (P

There is global concern regarding the harmful impact of polluted air on the respiratory health of patients with asthma. Multiple epidemiologic studies have shown ongoing associations between high levels of air pollution and poor early life lung growth, development of allergic sensitization, development of asthma, airway inflammation, acutely impaired lung function, respiratory tract infections, and asthma exacerbations. However, studies have often yielded inconsistent findings, and not all studies have found significant associations; this may be related to both variations in statistical, measurement, and modeling methodologies between studies as well as differences in the concentrations and composition of air pollution globally. Overall, this variation in findings suggests we still do not fully understand the effects of ambient pollution on the lungs and on the evolution and exacerbation of airway diseases. There is clearly a need to augment epidemiologic studies with experimental studies to clarify the underlying mechanistic basis for the adverse responses reported and to identify the key gaseous and particle-related components within the complex air pollution mixture driving these outcomes. Some progress toward these aims has been made. This article reviews studies providing an improved understanding of causal pathways linking air pollution to asthma development and exacerbation. The article also considers potential strategies to reduce asthma morbidity and mortality through regulation and behavioral/pharmacologic interventions, including a consideration of pollutant avoidance strategies and antioxidant and/or vitamin D supplementation.

BACKGROUND: Children with atopic dermatitis (AD) are often sensitized to food and aeroallergens, but sensitization patterns have not been analysed with biologic measures of disease pathogenicity. OBJECTIVE: We sought to define allergen sensitization grouping(s) using unbiased machine learning and determine their associations with skin filaggrin (FLG) and transepidermal water loss (TEWL) (assesses skin barrier integrity), S100A8 and S100A9 expression (assesses skin inflammation) and AD severity. METHODS: We studied 400 children with AD in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort to identify groupings of food and aeroallergen sensitizations. MPAACH is a paediatric AD cohort, aged 1–2, recruited through hospital/community settings between 2016 and 2018. We analysed these groupings' associations with AD biomarkers: skin FLG, S100A8 and S100A9 expression, total IgE, TEWL and AD severity. RESULTS: An unbiased machine learning approach revealed five allergen clusters. The most common cluster (N = 131), SPT(PEP,) had sensitization to peanut, egg and/or pets. Three low prevalence clusters, which included children with allergen sensitization other than peanut, egg or pets, were combined into SPT(Other). SPT(NEG) included children with no sensitization(s). SPT(PEP) children had higher median non-lesional TEWL (16.9 g/m(2)/h) and IgE (90 kU/L) compared with SPT(OTHER) (8.8 g/m(2)/h and 24 kU/L; p = .01 and p < .001) and SPT(NEG) (9 g/m(2)/h and 26 kU/L; p = .003 and p < .001). SPT(PEP) children had lower median lesional (0.70) and non-lesional (1.09) FLG expression compared with SPT(OTHER) (lesional: 0.9; p = .047, non-lesional: 1.78; p = .01) and SPT(NEG) (lesional: 1.47; p < .001, non-lesional: 2.21; p < .001). There were no differences among groupings in S100A8 or S100A9 expression. CONCLUSIONS AND CLINICAL RELEVANCE: In this largely clinic-based cohort of young children with AD, allergic sensitization to peanut, egg, cat or dog was associated with more severe disease and skin barrier function but not markers of cutaneous inflammation. These data need replicating in a population-based cohort but may have important implications for understanding the interaction between AD and allergic sensitization.

