Allergen Exposure Research Articles

IgE sensitization profiles to food, inhalant and insect venom in Norwegian blood donors and their impact on blood transfusions.

Allergen-specific immunoglobulin-E (As-IgE) in blood donors (BD) can be transferred to transfusion recipients via plasma-containing blood components (PCBC) and sensitize recipient's mast cells. These cells can activate upon allergen exposure and cause allergy. This study aimed to assess sensitization profiles against an array of allergens in BD to identify donors with As-IgE and explore if this IgE can lead to allergic symptoms in recipients. Furthermore IgE sensitization was characterized in donors of PCBC that were associated with allergic transfusion reactions (ATR) in recipients. Serum samples from 300 randomly selected BD (RSBD) and 40 BD selected following 26 ATRs in patients transfused with PCBC from these donors were collected. IgE sensitization was tested by a line-blot enzyme-immunoassay and an ELISA-based IgE multiplex assay. Thirty-eight per cent of the RSBD had IgE to one or several allergens. High IgE levels with a potential to transfer to recipients of PCBC were also detected in some BD. Investigation of 2/3 of the PCBC from sensitized RSBD revealed no reports of ATR in recipients. IgE testing of donors associated with an ATR showed sensitization in 65% of the cases. We conclude that IgE testing of BD can reveal sensitization to different allergens, even though persons with severe allergies are not accepted as BD. The sensitization frequency appears higher in BD of PCBC that led to an ATR compared to the RSBD. No reports on ATR were found for PCBC from sensitized RSBD. More studies are needed to address the role of IgE-sensitization of BD in ATR.

Different Aspects of COVID-19: "Stay at Home" Increased Cat and Mite Sensitivity in Preschool Children.

Indoor allergen exposure and senitization is expected to increase significantly during the COVID-19 pandemic. The aim of this study was to assess the impact of this altered allergen exposure on allergen sensitivity patterns in children with asthma. Demographic data, clinical characteristics, and laboratory findings of asthmatic children aged 5 years and younger were assessed May 2019 to May 2020, 1 year after the start of lockdown measures. Those asthmatic children were compared with age- and sex-matched asthmatic peers assessed before the pandemic. Group I included asthmatic children who underwent skin testing within 12 months of the start of the lockdown (n = 112), while Group II included asthmatic children whose skin testing was done before the lockdown (n = 224). A total of 336 preschool children diagnosed with asthma were evaluated. House dust mite (HDM) and animal dander (cat, dog) senitization rates were significantly higher in Group I than in Group II (66.1% vs. 42.9%; OR: 2.5, 95% CI: 1.6-4.1, p < 0.001 and 8.0% vs. 1.3%; OR: 6.4, CI: 1.7-24.2, p = 0.006, respectively). However, the number of asthma attacks requiring systemic corticosteroid treatment was higher in Group I than in Group II (p = 0.001). The duration of lockdown emerged as a significant risk factor for HDM senitization (p < 0.001, OR: 2.6, 95% CI: 1.6-4.1) and animal allergen senitization (p = 0.006, OR: 6.4, 95% CI: 1.7-27.3). During the pandemic, senitization to indoor allergens, including HDM and animal dander, increased significantly in asthmatic children. This may be attributed to changes in lifestyle, increased time spent indoors and increased pet ownership.

Is gastrointestinal epithelial barrier dysfunction the only responsible for sensitization to food allergens?

