Applying the dissemination and implementation sciences to allergy and immunology: A Work Group Report from the AAAAI Quality, Adherence, and Outcomes Committee.

Translating evidence-based practice (EBP) into real-world clinical settings often takes a considerable amount of time and resources. In allergy and immunology, the dissemination and implementation (D&I) sciences facilitate the study of how variations in knowledge, resources, patient populations, and staffing models lead to differences in the clinical care of asthma, allergic disease, and primary immunodeficiency. Despite the need for validated approaches to study how to best apply EBP in the real world, the D&I sciences are underutilized. To address this gap, an American Academy of Allergy, Asthma & Immunology (AAAAI) work group was convened to provide an overview for the role of the D&I sciences in clinical care and future research within the field. For the D&I sciences to be leveraged effectively, teams should be multidisciplinary and inclusive of community and clinical partners, and multimethods approaches to data collection and analyses should be used. Used appropriately, the D&I sciences provide important tools to promote EBP and health equity as well as optimization of clinical practice in allergy and immunology.

Control of Asthma and Allergy by Regulatory T Cells.

BACKGROUND: Epithelial barriers, such as the lungs and skin, face the challenge of providing the tissues' physiological function and maintaining tolerance to the commensal microbiome and innocuous environmental factors while defending the host against infectious microbes. Asthma and allergic diseases can result from maladaptive immune responses, resulting in exaggerated and persistent type 2 immunity and tissue inflammation. SUMMARY: Among the diverse populations of tissue immune cells, CD4+ regulatory T cells (Treg cells) are central to controlling immune responses and inflammation and restoring tissue homeostasis. Humans and mice that are deficient in Treg cells experience extensive inflammation in their mucosal organs and skin. During past decades, major progress has been made toward understanding the immunobiology of Treg cells and the molecular and cellular mechanisms that control their differentiation and function. It is now clear that Treg cells are not a single cell type and that they demonstrate diversity and plasticity depending on their differentiation stages and tissue environment. They could also take on a proinflammatory phenotype in certain conditions. KEY MESSAGES: Treg cells perform distinct functions, including the induction of immune tolerance, suppression of inflammation, and promotion of tissue repair. Subsets of Treg cells in mucosal tissues are regulated by their differentiation stage and tissue inflammatory milieu. Treg cell dysfunction likely plays roles in persistent immune responses and tissue inflammation in asthma and allergic diseases.

Micronutrients and Allergic Diseases: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have indicated a controversy regarding the association between dietary micronutrient concentrations and the risk of allergic diseases. In this study, we employed Mendelian randomization (MR) analysis using data from two samples to investigate the causal relationship between circulating micronutrient concentrations and three allergic diseases. METHODS: In this study, we considered 16 circulating micronutrients as exposure variables (beta carotene, calcium, copper, folate, iron, lycopene, magnesium, phosphorus, selenium, vitamin A1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and zinc); and three common allergic diseases (allergic asthma [AA], atopic dermatitis [AD], and allergic rhinitis [AR]) as outcomes. The inverse variance weighted (IVW) method was primarily applied for MR analysis, supplemented by MR-Egger and weighted-median methods to corroborate the IVW results; and sensitivity analysis was conducted to ensure the robustness of the MR assumptions. RESULTS: Our results revealed that an increase in serum phosphorus and zinc concentrations may diminish the risk of AA, while for AD an increase in serum zinc concentration may reduce the risk, but an increase in serum vitamin C concentration may elevate the risk. As for AR, an increase in serum phosphorus and selenium concentrations appeared to be associated with a reduced risk. We did not find evidence for an association between other micronutrients and the risk of allergic diseases. CONCLUSION: Our study indicates that an increase in serum phosphorus and zinc concentrations may reduce the risk of AA, while an increase in serum zinc concentration may reduce the risk of AD, but an increase in serum vitamin C concentration may elevate the risk of AD. An increase in serum phosphorus and selenium concentrations is associated with a reduced risk of AR. This provides additional support for research on the effects of micronutrients on allergic diseases.

Unraveling the role of NLRP3 inflammasome in allergic inflammation: implications for novel therapies.

Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1ß and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1ß, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3's specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases.

Climate change from the Asia-Pacific perspective: What an allergist needs to know and do.

Allergic diseases such as asthma, atopic dermatitis, and food allergies are a burgeoning health challenge in the Asia-Pacific region. Compounding this, the region has become increasingly susceptible to the impacts of climate change. The region has weathered extreme precipitation, intense heat waves, and dust storms over the recent decades. While the effects of environmental and genetic factors on allergic diseases are well understood, prevailing gaps in understanding the complex interactions between climate change and these factors remain. We aim to provide insights into the various pathways by which climate change influences allergic diseases in the Asia-Pacific population. We outline practical steps that allergists can take to reduce the carbon footprint of their practice on both a systemic and patient-specific level. We recommend that allergists optimize disease control to reduce the resources required for each patient's care, which contributes to reducing greenhouse gas emissions. We encourage the responsible prescription of metered dose inhalers by promoting the switch to dry powder inhalers for certain patients, at each clinician's discretion. We also recommend the utilization of virtual consultations to reduce patient travel while ensuring that evidence-based guidelines for rational allergy management are closely adhered to. Finally, eliminating unnecessary testing and medications will also reduce greenhouse gas emissions in many areas of medical care.

Association of Soda Drinks and Fast Food with Allergic Diseases in Korean Adolescents: A Nationwide Representative Study.

INTRODUCTION: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis). METHODS: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food. RESULTS: Among 865,614 adolescents in grades 7-12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03-1.12) and fast food consumption (1.25; 1.17-1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19-1.44) and fast food (1.46; 1.26-1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks. CONCLUSION: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs.

A review of common influencing factors and possible mechanisms associated with allergic diseases complicating tic disorders in children.

Over the past few decades, the incidence of childhood allergic diseases has increased globally, and their impact on the affected child extends beyond the allergy itself. There is evidence of an association between childhood allergic diseases and the development of neurological disorders. Several studies have shown a correlation between allergic diseases and tic disorders (TD), and allergic diseases may be an important risk factor for TD. Possible factors influencing the development of these disorders include neurotransmitter imbalance, maternal anxiety or depression, gut microbial disorders, sleep disturbances, maternal allergic status, exposure to tobacco, and environmental factors. Moreover, gut microbial disturbances, altered immunological profiles, and DNA methylation in patients with allergic diseases may be potential mechanisms contributing to the development of TD. An in-depth investigation of the relationship between allergic diseases and TD in children will be important for preventing and treating TD.

Experimental Insights on the Use of Secukinumab and Magnolol in Acute Respiratory Diseases in Mice.

This study investigates the combined treatment of secukinumab (SECU) and magnolol (MAGN) in a mouse model of LPS-induced ALI overlapped with allergic pulmonary inflammation, aiming to better understand the mechanism behind this pathology and to assess the therapeutic potential of this novel approach in addressing the severity of ALI. The combined treatment reveals intricate immunomodulatory effects. Both treatments inhibit IL-17 and promote M2 macrophage polarization, which enhances anti-inflammatory cytokine production such as IL-4, IL-5, IL-10, and IL-13, crucial for lung repair and inflammation resolution. However, the combination treatment exacerbates allergic responses and increases OVA-specific IgE, potentially worsening ALI outcomes. MAGN pretreatment alone demonstrates higher potency in reducing neutrophils and enhancing IFN-γ, suggesting its potential in mitigating severe asthma symptoms and modulating immune responses. The study highlights the need for careful consideration in therapeutic applications due to the combination treatment's inability to reduce IL-6 and its potential to exacerbate allergic inflammation. Elevated IL-6 levels correlate with worsened oxygenation and increased mortality in ALI patients, underscoring its critical role in disease severity. These findings offer valuable insights for the advancement of precision medicine within the realm of respiratory illnesses, emphasizing the importance of tailored therapeutic strategies.

Impact of temperature and relative humidity variability on children's allergic diseases and critical time window identification.