Background Atopic diseases, such as atopic dermatitis (AD) and food allergy (FA), have increased in prevalence in industrialized countries during the past few decades and pose a significant health burden. They appear to have a common underlying mechanism and a natural disease progression. AD is generally the first atopic disease to manifest followed by other atopic diseases, such as FA, allergic rhinitis, or allergic asthma suggesting that they are likely different manifestations of the same disease. Body Evidence suggests that allergic sensitization occurs through an impaired skin barrier, while consumption of these foods at an early age may actually result in tolerance. This has been termed the Dual-Allergen-Exposure hypothesis. Loss of barrier integrity has been hypothesized to enable penetration of allergens, pollutants, and microbes and initiation of an inflammatory immune cascade of events leading to sensitization. The immune dysfunction is thought to further exacerbate the impaired skin barrier to form a vicious cycle. There is much interest in preventing or protecting the skin barrier from developing a proinflammatory atopic state, which may potentially lead to the development of AD and subsequently, FA. Conclusion Research on preventing or treating skin barrier dysfunction is ongoing. A number of studies have evaluated the efficacy of emollients in preventing AD and FA with mixed results. Studies have differed in the study design, population characteristics, emollients type, and frequency, duration, and area of application. Emollient type has varied widely from oils, creams, petrolatum-based lotions, and trilipid creams. Current research is directed towards the use of trilipid emollients that are similar to the skin’s natural lipid composition with a 3:1:1 ratio of ceramides, cholesterol and free fatty acids and a pH that is similar to that of skin to determine their effectiveness for skin barrier repair and prevention of AD and FA.

Background/Aims: Recent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We eval uated the association between metabolic parameters and allergic sensitization in the elderly. Methods: We analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using an thropometric indices and serum biomarkers such as fasting glucose, lipid, adi ponectin, and RBP-4. Results: Among the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed sig nificant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index. Conclusions: RBP-4 positively associated with atopy in the general elderly popula tion irrespective of other metabolic markers.

With the increase in pet keeping among families in China, there has been a corresponding increase in the incidence of allergic diseases such as bronchial asthma and allergic rhinoconjunctivitis. Pet allergies pose important social and health problems, making their management in children crucial. There is an increasing trend of sensitization to cat and dog dander among Chinese children. The process underlying allergic sensitization is complex and is associated with an IgE-mediated type I hypersensitivity reaction that involves the upregulation of type 2 T-helper (Th2) cells, resulting in Th2 immunity. Compared with traditional serum-specific IgE (sIgE) and skin tests, molecular diagnosis may be better at predicting the progression of diseases. The association between pet keeping and allergic diseases in children remains controversial. Although the hygiene hypothesis is widely accepted in Chinese children, exposure to pets in early life remains a risk factor for allergies. Pet avoidance and allergy immunotherapy (AIT) are recommended for children with pet allergies. However, pet avoidance is difficult to maintain, and AIT is not widely available in China. There is an imbalance between the increase in allergic diseases and the shortage of prevention and treatment options. We hope that advancements in medicine, diagnosis, and healthcare policies will help resolve this issue.

Atopic dermatitis (AD) is a severe inflammatory skin disease. Langerhans cells and inflammatory dendritic epidermal cells (IDEC) are located in the epidermis of AD patients and contribute to the inflammatory processes. Both express robustly the high-affinity receptor for IgE, FcεRI, and thereby sense allergens. A beneficial role of vitamin D3 in AD is discussed to be important especially in patients with allergic sensitization. We hypothesized that vitamin D3 impacts FcεRI expression and addressed this in human ex vivo skin, in vitro Langerhans cells, and IDEC models generated from primary human precursor cells. We show in this article that biologically active vitamin D3 [1,25(OH)2-D3] significantly downregulated FcεRI at the protein and mRNA levels of the receptor’s α-chain, analyzed by flow cytometry and quantitative RT-PCR. We also describe the expression of a functional vitamin D receptor in IDEC. 1,25(OH)2-D3–mediated FcεRI reduction was direct and resulted in impaired activation of IDEC upon FcεRI engagement as monitored by CD83 expression. FcεRI regulation by 1,25(OH)2-D3 was independent of maturation and expression levels of microRNA-155 and PU.1 (as upstream regulatory axis of FcεRI) and transcription factors Elf-1 and YY1. However, 1,25(OH)2-D3 induced dissociation of PU.1 and YY1 from the FCER1A promotor, evaluated by chromatin immunoprecipitation. We show that vitamin D3 directly reduces FcεRI expression on dendritic cells by inhibiting transcription factor binding to its promotor and subsequently impairs IgE-mediated signaling. Thus, vitamin D3 as an individualized therapeutic supplement for those AD patients with allergic sensitization interferes with IgE-mediated inflammatory processes in AD patients.