Epithelial barriers are crucial defenses against pathogens and allergens, and recent theories suggest that environmental factors may compromise them, leading to type 2 inflammation and conditions such as asthma, atopic dermatitis, food allergy, and rhinitis. While skin and respiratory barriers show clear dysfunctions in allergies, the role of the gut epithelium is less defined, particularly in view of its ability to absorb nutrients and maintain immune tolerance under normal conditions. Research indicates that gastrointestinal barrier integrity typically remains preserved in food allergies, allowing for the development of immune tolerance to ingested food antigens through mechanisms like Treg cells and IgA. Allergies to cow's milk or hen's egg proteins most often resolve with age, highlighting the gut's evolving role in allergen sensitization. Studies like the LEAP (Learning Early About Peanut Allergy) trial demonstrate the preventive benefits of early allergen exposure against peanut allergy, supporting the dual allergen exposure hypothesis. New allergens such as alpha-Gal and gibberellin-regulated proteins (GRP) reveal distinct sensitization pathways beyond traditional ingestion routes, implicating non-dietary sources in allergen introduction. Altogether, there is lack of evidence suggesting that the intestinal epithelium is disrupted in food allergy.

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma

BackgroundAirway tissue eosinophilia can be an observed feature of obesity associated T2 asthma, but the processes mediating this inflammation are unknown. ObjectiveWe investigated a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma. MethodsWe assessed associations between body mass index and airway eosinophilia, leptin and eotaxin production in 78 asthma participants, 36 of which exhibited obesity. Cultured human airway fibroblasts and mouse models of chronic allergic airway disease were used to evaluate leptin’s effect on eotaxin production and lung eosinophilia. The role of interleukin-13 receptor alpha 2 (IL-13Rα2) in mediating these processes was examined using specific neutralizing antibodies in vitro. ResultsIn T2 asthma participants with obesity, we observed that airway tissue eosinophilia did not associate with traditional T2 inflammation metrics such as peripheral and/or bronchoalveolar lavage fluid (BALF) eosinophil counts or with fractional concentration of exhaled nitric oxide (FeNO). Alternatively, we observed elevated BALF leptin and eotaxin-1 levels. In airway fibroblasts from asthma participants, leptin augmented IL-13-induced eotaxin-1 and -3 production and IL13RA2 expression. In mice, elevated leptin promoted airway IL-13Rα2 and eotaxin production by lung fibroblasts and lung tissue eosinophilia following chronic house dust mite allergen exposure. Inhibition of IL-13Rα2 reduced combined leptin and IL-13-stimulated eotaxin secretion by human airway fibroblasts. ConclusionWe identified a potential association explaining airway tissue eosinophil retention in obesity-associated T2 asthma through leptin-mediated enhancement of IL-13-induced eosinophil chemokine production by airway fibroblasts, a process requiring IL-13Rα2.

Minimizing Indoor Allergen Exposure: What Works?

Allergic rhinitis and asthma morbidity has been linked to indoor allergen exposure. Common indoor allergens include dust mites, cats, dogs, rodents, and cockroaches. These allergens are ubiquitous and often difficult to remove from the home, making long-lasting reduction strategies difficult to achieve. Identifying strategies for reducing the presence of indoor allergens in homes could be utilized to decrease allergic disease burden, improve symptomology, reduce healthcare costs, and improve patients' quality of life. Studies have yielded mixed results with regard to specific environmental control measures in reducing indoor allergen levels and in improving clinical outcomes of allergic disease. In this review, we assess the available evidence of the effectiveness of environmental control measures in reducing indoor allergens and the potential clinical impact of these measures.

Low-dose IL-2 in birch pollen allergy: A phase-2 randomized double-blind placebo-controlled trial

Regulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2LD) activates Treg cells. Our aim was to assess IL-2LD efficacy for controlling clinical responses to allergen exposures. RHINIL-2 was a phase-2a, randomized, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included; 66% of them had concomitant asthma. All had a total nasal symptom score (TNSS) of 5 or more following nasal exposure to BP in an environmental exposure chamber. Patients received 1 MUI per day of IL-2 (n= 12) or placebo (n= 12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the environmental exposure chamber were evaluated by using TNSS, the rhinitis visual analog scale (VAS), and spirometry. The primary efficacy end point was the difference in TNSS area under the curve (AUC) between inclusion and day 40. IL-2LD treatment induced a significant expansion of Treg cells. The difference in TNSS AUC between inclusion and day 40 AUC in the IL-2 and placebo groups was not significant. TNSS and visual analog scale AUCs were significantly reduced from baseline to day 40 in the IL-2LD group only (P= .04 and P= .01, respectively). The ratio of FEV1 to forced vital capacity (FEV1P) and the forced midexpiratory flow (FEF25%-75%) showed improvement in the IL-2LD-treated versus in the groups given placebo at day 40 (P= .04 and P= .04, respectively). However, the short treatment duration used in this study could not have effects on specific IgE or IgG4 levels given their half-life. There were no severe treatment-related adverse events. IL-2LD is well tolerated in patients with allergy, even in those with asthma, thus clearing the path for further therapeutic development. Our work suggests that Treg cells can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.

