Allergies

In vitro tests of cellular activity form part of the diagnostic algorithm of drug hypersensitivity reactions. Because of the wide range of pharmacological mechanisms, clinical symptoms, genetic components, and laboratory tests involved, it is important to know how a particular test performs in the diagnostic procedure. We carried out a detailed retrospective analysis of more than 6000 measurements of numerous drug compounds tested in 738 serum samples over the past 6 years. Our cell viability-based lymphocyte transformation had a coefficient of variation of 10% and showed similar performance over the whole range of tested ages. With an adequate number of parallel measurements, the test can identify modest increases in stimulation indices with high confidence. Similar percentages of analytically positive responses (11.4%, 13.5%, and 9.7%) were observed for the three most frequently tested drug groups, namely, antibiotics, non-steroid anti-inflammatory agents, and anesthetics. These results confirm that cell viability tests are suitable alternatives for proliferation assays in drug allergy testing. Full article

Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD. Full article

This review explores strategies for mitigating food allergies by treating foods with biopolymers, bioactive compounds, and food-grade enzymes. Biopolymers like chitosan, alginate, and pectin show potential in reducing the allergenic properties of food. Polyphenols such as quercetin, resveratrol, curcumin, and epigallocatechin gallate demonstrate promise as anti-inflammatory molecules that can lessen the symptoms and severity of allergic reactions. Enzymes, including proteases such as pepsin, papain, and bromelain, and transferases like transglutaminase, offer the potential to reduce the allergenic potency of proteins by various mechanisms, though more research is needed for the optimization and assessment of the safety and palatability of treated foods. Overall, this review offers insights into potential strategies to alleviate allergic reactions by reducing the allergenic properties of food proteins. Full article

Introduction: Lipid Transfer Proteins (LTPs) are plant-derived panallergens that have emerged as significant allergens in Mediterranean populations. Though less common in children, LTP allergies represent a critical consideration for physicians diagnosing plant food allergies in this demographic. Methodology: PRISMA-ScR guidelines were followed. A search with specific terms was performed in searchable databases. Two of the authors extracted and evaluated the data. Results: A total of 21 original studies and 6 case reports focusing on LTP allergies in the paediatric population met the inclusion criteria. Diagnostic tools, predictive markers and management options for LTP allergies were examined. Allergens, clinical presentation and history were the diagnostic tools investigated. The clinical and laboratory phenotypes of the patient were considered possible predictive markers for the evaluation and progression of LTP allergies. Lastly, dietary modifications and sublingual immunotherapy were identified as the main focus of LTP allergy management. Discussion: A summary of the results is presented, and at the same time, questions concerning the nature of LTP allergies and their management are raised. Conclusions: LTP allergy in children is something physicians should be aware of. Further research is needed to establish the differences in LTP allergies in children and adults and the effectiveness of immunotherapy in paediatric populations. Full article

Food allergies (FAs) represent a significant and growing global health issue, with increasing prevalence across different age groups. This review provides a comprehensive analysis of the epidemiology, mechanisms, and risk factors involved in FA development. Currently, FAs are estimated to affect 2% of the general population, with higher rates in children (~8%). However, these figures may be inaccurate because of the reliance on self-reported data and immunoglobulin E (IgE) testing, which may not reflect clinically confirmed cases. Environmental and genetic factors, including exposure to bacterial toxins, dietary habits, and the gut microbiota, play critical roles in FA development. Specifically, Staphylococcus aureus enterotoxins are implicated in disrupting intestinal barriers and enhancing immune sensitization to allergenic proteins. This immune dysregulation promotes Th2 responses and compromises regulatory T cell function, crucial elements in allergy pathogenesis. As the prevalence of FAs continues to rise, there is a pressing need for accurate diagnostic tools, heightened public awareness, and effective prevention strategies. Further research is needed to elucidate the specific role of bacterial toxins and other environmental factors in FA development to advance clinical management approaches. Full article

