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Introduction: Clinical recognition of potential immune-mediated allergic responses to implanted metal devices is increasing. For orthopaedic implants, while 'pure' compounds are used in specific circumstances, the majority of components are alloys - a combination of two or more distinct metals. Titanium is found commonly in many orthopaedic devices and is often championed as a 'hypoallergenic' option or inclusion. In the absence of a relevant previously published summary on the topic, this paper explores the current state-of-understanding of titanium allergy and proposes a patient management algorithm whereby such immune reactions are clinically-suggested., Methods: A structured, systematic literature review was performed following PRISMA search principles to provide a contemporary summary-of-understanding in this area and to highlight clinical and knowledge deficiencies., Results: Thirty-five topic-related articles were identified, the majority reflecting small case series' or proof-of-concept studies. The general standard of scientific evidence available was poor. Justification for arthroplasty utilization of titanium as a 'hypoallergenic' option is largely extrapolated from non-orthopaedic domains., Conclusions: Both ionic and conjugated titanium particles released from implant surfaces have the potential to trigger innate immune responses and true allergy. There exists no simple, high-sensitivity, screening test for titanium allergy. Conventional skin-patch testing is unreliable due to poor dermal penetration. Given established lymphocyte and macrophage activation pathways for allergy responses, in vitro methods using both cell-types show diagnostic promise. Surgical biopsy analysis from host-implant interfaces remains the contemporary 'gold-standard', however this represents an invasive, costly and highly-specialized approach not readily available in most settings. Further research to establish reliable/accessible diagnostic methods are indicated., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Objectives: This study aimed to document adverse health effects among office, copy, and print shop workers using the Nano-Control, International Foundation Survey., Methods: Self-reported information on 16 health outcomes and three surrogate exposure variables were collected from 1998 individuals between 1999 and 2010. Logistic regression models, adjusted for age, gender, and smoking status, assessed the association between printer exposure and health symptoms., Results: Among the participants, 61.9% were office workers, 5.5% were technicians, and 23.3% held other professions. Technicians had a higher risk for cancer compared to office workers (odds ratio [OR], 2.5; P < 0.01). Visible toner dust exposure was associated with chronic fatigue (OR, 9.6; P < 0.01), bronchial hyperresponsiveness (OR, 5.1; P < 0.01), cardiovascular diseases (OR, 3.6; P < 0.01), asthma, allergies, and other diseases (OR range, 1.4-3.2; P < 0.01)., Conclusions: The increased chronic and acute health risks among these workers warrant further investigations of causal associations., Competing Interests: Ethical considerations and disclosures: Data for all participants involved in this study were de-identified. As such, this work was exempt from the UML IRB. Authors A. Ojo, D. Bello, K. Heavner, K. Lucas, and A. Bello have no relationships/conditions/circumstances that present potential conflict of interest. Conflict of interest: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: Infant growth trajectories reflect current health status and may predict future obesity and metabolic diseases. Human milk is tailored to support optimal infant growth. However, nutrient intake rather than milk composition more accurately predicts growth outcomes. Although the role of protein leverage in infant growth is unclear, protein intake is important for early infancy growth., Materials and Methods: This study of exclusively breastfeeding mothers with allergies ( n = 161) from the Infant Fish Oil Supplementation Study assessed relationships between intake of human milk macronutrients and infant growth. Human milk fat, protein and lactose concentrations were measured at 3 months postpartum, and infant daily intakes were estimated using an average milk intake of 800 mL/day., Results: Higher human milk protein:energy ratio was associated with higher weight-for-age z-score at 2.5 years compared to 3 months and higher body mass index-for-age z-score change (6 months to 1 year compared to 3-6 months). Maternal atopy and birth season (summer) were negatively associated with human milk lactose concentration. Passive smoke exposure was associated with reduced energy and fat concentrations and increased lactose:energy ratio., Conclusions: Our results indicate that intake of human milk macronutrients may impact early childhood growth.