Addressing health disparities in food allergy: A Position Statement of the AAAAI Prior Authorization Task Force

Self-reported food allergies (FAs) affect approximately 8% of the US pediatric and approximately 10% of the adult population, which reflects potentially disproportionate increases among ethnically and racially minoritized groups. Multiple gaps and unmet needs exist regarding FA disparities. There is reported evidence of disparities in FA outcomes, and the FA burden may also be disproportionate in low-income families. Low family income has been associated with higher emergency care spending and insecure access to allergen-free food. Pharmacoinequity arises in part as a result of structural racism still experienced by historically marginalized populations today. Historically redlined communities continue to experience greater rates of neighborhood-level air pollution and indoor allergen exposure, lack of transportation to medical appointments, poverty, and lower prescription rates of necessary medications. Clinical research needs racially and ethnically diverse participation to ensure generalizability of research findings and equitable access to medical advances, but race reporting in clinical trials has been historically poor. Addressing health disparities in FA is a priority of clinical care, with professional organizations such as the American Academy of Allergy, Asthma & Immunology having a prominent role to play in mitigating the challenges faced by these individuals. In this position statement we recommend some key steps to address this important issue.

AI-Enhanced Allergy Diagnostics: Streamlining Healthcare and Reducing Costs

Abstract Issue/Problem WHO projects a shortfall of 10 million health workers by 2030. One area particularly lacking technological support is allergy diagnostics. The World Allergy Organization recognizes skin tests as the gold standard for allergy diagnostics, yet these tests are still manually assessed. General practitioners lack the time and tools, leading them to focus on treating the symptoms without addressing the causes. Description of the problem Symptomatic treatment of allergy can lead to the development of asthma in 30-40% of patients, increasing healthcare costs and causing lost productivity. The shortage of allergists further exacerbates this issue in many countries. Results Research conducted by the Military Institute of Medicine in Warsaw, in collaboration with a company producing automated allergy testing systems, explored a solution for allergy diagnostics, analyzing the entire process from the patient’s initial visit to desensitization therapy. The solution uses AI algorithms to reusable existing patient data and analyze patient history, correlate symptoms, medications, and allergen exposure, streamlining diagnostics and treatment. Patients at high risk undergo a computer-assisted interview to determine allergen panels. The only manual step is applying allergens to the skin, after which AI performs the reading and diagnosis. Clinical trials involving around 300 patients demonstrated high sensitivity and specificity, along with significant time savings for allergists and other medical staff, averaging 40 minutes per patient. The HTA evidence base will be ready by the end of this year. Lessons The integration of this AI-supported diagnostic method can eliminate bottlenecks in allergy diagnostics, improving health outcomes and reducing healthcare costs. However, its effectiveness depends on having at least few years of patient treatment data available. Without access to patient data, the method can be used in part to objectify PRICK test readings. Key messages • AI-supported diagnostics streamline allergy testing, reducing time and costs in the healthcare system. • The most accurate technique currently available for the automated reading of test results is that which evaluates the response to an allergen in the dermis in two spectra.

Aging, brain-derived neurotrophic factor, and allergen-induced pulmonary responses in mice.