Background/Objectives: This study assessed teacher comfort in supporting the medical management of children with asthma in elementary and middle schools in two southern states in the U.S. Teacher comfort in asthma management is a largely underexplored area yet holds promise to support medical management in schools. Methods: Using survey methods, data were gathered from a random sample of teachers in two southern U.S. states (n = 574). Data from the Teacher Capability and School Resource Scale for Asthma Management scale were used to assess teacher comfort and capability in managing stressful asthma management episodes. Results: Teachers expressed comfort in supporting children with asthma in their classrooms. On the Teacher Capability in Social and Emotional Aspects of Asthma Management (SEAM) factor, the mean rating was 3.89 (SD = 0.83) out of 5, and the mean rating for the School Resources/Institutional Capability for Asthma Management factor was 3.77 (SD = 0.99) out of 5. Conclusions: The findings demonstrate that access to school, community, and medical resources; coordinated school-based asthma care plans; and pre-service preparation improve teacher comfort. School nursing support is needed for teacher education. Full article

Since the publication of the Adverse Childhood Experiences (ACEs) Study in 1998, there has been a dramatic increase in the number of studies exploring the immunoendocrinological sequelae of toxic stress. However, the literature exploring this in relation to paediatric atopy predominantly revolves around asthma. This review aims to (1) explore the association between ACEs and non-asthmatic, non-iatrogenic paediatric allergies (NANIPA) in the developed world and (2) further focus on the association between exposure to violence and NANIPA. Methods: PubMed and Scopus were searched for articles examining adversity and NANIPA before age 18. Non-English papers, publications before 1998, reviews, opinion pieces and case reports/series were excluded. Screening, data extraction, and risk-of-bias were independently reviewed by the first two authors. Results: Nine of the one thousand eighty-nine records identified were included. Four pertained to objective 1, four to objective 2, and one pertained to both. Regarding objective 1, all studies reported a positive dose-response relationship between ACEs and NANIPA, which was most significant among preschoolers and diminished with age. Studies relevant to objective 2 were too heterogenous to compare. However, two interesting associations emerged: (1) The types of violence significantly associated with NANIPA in adolescence differ in a sex-dependent manner, and (2) verbal abuse and bullying are the violence types most powerfully and significantly associated with NANIPA. Conclusion: Psychological stress is a probable IgE-independent driver of atopy in children exposed to adversity and/or violence. While the literature is too underdeveloped to allow for meaningful cross-comparison between studies, this review has identified many interesting areas for future research. Full article

Allergic Rhinitis (AR) currently affects 27% of young adults (18–24 years old) in Australia. Although the nature of AR and its management are well-researched in adult and paediatric populations, little is known about young adults. Given the biopsychosocial developmental challenges faced by young adults, this study aims to investigate young adults’ AR management and the source of its influence. A total of 185 young adults with AR in Australia completed an online survey. Seventy-eight percent were female and had a mean age of 21.9 years old. The majority (99%) had moderate to severe symptoms and affected at least one aspect of their quality of life (97%). Despite this, only 11% of participants were using appropriate medications. Parents (50%) were the most common influencer in young adults’ medication use, and general practitioners were most commonly sought for information (63%) and advice (70%). Young adults do not manage their AR with appropriate medications despite consulting healthcare providers, and this was reflected in the heavy burden reported on their quality of life. This study bridges our gap in understanding and shows that young adults lack developmentally appropriate support to equip them with the health literacy skills required to transition into adult healthcare. Full article

Although the small airway component of chronic asthma is becoming a more important topic, its impact in the daily assessment of pediatric asthma is limited. The intrinsic airway autonomic control in asthma suggests some potential mechanisms by which more distal obstruction may dominate in some situations. We suggest theoretical possibilities for small airway dominance and present clinical data supporting this possibility. Full article