BACKGROUND: The effects of temperature and relative humidity on different types of children's allergic diseases have not been comprehensively evaluated so far. This study aims to assess the impact of temperature and relative humidity variability on children's allergic diseases and to identify the critical time window. METHODS: We collected outpatient data on allergen testing in children between July 2020 and January 2022 from the Affiliated Children's Hospital of Nanjing Medical University. We defined the 1st, 10th, 90th, and 99th percentiles as extreme cold, moderate cold, moderate hot, and extreme hot for temperature, and as low, moderate high, and extreme high for relative humidity, respectively. A distributed lag nonlinear model (DLNM) combined with a binomial regression model was used to assess the possible nonlinear relationship at different periods. Subgroup analysis by gender and age was conducted. RESULTS: We found that extreme and moderate cold temperatures were positively associated with skin allergies and total allergies (28 days: OR = 4.69, 95% CI: 2.88, 7.63; OR = 3.36, 95% CI: 2.39, 4.73) and (28 days: OR = 3.76, CI: 2.43, 5.81; OR = 2.71, 95% CI: 2.00, 3.68), respectively. Moderate and extreme hot temperatures were negatively associated with food allergies (28 days: OR = 0.13, 95% CI: 0.04, 0.41 and OR = 0.04; 95% CI: 0.01, 0.27). Low relative humidity was negatively associated with respiratory allergies, skin allergies, and total allergic diseases (28 days: OR = 0.26, 95% CI: 0.10, 0.71; OR = 0.29, 95% CI: 0.15, 0.55; and OR = 0.42, 95% CI: 0.26, 0.68). Meanwhile, extreme high relative humidity was negatively associated with respiratory allergies, and positively associated with skin allergies, food allergies, and total allergies (28 days: OR = 0.16, 95%CI: 0.07, 0.37; OR = 3.60, 95% CI: 2.52, 5.14; OR = 15.61, 95% CI: 3.23, 75.56; and OR = 2.33, 95% CI: 1.73, 3.15). A stronger relationship between temperature, relative humidity, and allergic diseases was observed in children under 5 years, specifically girls. CONCLUSIONS: Our study provides evidence that temperature and relative humidity variability may be associated with allergic diseases, however, the directionality of the relationship differs by allergic type.

Allergic diseases and Meniere's disease: a bidirectional Mendelian randomization.

OBJECTIVES: Allergic diseases and Meniere's disease found to have a possible link in observational study. However, the potential causal relationship between the two is unclear. Therefore, we aimed to explore the causal relationship between allergic diseases and Meniere's disease using a new data analysis technique called bidirectional Mendelian randomization study. METHOD: Summary-level statistics for Meniere's disease and three allergic diseases (asthma, allergic rhinitis, eczema/dermatitis) were obtained from large-scale genome-wide association studies. The inverse variance weighted method was used as the primary measure, supplemented by MR-Egger regression and the weighted median method. To ensure the reliability of the conclusions, Cochran's Q, MR-Egger intercept, MR-PRESSO test, leave-one-out test, and MR Steiger test were used. RESULTS: Inverse-variance weighted method showed asthma (p = 0.008, OR = 3.908, 95% CI 1.424-10.724, adjust_p = 0.024), allergic rhinitis (p = 0.026, OR = 24.714, 95% CI 1.479-412.827, adjust_p = 0.026) and eczema/dermatitis (p = 0.019, OR = 3725.954, 95% CI 3.795 to 3,658,399.580, adjust_p = 0.029) all had a significant effect on Meniere's disease. Reverse Mendelian randomization studies have shown that Meniere's disease does not increase the risk of three allergic diseases. Sensitivity analysis showed no horizontal pleiotropy and heterogeneity for each trait. CONCLUSION: Our Mendelian randomization analysis supports a positive causal relationship between three allergic diseases (asthma, allergic rhinitis, eczema/dermatitis) and Meniere's disease. This suggests that physicians should pay more attention to the Meniere's patient's allergy history and consider allergy avoidance as part of their treatment plan. LEVEL OF EVIDENCE: Mendelian Randomized (MR) studies are second only to randomized controlled trials in terms of the level of evidence.