Asthma in the elderly is being recognized as more severe, resistant to standard therapies, and having greater morbidity. Therefore, it comes important to understand the impact of aging-associated airway structure and function changes towards pathogenesis of asthma in the elderly. Here, airway smooth muscle plays important roles in airway hyperreactivity and structural remodeling. The role of smooth muscle in asthma can be modulated by growth factors (including neurotrophins such as brain-derived neurotrophic factor (BDNF)) and pro-inflammatory senescence factors. In this study, we investigated aging effects on airway hyperreactivity, structural remodeling, inflammation, and senescence in a mouse model of allergic asthma. C57BL/6J wildtype mice or smooth muscle-specific BDNF knockout mice at 4, 18 and 24 months of age were intranasally exposed to mixed allergens (ovalbumin, aspergillus, Alternaria, and house dust mite) over 4 weeks. Assessing lung function by FlexiVent, we found that compared with 4 month old mice, 18 and 24 month old C57BL/6J mice showed decreased airway resistance and increased airway compliance after PBS or MA treatment. Deletion of smooth muscle BDNF blunted airway hyperreactivity in aged mice. Lung histology analysis revealed that aging increased bronchial airway thickness and decreased lung inflammation. Multiplex assays showed that aging largely reduced allergen-induced lung expression of proinflammatory chemokines and cytokines. By immunohistochemistry staining, we found that aging increased bronchial airway expression of senescence markers, including p21, phospho-p53 and phospho-gH2A.X. Our data suggest that aging associated increase of airway senescence in the context of allergen exposure may contribute to asthma pathology in the elderly.

Gut microbiome impact on childhood allergic rhinitis and house dust mite IgE responses.

The correlation between the gut microbiota and airway inflammation in childhood allergic rhinitis (AR), particularly concerning allergen exposure, remains insufficiently explored. This study aimed to link gut microbiota changes with house dust mite (HDM)-specific IgE responses in pediatric AR. Using metagenomic shotgun sequencing, we compared the fecal microbiota of 60 children with HDM-AR to 48 healthy controls (HC), analyzing the link to IgE reactions. We examined the effects of oral Escherichia (E.) fergusonii treatment in mice sensitized with ovalbumin and HDM on allergic symptoms, mucosal cell infiltration, Th1/Th2/Tregs balance in the spleen, serum cytokine levels, and E. fergusonii presence in feces. Children with HDM-AR have a less diverse gut microbiome and lower levels of E. fergusonii compared to controls, with a negative correlation between E. fergusonii abundance and HDM-specific IgE levels. In mice sensitized with OVA and HDM, oral administration of E. fergusonii improved allergic symptoms, reduced nasal eosinophils/mast cells infiltration and adjusted Th cell populations towards a non-allergic profile in splenic lymphocytes with exception of IFN-γ change in serum. These findings underline the potential of targeting gut microbiota, particularly E. fergusonii, in managing childhood HDM-AR, suggesting a promising approach for future interventions. The composition and distribution of gut microbiota in children with HDM-AR are significant changed. The abundance of Escherichia genus is decreased in HDM-AR children. HDM-specific IgE levels are strongly negatively associated with E. fergusonii abundance. Oral administration of E. fergusonii effectively suppresses allergic responses in murine model. These findings offer novel insights into the diagnosis and treatment of HDM-AR, which suggested that E. fergusonii holds promise as a potential therapeutic avenue for managing HDM-AR.

Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.

In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.