This study was conducted using data from the SCAALA (Social Change Asthma and Allergy in Latin America) cohort in Brazil from 2005 to 2013. We examined the seroprevalence and risk factors of toxocariasis, a parasitic infection leading to conditions such as visceral larva migrans, utilizing an indirect ELISA with T. canis antigens, alongside with data from questionnaires, eosinophil counts, sIgE to aeroallergens, IL-10 levels, and Skin Prick Test results; the research provided insights into the disease’s dynamics. The prevalence of anti-Toxocara spp. IgG increased from 48% to 53% over the studied period, with a 25% increase in new cases in 2013. The significant risk factors included age and pet exposure, while higher maternal education and living on paved streets were found to offer protection. The study uncovered a complex interaction between Toxocara spp. infection and the immune system, indicating that the infection could both trigger inflammation and modulate skin reactions. Based on these findings, the study proposed a roadmap for controlling toxocariasis, which includes strategies such as enhancing public education about the disease and preventive measures, improving environmental sanitation, strengthening veterinary control measures like pet deworming, increasing access to healthcare and screening, and implementing community-based interventions to address the identified risk factors. These measures aim to reduce the prevalence of toxocariasis and its impact on public health by addressing environmental and socioeconomic risk factors, providing a pathway to significantly reduce the burden of this parasitic infection. Full article

Food allergy, particularly peanut allergy (PA), is a growing health concern affecting millions globally. PA can lead to severe reactions, including fatal anaphylaxis. Despite the availability of FDA-approved therapies like Palforzia, a cure remains elusive. Current immunotherapies show promise but lack a definitive cure. This study applies an established computational biology tool to design aptamers targeting Ara h1 and Ara h2. The in silico design aims to streamline the selection process, enabling cost-effective and rapid identification of aptamer candidates. The developed aptamers (AYA22A, including AYA22AR321, AYA22AR211, and AYA22AR524), demonstrated efficacy in inhibiting degranulation of RBL-2H3 cells (rat basophilic leukemia cell line) in vitro. They showed promise in neutralizing peanut allergen-induced immune responses. The selected aptamers inhibited degranulation in RBL-2H3 cells, addressing concerns in raw peanuts. Moreover, these aptamers demonstrated stability and effectiveness in peanut plant seeds and commercial products. Our aptamers exhibited potential in modulating immune responses associated with peanut allergy. They influenced Th1/Th2 balance, indicating a role in cytokine regulation. In vitro studies also showed the aptamers’ impact on immune cell expression and cytokine production, resembling responses observed with established immunotherapies. The findings suggest AYA22A aptamers as a potential therapeutic option for peanut allergy, providing a basis for further in vivo investigations. Full article

Background: Despite the importance of caregivers being trained in anaphylaxis management and the use of adrenaline auto-injectors (AAIs), studies have revealed inadequate caregiver knowledge. The caregiver anaphylaxis knowledge in an Irish population has not been previously assessed. This study aims to evaluate the anaphylaxis management knowledge and AAI administration proficiency among parents of children with food allergies. Methods: The parents of children with food allergies who were prescribed an AAI were invited to take part in a study involving online education. The participants completed an online questionnaire assessing anaphylaxis knowledge. They then took part in an online educational intervention where their AAI administration ability was assessed. Results: Out of a total score of 12, the mean anaphylaxis knowledge score was 9.76/12, SD 1.577, or 81.33%. Of the 152 participants, 26.7% (n = 40) performed all three critical AAI administration steps correctly. A household income under EUR 40,000 per annum reduced the likelihood of successful AAI administration (OR 0.33 95% CI 0.125–0.87, p = 0.025). Regarding the AAI devices, 46.4% claimed to have switched between devices at least once before. Conclusions: The parents demonstrated good knowledge of anaphylaxis management, but the prevalence of device switching underscores the importance of comprehensive AAI training. Future assessments should include evaluations of enhancements in knowledge, anxiety levels, and overall quality of life. Full article