Background: Allergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood., Methods: We used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell-depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post-allergen challenge. Also, changes in serum triglycerides (TGs) were evaluated in a group of 59 patients ≥14 days after the onset of an allergic reaction., Results: We found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TGs and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T-cell-driven late phase inflammation. On the contrary, the IgG-mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TGs in 59 patients after undergoing an allergic reaction., Conclusion: Overall, this study reveals that IgG-mediated allergic inflammation regulates lipid metabolism., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Allergy to galactose-α-1,3-galactose (alpha-gal) is associated with immediate allergic manifestations and premature degeneration of the prosthesis in patients who receive bovine- or porcine-derived bioprosthetic valves. Here, we report a 72-year-old man with atrial fibrillation, aortic regurgitation, and severe alpha-gal allergy who presented for consideration of aortic valve replacement. He was premedicated with antihistamines and steroids and underwent aortic valve replacement with 25-mm INSPIRIS aortic valve (Edwards Lifesciences) and left atrial appendage occlusion with 40-mm AtriClip device (AtriCure), without immediate or short-term complications., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Early-life (EL) respiratory infections increase pulmonary disease risk, especially EL-Respiratory Syncytial Virus (EL-RSV) infections linked to asthma. Mechanisms underlying asthma predisposition remain unknown. In this study, we examined the long-term effects on the lung after four weeks post EL-RSV infection. We identified alterations in the lung epithelial cell, with a rise in the percentage of alveolar type 2 epithelial cells (AT2) and a decreased percentage of cells in the AT1 and AT2-AT1 subclusters, as well as upregulation of Bmp2 and Krt8 genes that are associated with AT2-AT1 trans-differentiation, suggesting potential defects in lung repair processes. We identified persistent upregulation of asthma-associated genes, including Il33. EL-RSV-infected mice allergen-challenged exhibited exacerbated allergic response, with significant upregulation of Il33 in the lung and AT2 cells. Similar long-term effects were observed in mice exposed to EL-IL-1β. Notably, treatment with IL-1ra during acute EL-RSV infection mitigated the long-term alveolar alterations and the allergen-exacerbated response. Finally, epigenetic modifications in the promoter of the Il33 gene were detected in AT2 cells harvested from EL-RSV and EL-IL1β groups, suggesting that long-term alteration in the epithelium after RSV infection is dependent on the IL-1β pathway. This study provides insight into the molecular mechanisms of asthma predisposition after RSV infection., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. To explore its pathophysiology, we investigated the association between neonatal allergic exposure and behavioral changes. Adult female C57BL/6J mice were immunized with adjuvant (aluminum hydroxide) or ovalbumin emulsified with adjuvant. After immunization, the mice were mated, and offspring were born at full term. The postnatal dams and infants were then simultaneously exposed to an allergen (ovalbumin) or vehicle via inhalation. After weaning, behavioral testing and histopathological analyses were conducted on male offspring. Compared with the vehicle-exposed offspring, the ovalbumin-exposed offspring had decreased sociability and increased repetitive behavior, thus representing an ASD-like phenotype in mice. Moreover, histopathological analyses revealed that the ovalbumin-exposed mice had increased astroglial, microglial, and eosinophilic infiltration in the olfactory bulb, as well as increased eosinophils in the nasal mucosa. The ovalbumin-exposed mice also had decreased dendritic spine density and a lower proportion of mature spines, suggesting the impairment of stimulus-induced synaptogenesis. In conclusion, postnatal allergic exposure induced an ASD-like phenotype, as well as allergic rhinitis, which was followed by glial inflammation in the olfactory bulb parenchyma.