Oral immunotherapy improves the quality of life of adults with food allergy

BackgroundOral immunotherapy (OIT) has become the standard of care for children with food allergy (FA) and has substantially improved their quality of life. The effect of OIT on the quality of life in adults, however, has been studied to a much lesser degree.MethodsPatients with food allergy aged ≥ 18 years who underwent OIT at Shamir Medical Center completed the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) before and at the end of treatment. Adults with FA not undergoing OIT who completed the FAQLQ-AF at 2 time points, served as controls.ResultsA total of 44 adults, median age 23.4 years, who underwent OIT for milk (n = 19), egg (n = 2), peanut (n = 9), sesame (n = 6), and tree nuts (n = 8), and 11 controls were studied. The median OIT starting dose was 23.8 mg protein. 33 patients (75%) reached full desensitization within a median of 10.3 months. The FAQLQ-AF baseline scores were comparable between the study and control groups for all items except for Food Allergy related Health (FAH) item in which the study group had a significantly better score (p = 0.02). At the second time point, the study group had significantly better scores in all items (Allergen Avoidance and Dietary Restrictions (AADR), p = 0.02; and Emotional Impact (EI), Risk of Allergen Exposure (RAE), FAH and the Total Score, p < 0.01). The change in scores for the study group was significantly better, statistically and clinically, in AADR, p = 0.04; EI, p < 0.01; RAE, p = 0.01, and in the total score, p = 0.01.ConclusionsOIT significantly improves quality of life of adults with FA. This finding adds important support for providing OIT in this population.

Investigation into the Effects of Allergen Exposure and Topical Vinegar and Water Spray on Skin Barrier Parameters in Atopic Dogs.

Increased skin pH and transepidermal water loss (TEWL) are documented in atopic people and dogs but no study has investigated how these parameters change during an allergy flare. Our primary aim was to challenge atopic beagles to dust mites and measure pH and TEWL during a flare of atopic dermatitis and correlate these parameters to clinical signs. A secondary aim was to evaluate in a randomized placebo-controlled study whether the daily application of 50/50 vinegar spray improves clinical signs and affects skin parameters despite the allergen challenge. Fifteen atopic dogs were challenged epicutaneously twice weekly for 2 weeks with allergen application on the inguinal and medial thigh areas. The severity of dermatitis was scored daily (CADESI-03). TEWL and pH were measured daily on the inguinal and medial thigh areas. A repeated measures ANOVA showed the significant effect of time, with increased pH (p < 0.0001), TEWL (p < 0.0001), and CADESI (p < 0.0001) during allergen challenge. Significant positive correlations were found between CADESI and pH (r = 0.3556; p < 0.0001), CADESI and TEWL (r = 0.36; p < 0.0001), and pH and TEWL (r = 0.45; p < 0.0001). Daily application of 50/50 vinegar did not improve dermatitis, pH, and TEWL compared to the control treatment. It can be concluded that both pH and TEWL are markers of disease severity in canine atopic dermatitis.

Potential association between allergenic food exposure and skin disease in Bangladesh: An application of principal component logistic regression (PCLR).

Allergenic foods can trigger skin conditions, yet their impact in Bangladesh remains underexplored. This study aims to investigate the potential association between exposure to allergenic foods and the development of skin disease across Bangladesh. We conducted a cross-sectional survey with 970 respondents from the divisions of Dhaka, Sylhet, Rangpur, and Chattogram who self-reported skin disease triggered by food allergens. We analyzed the data using multiple response analysis and principal component logistic regression. Approximately 64% of respondents had skin disease attributable to allergenic foods, with a relatively higher proportion among females (52%) than males (48%). Beef (67%), Brinjal (47.1%), Hilsa (45.8%), and Shrimp (23.7%) were the most frequently cited allergenic foods. Principal component logistic regression identified two highly significant principal components: the first representing Hilsa, Beef, and Brinjal (odds ratio = 2.256), and the sixth reflecting Corn (odds ratio = 1.342). Individuals who consumed foods with high loadings of the first principal component were 125.6% more likely to develop skin disease than nonconsumers, while those exposed to Corn had a 34.2% higher risk. The findings highlight prevalent allergenic foods in Bangladesh and their substantial impact on skin health, underscoring the need for dietary awareness and tailored interventions to mitigate allergic skin conditions in this population.

Epicutaneous immunotherapy for the treatment of peanut allergy.

Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late-stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild-to-moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long-term efficacy and tolerability.

Ayurveda Management of Allergic Rhinitis: Protocol for a Randomized Controlled Trial.