Updated notions about the so-called hygiene hypothesis consider now that helminths may have influence in the training of the immune system during childhood. Considering the similar type of immune response between helminth infections and allergic illnesses, the objective of this study was to evaluate how structural and functional conservation between house-dust mite allergens and their helminth orthologs might contribute to the cross-induction of IgE responses in allergies and helminthiasis. Amino acid sequences from group-1, -2, -5, -9, -10, -18, -21, and -23 allergens of the house dust mite Dermatophagoides pteronyssinus were retrieved from curated databases, and orthologs were identified in other mite species and different helminth parasites. We also assessed structural, conservational, functional, and immunologic relationships between these major mite allergens and their helminth counterparts. De novo 3D-modelling, B-cell epitopes prediction, structural conservation, and docking analyses were analyzed by Robetta platform, ElliPro and CBTope, RaptorX, and Z-Dock, respectively. Our results extend previous findings on structural conservations between major allergens and parasite proteins and show that these conservations go beyond the well-known conservations and may account for the observed immunological cross-reactions. This understanding can contribute in the near future to the development of more specific serological testing for mite-induced allergies and helminthiasis. Full article

According to parental reports, about 10% of children are believed to be allergic to at least one antibiotic, leading to the prescription of second line medications. This incurs higher costs, results in less effective treatments, and contributes to global concern of antibiotic resistance. De-labeling programs could mitigate these problems. The primary objectives of this study were to assess the proportion of children that tolerate the suspected antibiotic well through allergy testing and, secondly, to examine which information in their medical history correlates with a positive test result. Children with a history of antibiotic allergy were categorized into high- and low-risk groups for immediate allergic reaction. The latter underwent oral provocation testing (OPT), while the high-risk group underwent the test only after negative skin tests (STs). In total, 76.8% of children tolerated the tested antibiotic well. Among children with positive OPT, two (8.0%) had to receive adrenaline for symptom resolution. Children who had exhibited suspected symptoms within one hour after antibiotic administration, and those with a history of asthma or food allergy, had an increased risk of positive allergic testing (p < 0.05). In conclusion, the adoption of a standardized protocol for an antibiotic allergy de-labeling program is essential for every allergy department. Full article

Background: Food allergy management requires avoidance of allergenic food. While the direct costs of food allergy management have been described, avoidance may also contribute to time and opportunity costs. We aimed to conduct a scoping review of the peer-reviewed literature on the indirect costs of food allergy, and to characterise these costs through a series of fictitious case studies. Methods: We performed a scoping review, guided by Arskey and O’Malley’s methodological framework, and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews. Eligible studies included original, peer-reviewed, English language literature with no lower limits to publication dates, which addressed the indirect costs of food allergy, including time and opportunity costs. A search strategy was developed by content experts with experience performing multi-database scoping reviews. The search was performed on 10 July 2023, managed using Rayyan (Cambridge, USA), and screened for eligibility. Results: Searches yielded 104 articles. After deduplication, 96 articles were screened at the title and abstract level; 12 articles were included following full-text screening. Of these, three studies were performed on adults with food allergy, eight studies were based on data collected from caregivers of children with food allergy, and one study made use of data reflecting adults and caregivers of children with food allergy. Collectively, indirect costs were identified as higher amongst those with vs. without food allergy. The few studies on age and food allergy differences (e.g., type and number of food allergies, history of reaction) are equivocal. Conclusions: The limited body of peer-reviewed literature supports that food allergy commonly carries substantial indirect costs across diverse measurement tools, albeit with age-group differences. Full article

Documented penicillin allergies are associated with an increased risk of surgical site infections (SSIs), and first-line antibiotics (e.g., cefazolin) are associated with a lower risk of SSIs. The goal of this study was to evaluate the effect of a pharmacist-driven penicillin allergy de-labeling pilot program on the use of preoperative cefazolin in selected surgery patients with documented penicillin allergies. This single-center, quasi-experimental study included adult patients with a charted penicillin allergy who underwent CT or spine surgery in 2021 (control group) or during the 6-month intervention pilot (October 2022–March 2023). In the intervention group, qualifying patients were interviewed via phone to assess allergy history. Qualified patients were de-labeled or referred to an allergist for outpatient skin testing and/or oral challenge. The primary outcome was the rate of cefazolin use preoperatively. Secondary outcomes included 30-day SSIs, Clostridioides difficile infection, acute kidney injury, readmission, and hospital length of stay. Of the intervention group, 57 (79.2%) patients completed the interview. Cefazolin was used preoperatively in 71.0% (152) of the control group versus 88.9% (64) of the intervention group (p < 0.002). There were no clinically significant differences in secondary outcomes. The pharmacist-driven penicillin allergy de-labeling pilot program in CT and spine surgery patients was associated with increased cefazolin use. Full article