The role of deacetylase SIRT1 in allergic diseases.

The silent information regulator sirtuin 1 (SIRT1) protein is an NAD+-dependent class-III lysine deacetylase that serves as an important post-transcriptional modifier targeting lysine acetylation sites to mediate deacetylation modifications of histones and non-histone proteins. SIRT1 has been reported to be involved in several physiological or pathological processes such as aging, inflammation, immune responses, oxidative stress and allergic diseases. In this review, we summarized the regulatory roles of SIRT1 during allergic disorder progression. Furthermore, we highlight the therapeutic effects of targeting SIRT1 in allergic diseases.

Nonelective cesarean section is associated with the prevalence of asthma among Mexican children who attended childcare centers.

Background: The cesarean section (CS) mode of delivery can influence the prevalence of bronchial asthma (BA), allergic rhinitis (AR), or atopic dermatitis (AD) by promoting modifications in the infantile microbiome. Objective: To analyze the prevalence of asthma in children who were born through CS and attended childcare centers. Methods: The data were obtained through an online survey that was answered anonymously by one of the parents; the survey inquired about the route of delivery of the child and the prevalence of BA, AR, and AD. Results: A total of 525 children were included. The frequency of births by vaginal, elective CS, or nonelective CS was 34.1%, 37.9%, and 28.0%, respectively, and the prevalence of BA, AR, and AD was 4.8%, 19.8%, and 12.4%, respectively. Multivariate analyses identified nonelective CS as a factor associated with the prevalence of BA (odds ratio: 3.51, P = 0.026). Conclusion: Our study shows that being born through nonelective CS can increase the probability of BA in children who attended daycare centers.

Biodegradable Mesoporous Organosilica-Based Nanostabilizer Targeting Mast Cells for Long-Term Treatment of Allergic Diseases.

Allergic diseases are immune system dysfunctions mediated by mast cell (MC) activation stimulated by specific allergens. However, current small molecular MC stabilizers for allergic disease prevention often require multiple doses over a long period of time and are associated with serious side effects. Herein, we develop a diselenide-bridged mesoporous silica nanostabilizer, proving that it could specifically target sensitized MCs via the recognition of IgE aptamer and IgE. Meantime, the IgE aptamer can also mitigate allergic reactions by preventing re-exposure of allergens from the surface of sensitized MCs. Furthermore, the diselenide-bridged scaffold can be reduced by the intracellular excessive ROS, subsequently achieving redox homeostasis via ROS depletion. Finally, the precise release of small molecular MC stabilizers along with the biodegradation of nanocarrier can stabilize the membranes of MCs. In vivo assays in passive cutaneous anaphylactic (PCA) and allergic rhinitis (AR) mice indicated that our current strategy further endowed it with a high efficacy, long-term therapeutic time window, as well as negligible inflammatory side effects for allergic diseases, offering a promising therapeutic strategy for the clinical generalization of allergic diseases.

Cellular metabolism and hypoxia interfacing with allergic diseases.

Allergic diseases display significant heterogeneity in their pathogenesis. Understanding the influencing factors, pathogenesis, and advancing new treatments for allergic diseases is becoming more and more vital as currently, prevalence continues to rise, and mechanisms of allergic diseases are not fully understood. The upregulation of the hypoxia response is linked to an elevated infiltration of activated inflammatory cells, accompanied by elevated metabolic requirements. An enhanced hypoxia response may potentially contribute to inflammation, remodeling, and the onset of allergic diseases. It has become increasingly clear that the process underlying immune and stromal cell activation during allergic sensitization requires well-tuned and dynamic changes in cellular metabolism. The purpose of this review is to examine current perspectives regarding metabolic dysfunction in allergic diseases. In the past decade, new technological platforms such as "omic" techniques have been applied, allowing for the identification of different biomarkers in multiple models ranging from altered lipid species content, increased nutrient transporters, and altered serum amino acids in various allergic diseases. Better understanding, recognition, and integration of these alterations would increase our knowledge of pathogenesis and potentially actuate a novel repertoire of targeted treatment approaches that regulate immune metabolic pathways.