Allergic rhinitis (AR) is the inflammation of the membranes lining the nose due to allergen exposure and is characterized by sneezing, nasal congestion, itching of the nose, or postnasal discharge. The prevalence varies worldwide, perhaps due to the geographic and aeroallergen differences, with 10% to 30% of the world's population experiencing AR. In this study, Anu Taila Nasya, Naradiya Laxmivilas Rasa, and Shirishadi Kwath will be compared to a fluticasone nasal spray. The primary aim is to assess the efficacy of Ayurvedic management for AR (or vataja pratishyaya) by comparing it to a conventional control group. The secondary aims are to determine the mean change in the nasal endoscopy index and the mean change in the laboratory tests. This ongoing study is an open-label randomized controlled interventional trial, with a sample size of 90 both in the trial and standard control group (including dropouts, 20%), and will be carried out for 24 months. Participants in the trial group will receive Ayurvedic treatment, that is, Anu Taila Nasya (6 drops in each nostril for 7 days for 3 consecutive weeks), Naradiya Laxmivilas Rasa (250 mg twice per day), and Shirishadi Kwath (40 ml twice per day for 45 days). The participants in the control group will receive a fluticasone propionate nasal spray (2 sprays once per day for 45 days). The primary outcome will include the mean change in the Control of Allergic Rhinitis and Asthma Test score, and the secondary outcomes will include the mean change in the nasal endoscopy index (assessment of nasal membrane color, pale or hyperemia; rhinorrhea, watery or yellow; and inferior turbinate swelling, hypertrophy) and the mean change in the laboratory tests. As of May 2024, 72 patients have been enrolled in both groups. Data analysis should be completed by February 2025. The study will be reported following standard guidelines for reporting randomized controlled trials. Clinical results will be disseminated through conferences and peer-reviewed publication in a relevant journal. The Ayurvedic approach could be an evidence-based therapeutic tactic for the management of AR. Clinical Trials Registry India CTRI/2023/06/053395; https://tinyurl.com/564d2zz8. DERR1-10.2196/56063.

Effects of glial-derived neurotrophic factor on remodeling and mitochondrial function in human airway smooth muscle cells.

Airway smooth muscle (ASM) cells play important roles in airway remodeling of asthma. Our previous studies show that in vivo administration of glial-derived neurotrophic factor (GDNF) in mice induces thickening and collagen deposition in bronchial airways, whereas chelation of GDNF by GFRα1-Fc attenuates airway remodeling in the context of allergen exposure. To determine whether GDNF has direct effects on ASM, in this study, we examined GDNF in ASM cells from normal versus asthmatic humans. We found that GDNF treatment of human ASM cells had only minor effects on cell proliferation and migration, intracellular expression or extracellular deposition of collagen I (COL1), collagen III (COL3), and fibronectin. Endoplasmic reticulum (ER) stress response and mitochondrial function have been implicated in asthma. We investigated whether GDNF regulates these aspects in human ASM. We found that GDNF treatment did not affect ER stress protein expression in normal or asthmatic cells. However, GDNF treatment impaired mitochondrial morphology in ASM but without significant effects on mitochondrial respiration. Thus, it is likely that in vivo effects of GDNF on airway remodeling per se involve cell types other than those on ASM, and thus ASM may serve more as a source of GDNF rather than a target.NEW & NOTEWORTHY Our previous study suggests that glial-derived neurotrophic factor (GDNF) is involved in allergen-induced airway hyperreactivity and remodeling in vivo. Here, we show that GDNF has no direct effects in remodeling of human airway smooth muscle (ASM) but GDNF dysregulates mitochondrial morphology in human ASM in the context of asthma.

Skin cancer diagnosis associated with asthma and hay fever: a nationwide cross-sectional study.