Background: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined., Methods: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure., Results: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions., Conclusion: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Metal hypersensitivity is a rare and often underestimated complication, as shown by the small number of published studies, particularly concerning the upper limbs and the hand. However, the increase in the annual number of trapeziometacarpal arthroplasties underlines the importance of better understanding of this problem. We performed a study based on data from the revision of trapeziometacarpal prostheses to assess the incidence of this complication and to define a sequence of radiological changes to detect metal hypersensitivity. This single-center retrospective study included 37 patients operated on between January 2014 and November 2023 for revision of trapeziometacarpal prosthesis. Ten (27%) had no clearly identified cause of failure. For these 10 patients, we analyzed clinical data and postoperative X-rays. In the 11 revision arthroplasties, 2 patients had no symptoms or radiographic signs suggestive of allergy. Six patients had a-posteriori diagnosis established by allergy testing, which also identified 2 additional patients, for a total of 8 patients (21% of the initial cohort). In these cases, there was systematic metaphyseal osteolysis of the first metacarpal between 15 days and 1 month after implantation. Clinically, most patients had an asymptomatic period of 2 weeks to 1 month before onset of symptoms and osteolysis, often accompanied by local inflammation. This study found a reproducible pattern of progression, characterized by the appearance of radiographic signs of osteolysis in the first month, followed by clinical deterioration. Although this course is strongly suggestive of a metal hypersensitivity, it is crucial not to exclude the possibility of an infectious cause, which should always be considered., (Copyright © 2024 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Traffic-related air and noise pollution are important public health issues. The aim of this study was to estimate their effects on allergic/respiratory outcomes in adult and elderly subjects., Materials and Methods: Six hundred and forty-five subjects living in Pisa (Tuscany, Italy) were investigated through a questionnaire on allergic/respiratory symptoms and diseases. Traffic-related air pollution and noise exposures were assessed at residential address by questionnaire, modelled annual mean NO 2 concentrations (1 km and 200 m resolution), and noise level over a 24-h period (Lden). Exposure effects were assessed through logistic regression models stratified by age group (18-64 years, ≥65 years), and adjusted for sex, educational level, occupational exposure, and smoking habits., Results: 63.6% of the subjects reported traffic exposure near home. Mean exposure levels were: 28.24 (±3.26 SD ) and 27.23 (±3.16 SD ) µg/m 3 for NO 2 at 200 m and 1 km of resolution, respectively; 57.79 dB(A) (±6.12 SD ) for Lden. Exposure to vehicular traffic (by questionnaire) and to high noise levels [Lden ≥ 60 dB(A)] were significantly associated with higher odds of allergic rhinitis (OR 2.01, 95%CI 1.09-3.70, and OR 1.99, 95%CI 1.18-3.36, respectively) and borderline with rhino-conjunctivitis (OR 2.20, 95%CI 0.95-5.10, and OR 1.76, 95%CI 0.91-3.42, respectively) only in the elderly. No significant result emerged for NO 2 ., Conclusions: Our findings highlighted the need to better assess the effect of traffic-related exposure in the elderly, considering the increasing trend in the future global population's ageing.

Allergic diseases affect nearly 30% of people worldwide. There is a wide range of allergen sources, such as animal dander, food, venom, dust mites, and pollen. The skin prick test is the predominant technique used to identify allergenic sensitivity in vivo; the main problem is that it can be imprecise as many of the allergen extracts are made of mixtures of allergic and nonallergic components, making it difficult to identify the disease-eliciting allergen. An alternative to solve this problem is employing cellular models in vitro that may allow allergen identification, allergy diagnosis, and testing of novel potential compounds that can be used in immunotherapeutics. For example, rat basophilic leukemia (RBL) cells are a well-suited model for studying allergies. Unfortunately, cells generated from RBL cells are not commercially available. Therefore, we developed an RBL model with a degranulation gene reporter capable of recognizing human IgE involved in allergenic sensitivity using commercial plasmids. Employing this model, we successfully evaluated the capacity of union between IgE from allergic patients to allergenic proteins from Oleaceae tree pollen. This RBL cell model can be used as a diagnostic method for sensitivity to any allergens from different sources in vitro., (© 2024. The Author(s).)

Purpose: The aim of this study was to determine clinically and genetically the allergic effects of titanium and poly-ether-ether-ketone (PEEK) implants following loading in rabbit tibias., Materials and Methods: This study included 18 white New Zealand male rabbits (n = 18) divided evenly into three groups: control, titanium (Ti), and PEEK (P). Clinically, the allergenic effect of titanium and PEEK was investigated by detecting the effect on lymph nodes. Furthermore, RT-PCR and ELISA were used to detect the expression of certain genes IL-6, TNF-α, OPG, RANKL, and RUNX-2 through both types of implants., Results: Our findings demonstrated that titanium implants induced enlarged lymph nodes, which PEEK did not. Overall, RT-PCR and ELISA techniques revealed that Ti implants had higher expression of the inflammatory genes IL-6 and TNF-α. Ti had the highest expression in OPG findings, while PEEK had the lowest. RANKL expression was highest in the control group and lowest in the PEEK group. RUNX-2 is the highest for the control group and the lowest for the titanium group., Conclusion: Although titanium implants elicited greater allergy responses than PEEK implants, titanium has the highest expression of bone formation genes and the lowest expression of bone resorption genes, making it preferable to PEEK., (© 2024 Wiley Periodicals LLC.)