The treatment of allergic conditions presents a challenge for both seasonal allergic rhinitis and perennial rhinitis sufferers. The increasing prevalence of both of these types of allergic responses requires the use of a range of treatments which can provide relief. The treatment of allergic rhinitis has been considered under the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines. Current treatment options include medication and avoidance for those with reduced responses, but more expensive treatments include immunotherapy and the use of monoclonal antibodies (mAb). All treatments target specific parts of the inflammatory response which includes mast cells, eosinophils and basophils. Phototherapy can be a useful addition to these treatments, and combinations of UV-B (5%), UV-A (25%) and visible light (70%) in phototherapy treatments have been shown to reduce the severity of symptoms. Phototherapy consisting of visible wavelengths and infrared light (660 nm 940 nm) was shown to be particularly effective in treating perennial rhinitis. The use of a range of wavelengths in the control of allergic responses is described in this paper. Phototherapy can form part of an effective treatment regime for allergic rhinitis sufferers which can exploit synergies in the control of the condition elicited through several pathways. Full article

Allergens are substances that cause abnormal immune responses and can originate from various sources. IgE-mediated allergies are one of the most common and severe types of allergies, affecting more than 20% of the population in Western countries. Allergens can be subdivided into a limited number of families based on their structure, but this does not necessarily indicate the origin or the route of administration of the allergen, nor is the molecular basis of allergenicity clearly understood. This review examines how understanding the allergenicity of proteins involves their structural characterization and elucidates the study of conformational diversity by nuclear magnetic resonance spectroscopy. This article also discusses allergen cross-reactivity and the mechanisms by which IgE antibodies recognize and bind to allergens based on their conformational and linear epitopes. In addition, we outline how the pH, the proteolytic susceptibility and the endosomal degradation affect the outcome of allergic reactions, and how this is correlated with conformational changes and secondary structure rearrangement events. We want to emphasize the importance of considering structural diversity and dynamics, proteolytic susceptibility and pH-dependent factors to fully comprehend allergenicity. Full article

Allergic rhinitis is the most common immune disorder worldwide, affecting approximately 10–40% of the general population. It is characterized by an inflammatory response of the nasal mucosa following exposure to non-infectious, inhaled, and airborne allergens that are defined based on the period of exposure to the allergen as annual, seasonal, or episodic. A variety of factors are found to relate to the prevalence of allergic rhinitis, i.e., sex, race, age, seasonality, personal and family-positive atopic history, as well as exposure to environmental and epigenetic factors. In addition to the local inflammation in the nasal mucosa, systemic inflammation is activated in the entire respiratory system, such as rhinoconjunctivitis, asthma, sinusitis, and otitis media with effusion. The aim of this study was to evaluate the trends in the prevalence of allergic rhinitis in the Greek pediatric and adolescent population since 1990. Research was performed in electronic databases (PubMed, ScienceDirect, and Cochrane Library) using appropriate MeSH terms for related studies from 1990 to 2023. We found 12 studies, 11 prospective and 1 cross-sectional, conducted in the cities of Athens, Thessaloniki, Patras and Evros prefecture, with sample sizes varying from 517 to 3076 subjects aged 6–17 years old. The prevalence of allergic rhinitis showed geographic and temporal variability, ranging between 2.1 and 32.5% in children and 25.3 and 30.8% in adolescents, with increasing trends. Factors such as gender (male), age (8–10 years), environmental exposures (moisture, mites, and fungi), positive atopic profile, and family history (asthma and eczema) were related to the manifestation of the disease. The need for systematic research in the Greek child and adolescent population is vital to recognize, prognosis, and control allergic rhinitis manifestations. Full article