Asthma is a respiratory disorder caused by airway inflammation which may worsen after allergen exposure. Recent cohort studies demonstrate a positive association between skin cancer and asthma or hay fever (allergy to outdoor allergens such as pollen). Nationally-representative data for adults in the United States remains limited. We aimed to characterize skin cancer prevalence among individuals in the United States who have asthma or hay fever. To achieve this aim, we extracted nationwide cross-sectional data from 16,277 adult participants (total survey-weighted sample = 174,765,931) of the Third National Health and Nutrition Examination Survey from 1988 to 1994. This study uses survey-weighted regression to compare the nationwide prevalence of skin cancer among participants with or without a history of asthma or hay fever. Sensitivity analysis examined the influence of sex, 25-hydroxyvitamin D, chronic bronchitis or emphysema, geographical region, urban proximity, and oral glucocorticoid use. Of the included participants, the age-adjusted prevalence of skin cancer was 7.2%, similar to national estimates. Skin cancer prevalence was higher among participants who had asthma with hay fever (adjusted prevalence ratio, 1.79; 95% confidence interval, 1.16, 2.76), but not among participants with asthma only or hay fever only. Similarly, skin cancer prevalence was higher for those with asthma and positive pollen allergen skin prick testing (SPT), but not for those with hay fever and positive pollen SPT. No association was noted between skin cancer and wheezing triggered by pollen. Hay fever or immunoglobulin-E sensitization to pollen may increase skin cancer prevalence among individuals with a history of asthma.

Identification of a New and Effective Marker Combination for a Standardized and Automated Bin-Based Basophil Activation Test (BAT) Analysis.

(1) Background: The basophil activation test (BAT) is a functional whole blood-based ex vivo assay to quantify basophil activation after allergen exposure by flow cytometry. One of the most important prerequisites for the use of the BAT in the routine clinical diagnosis of allergies is a reliable, standardized and reproducible data analysis workflow. (2) Methods: We re-analyzed a public mass cytometry dataset from peanut (PN) allergic patients (n = 6) and healthy controls (n = 3) with our binning approach "pattern recognition of immune cells" (PRI). Our approach enabled a comprehensive analysis of the dataset, evaluating 30 markers to achieve optimal basophil identification and activation through multi-parametric analysis and visualization. (3) Results: We found FcεRIα/CD32 (FcγRII) as a new marker couple to identify basophils and kept CD63 as an activation marker to establish a modified BAT in combination with our PRI analysis approach. Based on this, we developed an algorithm for automated raw data processing, which enables direct data analysis and the intuitive visualization of the test results including controls and allergen stimulations. Furthermore, we discovered that the expression pattern of CD32 correlated with FcεRIα, anticorrelated with CD63 and was detectable in both the re-analyzed public dataset and our own flow cytometric results. (4) Conclusions: Our improved BAT, combined with our PRI procedure (bin-BAT), provides a reliable test with a fully reproducible analysis. The advanced bin-BAT enabled the development of an automated workflow with an intuitive visualization to discriminate allergic patients from non-allergic individuals.

The potential of orally exposed risk factors and constituents aggravating food allergy: Possible mechanism and target cells.

Food allergy is a significant concern for the health of humans worldwide. In addition to dietary exposure of food allergens, genetic and environmental factors also play an important role in the development of food allergy. However, only the tip of the iceberg of risk factors in food allergy has been identified. The importance of food allergy caused by orally exposed risk factors and constituents, including veterinary drugs, pesticides, processed foods/derivatives, nanoparticles, microplastics, pathogens, toxins, food additives, dietary intake of salt/sugar/total fat, vitamin D, and therapeutic drugs, are highlighted and discussed in this review. Moreover, the epithelial barrier hypothesis, which is closely associated with the occurrence of food allergy, is also introduced. Additionally, several orally exposed risk factors and constituents that have been reported to disrupt the epithelial barrier are elucidated. Finally, the possible mechanisms and key immune cells of orally exposed risk factors and constituents in aggravating food allergy are overviewed. Further work should be conducted to define the specific mechanism by which these risk factors and constituents are driving food allergy, which will be of central importance to the targeted therapy of food allergy.