Allergic diseases affect up to 40% of the global population with a substantial rise in food allergies, in particular, over the past decades. For the majority of individuals with allergy fundamental programming of a pro-allergic immune system largely occurs in early childhood where it is crucially governed by prenatal genetic and environmental factors, including their interactions. These factors include several genetic aberrations, such as filaggrin loss-of-function mutations, early exposure to respiratory syncytial virus, and various chemicals such as plasticizers, as well as the influence of the gut microbiome and numerous lifestyle circumstances. The effects of such a wide range of factors on allergic responses to an array of potential allergens is complex and the severity of these responses in a clinical setting are subsequently not easy to predict at the present time. However, some parameters which condition a pro-allergic immune response, including severe anaphylaxis, are becoming clearer. This review summarises what we currently know, and don't know, about the factors which influence developing pro-allergic immunity particularly during the early-life perinatal period., (© 2024. The Author(s).)

Background: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes., Methods: Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments., Results: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels., Conclusions: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose of Review: Modernization and Westernization in industrialized and developing nations is associated with a substantial increase in chronic noncommunicable diseases. This transformation has far-reaching effects on lifestyles, impacting areas such as economics, politics, social life, and culture, all of which, in turn, have diverse influences on public health. Loss of contact with nature, alternations in the microbiota, processed food consumption, exposure to environmental pollutants including chemicals, increased stress and decreased physical activity jointly result in increases in the frequency of inflammatory disorders including allergies and many autoimmune and neuropsychiatric diseases. This review aims to investigate the relationship between Western lifestyle and inflammatory disorders., Recent Findings: Several hypotheses have been put forth trying to explain the observed increases in these diseases, such as 'Hygiene Hypothesis', 'Old Friends', and 'Biodiversity and Dysbiosis'. The recently introduced 'Epithelial Barrier Theory' incorporates these former hypotheses and suggests that toxic substances in cleaning agents, laundry and dishwasher detergents, shampoos, toothpastes, as well as microplastic, packaged food and air pollution damage the epithelium of our skin, lungs and gastrointestinal system. Epithelial barrier disruption leads to decreased biodiversity of the microbiome and the development of opportunistic pathogen colonization, which upon interaction with the immune system, initiates local and systemic inflammation. Gaining a deeper comprehension of the interplay between the environment, microbiome and the immune system provides the data to assist with legally regulating the usage of toxic substances, to enable nontoxic alternatives and to mitigate these environmental challenges essential for fostering a harmonious and healthy global environment., (© 2024. The Author(s).)

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.5, PM10, NO 2 , SO 2 , O 3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS-E tools and the certainty of the evidence by using GRADE. Short-term exposure to PM2.5, PM10, and NO 2 probably increases the risk of asthma-related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new-onset asthma in agricultural workers, while exposure to 1,3-dichloropropene may increase the risk of asthma-related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma-related ED visits and HA and asthma mortality (low certainty evidence)., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new-onset asthma (incidence) and (ii) adverse asthma-related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new-onset asthma and critical and important asthma-related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new-onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new-onset asthma and with asthma severity (low level of certainty). Exposure to pesticides and VOCs may increase the risk of new-onset asthma (very low certainty evidence). The impact on asthma-related outcomes of all major indoor pollutants is uncertain. As the level of certainty is low or very low for most of the available evidence on the impact of indoor pollutants on asthma-related outcomes more rigorous research in the field is warranted., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental stimuli. Allergic diseases showing a wide range of severity of symptoms have a significant impact on the quality of life of affected individuals. This study aims to highlight the mechanisms that induce these reactions, how they progress, and