Pollens are a major cause of seasonal allergic diseases. Weather may alter the production of pollens. Increased atmospheric temperatures lead to earlier pollination of many plants and longer duration of pollination, resulting in extended pollen seasons, with early spring or late winter. Longer pollen seasons increase duration of exposure, resulting in more sensitization, and higher pollen concentrations may lead to more severe symptoms. Climate changes in contact to pollens may affect both allergic sensitization and symptom prevalence with severity. The future consequences of climate change, however, are speculative, because the influence on humans, is complex.

Objectives. Sensitization to specific inhalant allergens is a major risk factor for the development of atopic diseases, which impose a major socioeconomic burden and significantly diminish quality of life. However, patterns of inhalant allergic sensitization have yet to be precisely described. Therefore, to enhance the understanding of aeroallergens, we performed a cluster analysis of inhalant allergic sensitization using a computational model.Methods. Skin prick data were collected from 7,504 individuals. A positive skin prick response was defined as an allergen-to-histamine wheal ratio ≥1. To identify the clustering of inhalant allergic sensitization, we performed computational analysis using the four-parameter unified-Richards model.Results. Hierarchical cluster analysis grouped inhalant allergens into three clusters based on the Davies-Bouldin index (0.528): cluster 1 (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cluster 2 (mugwort, cockroach, oak, birch, cat, and dog), and cluster 3 (Alternaria tenus, ragweed, Candida albicans, Kentucky grass, and meadow grass). Computational modeling revealed that each allergen cluster had a different trajectory over the lifespan. Cluster 1 showed a high level (>50%) of sensitization at an early age (before 19 years), followed by a sharp decrease in sensitization. Cluster 2 showed a moderate level (10%–20%) of sensitization before 29 years of age, followed by a steady decrease in sensitization. However, cluster 3 revealed a low level (

Antecedentes: en población pediátrica, pocas veces se busca la sensibilización alérgica a insectos de los órdenes Hymenoptera y Culicidae.Objetivo: establecer la prevalencia de sensibilización a abeja, mosco y hormiga roja en niños con enfermedades alérgicas.Material y método: estudio retrolectivo y descriptivo, en el que se revisaron los registros de la reactividad cutánea a alergenos de abeja, mosco y hormiga en un servicio de Alergia Pediátrica de enero de 2009 a diciembre de 2011. Se estimó la frecuencia de sensibilización y sus respectivos intervalos de confianza de 95% (IC95%).Resultados: se incluyeron 613 pacientes, 41% era del sexo femenino; la edad media del grupo fue de 6.2±3.7 años. La sensibilización alérgica al mosco fue de 15% (IC95%: 12.4 a 18.1), a abeja de 14% (IC95%: 11.4 a 16.9) y a hormiga roja de 6% (IC95%: 6.0 a 6.8); por sexo, la frecuencia no difirió significativamente. Los niños sensibles a las abejas o a las hormigas rojas tuvieron mayor edad que los no sensibilizados: 7.1 vs 6.0 años (p=0.011) y 7.4 vs 6.1 años (p=0.042), respectivamente. Durante las estaciones de otoño e invierno predominó la sensibilización a la hormiga roja.Conclusiones: hasta nuestro conocimiento, éste es el primer informe en México relacionado con la frecuencia de sensibilización a abejas, moscos y hormigas rojas realizado en niños. Además, nuestros resultados sugieren que se debe identificar de manera habitual la sensibilidad a estos insectos.

Food allergies are a major public health concern due to their widespread and rising prevalence. The increase in food allergy is partially due to Western lifestyle habits which deplete protective commensal microbiota. These microbial perturbations can result in adverse host-microbe interactions, altering the phenotype of various immune cells and instigating allergic sensitization. Although B cells are critical to allergic pathology, microbial influences on B cells have been somewhat overlooked. Here, we focus on direct and indirect interactions between bacteria and B cells and how such interactions regulate B-cell phenotype, namely antibody production (IgA, IgE, IgG1, and IgG4) and regulatory B-cell (Breg) function. Understanding how microbes modulate B-cell activity in the context of food allergies is critical to both tracing the development of disease and assessing future treatment options.