Risk of Asthma and Allergies in Children Delivered by Cesarean Section: A Comprehensive Systematic Review.

BACKGROUND: It is unclear whether cesarean delivery increases the risk of allergic diseases in offspring. OBJECTIVE: To investigate the association between cesarean delivery and the risk of allergic diseases in offspring. METHODS: We searched PubMed, Embase, and the Cochrane Library for relevant studies up to October 12, 2023. Observational studies comparing the risk of allergic diseases in offspring delivered by cesarean section versus those delivered vaginally were included. Most-adjusted estimates from individual studies were synthesized by meta-analysis. RESULTS: A total of 113 studies were included, 70 of which had a low risk of bias. Compared with offspring delivered vaginally, offspring delivered by cesarean section had significantly greater risks of asthma (odds ratio [OR] = 1.20; 95% CI, 1.16-1.25), allergic rhinitis or conjunctivitis (OR = 1.15' CI 1.09-1.22), atopic dermatitis or eczema (OR = 1.08; CI, 1.04-1.13), food allergies (OR = 1.35; CI, 1.18-1.54), and allergic sensitization (OR = 1.19; CI, 1.10-1.28). Cesarean delivery did not significantly increase urticaria risk. Sensitivity analyses including only studies with a low risk of bias, adjusted estimates, prospective data collection, large sample sizes, or outcomes from medical records generally supported these findings. Offspring age, study region latitude, economy type, and cesarean delivery rate accounted for some of the clinical heterogeneity. We found no data on allergic purpura. CONCLUSIONS: Most-adjusted estimates suggest that cesarean delivery is associated with increased risks of asthma, allergic rhinitis or conjunctivitis, atopic dermatitis or eczema, food allergies, and allergic sensitization in offspring. The impact of cesarean delivery on urticaria and purpura remains uncertain.

Association between allergic diseases and both psoriasis and psoriatic arthritis: a bidirectional 2-sample Mendelian randomization study.

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863-0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843-0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829-0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996-0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted.

Knowledge mapping of links between dendritic cells and allergic diseases: A bibliometric analysis (2004-2023).

In this study, bibliometric analysis was carried out to comprehend the global research trends, hotspots, scientific frontiers, and output characteristics of the links between dendritic cells (DCs) and allergic diseases from 2004 to 2023. Publications and their recorded information were retrieved from the Web of Science Core Collection (WoSCC). VOSviewer and Citespace were used to visualize the hotspots and trends of research area. ChemBio 3D, Autodock tools, and Discovery Studio were used to visualize the molecular docking results of hotspots. A total of 4861 articles were retrieved. The number of publications (Np) was in a high and stable state. Years 2011 and 2017 were two peaks in Np. The largest contributor in terms of publications, scholars, and affiliations was the USA. The paper published in NATURE MEDICINE (IF: 82.9) and written by Trompette, A in 2006 had the highest global citation score (GCS). Keywords, such as "asthma," "t-cells," "inflammation," "expression," "atopic dermatitis," "food allergy," "gut microbiota," "murine model," and "cytokines related to immunity" appeared the most frequently. Most of the binding free energy of the key active components of Saposhnikovia divaricata docked with toll-like receptor proteins well. This bibliometric study aimed to help better comprehend the present state and make decisions from a macro viewpoint.

The role of Interleukin-21 (IL-21) in allergic disorders: Biological insights and regulatory mechanisms.

In recent decades, allergic diseases subsequent from an IgE-mediated response to specific allergens have become a progressively public chronic disease worldwide. They have shaped an important medical and socio-economic burden. A significant proportion of allergic disorders are branded via a form 2 immune response relating Th2 cells, type 2 natural lymphoid cells, mast cells and eosinophils. Interleukin-21 (IL-21) is a participant of the type-I cytokine family manufactured through numerous subsets of stimulated CD4+ T cells and uses controlling properties on a diversity of immune cells. Increasingly, experimental sign suggests a character for IL-21 in the pathogenesis of numerous allergic disorders. The purpose of this review is to discuss the biological properties of IL-21 and to summaries current developments in its role in the regulation of allergic disorders.