which prenatal factors influence their development. Most frequently, the reaction is mediated by immunoglobulin E (IgE) produced by B cells, which binds to the surface of mast cells and basophils and triggers an inflammatory response. The antibody response is triggered by a shift in T-cell immune response. The symptoms often start in early childhood with eczema or atopic dermatitis and progress to allergic asthma in adolescence. An important determinant of allergic diseases seems to be parental, especially maternal history of allergy. Around 30% of children of allergic mothers develop allergic sensitization in childhood. Genes involved in the regulation of the epithelial barrier function and the T-cell response were found to affect the predisposition to developing allergic disorders. Cord blood IgE was found to be a promising predictor of allergic disease development. Fetal B cells produce IgE starting at the 20th gestation week. These fetal B cells could be sensitized together with mast cells by maternal IgE and IgE-allergen complexes crossing the placental barrier via the low-affinity IgE receptor. Various factors were found to facilitate these sensitizations, including pesticides, drugs, exposure to cigarette smoke and maternal uncontrolled asthma. Prenatal exposure to microbial infections and maternal IgG appeared to play a role in the regulation of T-cell response, indicating a protective effect against allergy development. Additional preventive factors were dietary intake of vitamin D and omega 3 fatty acids as well as decreased maternal IgE levels. The effect of exposure to food allergens during pregnancy was inconclusive, with studies having found both sensitizing and protective effects. In conclusion, prenatal factors including genetics, epigenetics and fetal environmental factors have an important role in the development of allergic disorders in later life. Children with a genetic predisposition are at risk when exposed to cigarette smoke as well as increased maternal IgE in the prenatal period. Maternal diet during pregnancy and immunization against certain allergens could help in the prevention of allergy in predisposed children.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Kidney replacement therapies (KRTs) including hemodialysis (HD) are one of the treatment options for most of the patients with end-stage kidney disease. Although HD is vital for these patients, it is not hundred percent physiological, and various adverse events including hypersensitivity reactions may occur. Fortunately, these reactions are rare in total and less when compared to previous decades, but it is still very important for at least two reasons: First, the number of patients receiving kidney replacement treatment is increasing globally; and the cumulative number of these reactions may be substantial. Second, although most of these reactions are mild, some of them may be very severe and even lead to mortality. Thus, it is very important to have basic knowledge and skills to diagnose and treat these reactions. Hypersensitivity reactions can occur at any component of dialysis machinery (access, extracorporeal circuit, medications, etc.). The most important preventive measure is to avoid the allergen. However, even with very specific test, sometimes the allergen cannot be found. In mild conditions, HD can be contained with non-specific treatment (topical creams, antihistaminics, corticosteroids). In more severe conditions, treatment must be stopped immediately, blood should not be returned to patient, drugs must be stopped, and rules of general emergency treatment must be followed., (© 2024 Wiley Periodicals LLC.)

Background: Metal allergy following placement of a metal pectus bar for minimally invasive repair of pectus excavatum (MIRPE) is a rare complication with potentially significant morbidity. There is no consensus regarding preoperative metal allergy testing (MAT). This study aims to assess incidence of metal allergy and titanium bar use in tested and untested patients and trends in MAT with different approaches to MAT., Methods: A retrospective chart review was performed on patients who underwent MIRPE from July 2009 to June 2022 at a single institution. During this time, MAT was performed routinely (RT; routine testing) and selectively (ST; selective testing)., Results: The cohort included 741 patients for analysis. Metal bar allergy was documented in 1.3 % of all patients; the incidence was 1.3 % in patients with MAT and 1.4 % without MAT. The incidence of bar allergy was 1.1 % in the RT group and 1.6 % in the ST group. In the RT group, bar allergy occurred in 1.4 % (3/216) of patients with a negative MAT. In the ST group, bar allergy occurred in 1.2 % (2/164) of patients with a negative MAT and in 1.9 % (3/162) of untested patients with a stainless-steel bar. Titanium bar use was not significantly different between the RT and ST groups (18.3 % vs 16.3 %, p > 0.05)., Conclusion: The incidence of metal bar allergy after MIRPE was less than 2 %, and titanium bar use was not significantly