Aim: to study the sensitization profile in patients with sensitivity to Bet v1 allergen who have clinically significant respiratory symptoms of pollinosis during the birch flowering season, oral allergy syndrome (OAS), and angioedema to nuts and stone fruits. Patients and Methods: a prospective open-label study included 40 children (average age 7.52±0.64), 26 (65%) boys and 14 (35%) girls. All children had sensitization to the birch major allergen (Bet v1), symptoms of respiratory allergy during the birch flowering season, manifestations of OAS with angioedema in combination with hives or without it after eating fruits of Rosaceae family/nuts/peanuts. Children underwent general clinical and allergy researches, determination of total IgE and eosinophil cationic protein. By the method of component-resolved diagnosis of allergy (ISAC-112, ImmunoCAP), a comprehensive allergology examination for 112 allergen molecules was performed for each child. Results: the children of the study group were found to have increased values of total IgE (256.66±40.45 IU/mL) and eosinophil cationic protein (67.22±8.67 ng/mL). It was found that 57.5% of children were sensitized to tree nut storage proteins (rJug r1, rJug r2, NCoR a9, rAna o2, rBer e1), and some patients (27.5%) had increased specific IgE to non-specific lipid-transfer proteins (npLTPs) (rPru p3, NCoR a8, rAra h9, rJug r3). Antibodies to peanut storage proteins (rAra h1, rAra h2, rAra h3, rAra h6) were in 22.5% of children in the study group. Conclusion: the component-resolved diagnosis of allergy allows to determine the sensitization profile of patients. Sensitization detection to storage proteins and/or nsLTPs of nuts, peanuts and fruits is a predictor of possible severe allergic reactions. The exclusion of these products, both raw and heat-treated, reduces the number of severe acute allergic reactions in patients and prevents possible fatal outcomes. KEYWORDS: oral allergy syndrome, angioedema, children, birch, sensitization to Bet v1 allergen, storage proteins, nsLTPs. FOR CITATION: Lepeshkova T.S., Beltyukov E.K., Tsarkova S.A., Naumova V.V. Oral allergy syndrome and angioedema in patients with birch allergen sensitization: are there any high risks? Russian Medical Inquiry. 2021;5(1):21–24. DOI: 10.32364/2587-6821-2021-5-1-21-24.

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. Exposure to even minute quantities of allergens can lead to the production of IgE antibodies in atopic individuals. This is termed allergic sensitization, which occurs mainly in early childhood. Allergen-specific IgE then binds to the high (FcεRI) and low-affinity receptors (FcεRII, also called CD23) for IgE on effector cells and antigen-presenting cells. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared with IgE and do not efficiently interfere with allergen-induced inflammation. However, IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mast cells and basophils. Here, we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.

Background: Variations in Toll-like receptor 2 (TLR2) encoding gene have been associated with atopic conditions. Objective: The present work aims to analyze single nucleotide polymorphism (SNP) of TLR2 gene Arg753Gln in atopic dermatitis (AD) and its association with allergen sensitization and disease severity. Methodology: 110 AD patients and 75 healthy controls were enrolled and subjected to genotyping of TLR2 gene Arg753Gln by restriction enzyme analysis and allergy investigations. Results: TLR2 Arg753Gln SNP was significantly more frequent in the patients (48%) in comparison to the healthy group (32%) (0R= 1.7). Individuals with the G/A genotype were at a higher risk for AD development by two times. Inhalant allergens specific IgE were distinguished in 80 % of patients with TLR2 gene polymorphism. Conclusion: GA genotype of TLR2 gene is more dominant in severe cases of atopic dermatitis and associated with sensitization to certain inhalant allergens as house dust mites and pollens.