different in routine and selective testing groups. MAT was not associated with a reduction in bar allergy, and its use remains unsupported., Level of Evidence: III., Competing Interests: Conflict of interest DMN is a consultant for Atricure and KLS and has patents related to pectus excavatum repair. BEP is a consultant for Atricure. LEM has received honoraria for speaking and teaching with Atricure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Several risk factors have been identified for the development of postoperative shoulder stiffness, and there has been increasing interest in orthopedic literature regarding patient-reported allergy (PRA) as an identifiable risk factor for adverse outcomes. The purpose of this study is to determine whether PRAs are associated with subsequent rates of diagnosis of adhesive capsulitis (AC) or return to the operating room for postoperative shoulder stiffness within 2 years after arthroscopic rotator cuff repair (ARCR)., Methods: Current Procedural Terminology surgical billing codes were used to retrospectively identify patients who underwent ARCR at a single urban academic institution from January 2012 to December 2020 with minimum 2-year follow-up. Lysis of adhesions (LOA), manipulation under anesthesia (MUA), and AC of the shoulder were further queried within 2 years postoperatively for the ipsilateral shoulder. Patients were excluded if they had undergone ipsilateral MUA/LOA or received a diagnosis of AC before the index procedure. Demographic characteristics and medical comorbidities (hypertension, diabetes, hyperlipidemia, and hypothyroidism) were extracted from electronic medical records. Baseline characteristics were compared between patients with and without PRAs. Multivariate logistic regression analyses were performed to determine the association of the presence of PRAs overall, as well as the presence of 1, 2, or 3 or more PRAs, with subsequent MUA/LOA or diagnosis of AC within 2 years postoperatively., Results: Of 7057 patients identified in the study period, 6583 were eligible for the final analysis. The mean age was 56.6 ± 11.7 years, and the mean body mass index was 29.1 ± 5.6. Overall, 19.3% of patients (n = 1271) reported at least 1 allergy, and 7.1% (n = 469) had >1 PRA. A total of 44 patients (0.7%) underwent subsequent ipsilateral MUA/LOA within 2 years postoperatively, whereas 93 patients (1.4%) received a diagnosis of ipsilateral AC in the same time frame. PRAs were significantly associated with subsequent diagnosis of AC (odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.45-3.92; P < .001), but not MUA/LOA (OR: 1.97, 95% CI: 1.26-3.61; P = .133). Patients with 2 PRAs had greater odds of being diagnosed with AC than patients with 1 PRA (OR: 2.74; 95% CI: 1.14-5.99; P = .012). Although this association was nonsignificant for MUA/LOA, patients with 2 PRAs (OR: 2.67; 95% CI: 0.96-8.80; P = .059) demonstrated a similar statistical trend., Conclusion: PRAs are associated with increased odds of receiving a diagnosis of AC within 2 years after ARCR but were not found to be associated with return to the operating room for postoperative stiffness., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

This systematic review aims to identify the association between prenatal exposure to air pollutants and allergic diseases in children, focusing on specific pollutants, timing of exposure, and associated diseases. We searched PubMed, Scopus, and Web of Science for English articles until May 1, 2023, examining maternal exposure to outdoor air pollutants (PM 1 , PM 2.5 , PM 10 , NO, NO 2 , SO 2 , CO, and O 3 ) during pregnancy and child allergic diseases (atopic dermatitis (AD), food allergy (FA), asthma (AT) and allergic rhinitis (AR)/hay fever (HF)). The final 38 eligible studies were included in the meta-analysis. Exposure to PM 2.5 and NO 2 during pregnancy was associated with the risk of childhood AD, with pooled ORs of 1.34 (95% confidence interval (CI), 1.10-1.63) and 1.10 (95%CI, 1.05-1.15) per 10 µg/m 3 increase, respectively. Maternal exposure to PM 1 , PM 2.5 , and NO 2 with a 10 µg/m 3 increase posed a risk for AT, with pooled ORs of 1.34 (95%CI, 1.17-1.54), 1.11 (95%CI, 1.05-1.18), and 1.07 (95%CI, 1.02-1.12), respectively. An increased risk of HF was observed for PM 2.5 and NO 2 with a 10 µg/m 3 increase, with ORs of 1.36 (95%CI, 1.17-1.58) and 1.26 (95%CI, 1.08-1.48), respectively. Traffic-related air pollutants (TRAP), particularly PM 2.5 and NO 2 , throughout pregnancy, pose a pervasive risk for childhood allergies. Different pollutants may induce diverse allergic diseases in children across varying perinatal periods. AT is more likely to be induced by outdoor air pollutants as a health outcome. More research is needed to explore links between air pollution and airway-derived food allergies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Scope: Edible insects contain allergens with potential cross-reactivity to other invertebrates. Here, this study examines IgE-reactive proteins in a house cricket snack (Acheta domesticus) leading to an allergic reaction in a 27-year old man followed by a similar reaction days later after eating shrimps., Methods and Results: Prick to prick tests verify the IgE-mediated allergy to crickets and skin prick testing confirms a type I sensitization to house dust mite without any clinical relevance for the patient, and to shrimp extracts, but is negative for several other foods. Serological testing reveals a sensitization to shrimps, shrimp tropomyosin, and house dust mite tropomyosin. IgE-immunodetection shows that the cricket allergic patient is sensitized to two proteins of 45 and >97 kDa using aqueous control cricket extract, but to only one protein at around 45 kDa when using the causative, seasoned insect snack extract. Mass spectrometry data and IgE-inhibition experiments clearly identify this protein belonging to the tropomyosin allergen family., Conclusion: This case report suggests that cricket tropomyosin may be an elicitor of allergic reactions even in previously not allergic patients, although it cannot be excluded the patient reacted additionally to other ingredients of the snack., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Background: Metal allergy remains a controversial topic in the orthopaedic community. It is not known if or to what degree metal sensitivity contributes to inflammatory soft tissue failures, unexplained residual pain, or clinical complications after total joint replacement with metal prostheses., Methods: We investigated the efficacy of the lymphocyte transformation test (LTT) in predicting adverse outcomes in patients after receiving a metal joint replacement. Our study cohort consists of 135 metal-on-metal hip resurfacing arthroplasty cases performed between 2013 and 2015. All study patients had an LTT preoperatively. We retrospectively analyzed clinical outcomes and failures for our cohort., Results: There was no difference in LTT reactivity between men and women. Of the 135 patients tested, 46 (34.1% of cohort) tested positive to at least one of the materials comprising their implant, and 78 patients (57.8%) had at least one reactive score to any component of the LTT. After a minimum follow-up of two years, we did not observe an allergic response to the implant in any patients. There were no failures requiring revision. We observed a 2.2% rate of moderate residual pain; no patients with residual pain tested positive for metal sensitivity. When patients with moderate-high LTT reactivity (30.4% of cohort) were compared to the remainder of the study group, there was no difference in HHS or UCLA activity score. There was no correlation between blood metal ion levels and LTT reactivity., Conclusion: We were unable to prove any predictive value of the LTT. We failed to identify hypersensitivity to metals in patients with metal-on-metal hip resurfacing arthroplasty., (© 2023. The Author(s).)

Allergic diseases have risen sharply in recent decades. After some epidemiological data, we take a look at the various hypotheses explaining this allergy "epidemic". Changes in our environment, such as pollution, are a source of climate change and an increase in allergic diseases through inflammation of epithelial barriers. Allergy prevention, a public health emergency, relies on environmental actions at both individual and collective levels., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Allergic diseases (ADs) have been increasingly reported in infants and children over the last decade. Diet, especially the inclusion of fish intake, may help to lower the risk of ADs. However, fish also, can bioaccumulate environmental contaminants such as mercury. Hence, our study aims to determine what effects the type and frequency of fish intake have on ADs in six-month-old infants, independently and jointly with mercury exposure., Methods: This study is part of the prospective birth cohort: Mothers and Children's Environmental Health (MOCEH) study in South Korea. Data was collected on prenatal fish intake, prenatal mercury concentration and ADs for infants aged six months for 590 eligible mother-infant pairs. Logistic regression analysis was conducted to evaluate the risk of prenatal fish intake and mercury concentration on ADs in infants. Finally, interaction between fish intake and mercury concentration affecting ADs in infants was evaluated. Hazard ratios of prenatal fish intake on ADs in 6 month old infants were calculated by prenatal mercury exposure., Results: Logistic regression analysis showed that white fish (OR: 0.53; 95% CI 0.30-0.94; P < 0.05) intake frequency, once a week significantly decreased the risk of ADs in infants. Stratification analysis showed that consuming white fish once a week significantly reduced the hazard of ADs (HR: 0.44; 95% CI 0.21-0.92; P < 0.05) in infants in the high-mercury (≥ 50th percentile) exposure group., Conclusion: The result indicates that prenatal white fish intake at least once a week reduces the risk of ADs in infants, especially in the group with high prenatal mercury exposure., (© 2024. The Author(s).)

Background: Hemodialysis reactions (HDRs) are similar to complement activation-related pseudo allergy (CARPA), a hypersensitivity reaction that occurs when administering certain (nano)drugs intravenously. The pathomechanism of CARPA was described based on animal experiments. Typical CARPA-like dialysis reactions, which occur at the start of hemodialysis, have been reported using polysulfone dialyzers. However, to our knowledge, this is the first dialysis reaction that occurred towards the end of hemodialysis treatment., Case Presentation: This report describes a 52-year-old Caucasian male patient who had been receiving chronic hemodialysis for 3 years and exhibited a CARPA reaction during his third hour of treatment. Upon activation of the microbubble alarm, the extracorporeal system recirculated for five minutes. Following reconnection, the patient exhibited a drop in systemic blood pressure, chest pain, and dyspnea after five minutes. Symptoms disappeared spontaneously after reducing the speed of the blood pump, placing the patient in a Trendelenburg position, and administering a bolus infusion from the dialysis machine. The remaining dialysis treatment was uneventful., Conclusion: Numerous case reports about reactions occurring with modern high-efficiency polysulfone dialyzers have been published. However, due to changes in the material structure by the manufacturers, we have not encountered such cases lately. The recently reported increase in thromboxane-B2 and pulmonary arterial pressure and complement activation upon re-infusion of extracorporeal blood following dialysis may explain the reaction observed here., (© 2024. The Author(s).)

Climate change is a major threat to human respiratory health and associated allergic disorders given its broad impact on the exposome. Climate change can affect exposure to allergens, such as pollen, dust mites, molds, as well as other factors such as temperature, air pollution, and nutritional factors, which synergistically impact the immune response to these allergens. Exposome change can differentially exacerbate allergic reactions across subgroups of populations, especially those who are more vulnerable to environmental stressors. Understanding links between climate change and health impacts can help inform how to protect individuals and vulnerable populations from adverse health effects., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Simple plasma exchange (PE) with fresh-frozen plasma replacement allows antibody removal for ABO-incompatible living donor kidney transplantation, but is associated with a high incidence of allergic reactions. We developed, implemented, and evaluated a protocol for safe preoperative PE., Methods: The protocol comprised pretreatment (125 mg methylprednisolone infusion, 400 mg acetaminophen and 30 mg diphenhydramine orally) with a replacement fluid rate < 20 mL/min. Allergic reaction incidence was investigated in controls who underwent ABO-incompatible living donor kidney transplantation between 2016 and March 2020 (group C) and patients who underwent the protocol and procedure between April 2020 and February 2023 (group N)., Results: Ten (group C) and 19 (group N) patients performed 11 and 30 sessions of PE, respectively. Allergic reactions occurred in 81.8% and 36.7% (p = 0.014), respectively, with an odds ratio of the protocol was 0.056 (95% CI 0.0059-0.5380, P = 0.013)., Conclusion: Our protocol resulted in a significantly lower incidence of allergic reactions., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Asthma and allergic disorders are common in childhood with genetic and environmental determinants of disease that include prenatal nutritional exposures such as long-chain polyunsaturated fatty acids and antioxidants. Global climate change is implicated in asthma and allergic disorder morbidity with potential mechanisms including perturbations of ecosystems. There is support that environmental and climatic changes such as increasing global temperate and carbon dioxide levels affect aquatic and agricultural ecosystems with subsequent alterations in long-chain polyunsaturated fatty acid availability and nutrient quality and antioxidant capacity of certain crops, respectively. This article discusses asthma epidemiology and the influence of global climate change., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Asthma and allergies are some of the most common chronic disorders affecting children, the prevalence of which has been increasing in countries and regions undergoing rapid development like China. To curb the rising tide of allergies and safeguard the health of future generations, it is of critical importance to understand how asthma inception is influenced by factors acting at different life stages. Birth cohorts represent a powerful tool to investigate the temporal sequence of exposures along the natural course of asthma. We examined recent evidence on birth cohort studies of asthma and allergic diseases and evaluated their strengths and weaknesses. Essential elements for a successful birth cohort are proposed to further elucidate asthma etiology and pathogenies. Initiating new cohorts in understudied populations with the application of advanced analytical approaches will be needed. Moreover, fostering collaborative networks using standardized methodologies should be prioritized to enable integration of findings across diverse cohorts. There remains an urgent and unmet need to further translate the seminal findings from asthma birth cohort studies into targeted primary prevention strategies to eradicate the disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area., Methods: We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years., Results: We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively., Conclusion: Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)