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1.
Front Pediatr ; 12: 1360420, 2024.
Article in English | MEDLINE | ID: mdl-38957776

ABSTRACT

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.

2.
Int Arch Allergy Immunol ; : 1-17, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952107

ABSTRACT

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.

3.
ACS Nano ; 18(26): 16934-16946, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38907988

ABSTRACT

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.


Subject(s)
Mast Cells , Mast Cells/drug effects , Mast Cells/metabolism , Mast Cells/immunology , Animals , Mice , Porosity , Silicon Dioxide/chemistry , Immunoglobulin E/immunology , Immunoglobulin E/metabolism , Mice, Inbred BALB C , Hypersensitivity/drug therapy , Hypersensitivity/immunology , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Passive Cutaneous Anaphylaxis/drug effects , Rhinitis, Allergic/drug therapy , Rhinitis, Allergic/immunology , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/pharmacology , Reactive Oxygen Species/metabolism , Humans , Particle Size
4.
Article in English | MEDLINE | ID: mdl-38908434

ABSTRACT

BACKGROUND: It is currently unclear whether cesarean section increases the risk of allergic diseases in offspring. OBJECTIVE: To investigate the association between cesarean section 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 to 1.25), allergic rhinitis/conjunctivitis (OR 1.15, CI 1.09 to 1.22), atopic dermatitis/eczema (OR 1.08, CI 1.04 to 1.13), food allergies (OR 1.35, CI 1.18 to 1.54), and allergic sensitization (OR 1.19, CI 1.10 to 1.28). Cesarean section 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 section rate accounted for some of the clinical heterogeneity. No data on allergic purpura were found. CONCLUSION: Most-adjusted estimates suggest that cesarean section is associated with increased risks of asthma, allergic rhinitis/conjunctivitis, atopic dermatitis/eczema, food allergies, and allergic sensitization in offspring. The impact of cesarean section on urticaria and purpura remains uncertain.

5.
J Leukoc Biol ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843075

ABSTRACT

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, remodelling, and the onset of allergic diseases. It has become increasingly clear that the process underlying immune and stromal cell activation during allergic sensitization require 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 last 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.

6.
Asia Pac Allergy ; 14(2): 63-69, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827257

ABSTRACT

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.

7.
Int Immunopharmacol ; 134: 111825, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38723368

ABSTRACT

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.


Subject(s)
Hypersensitivity , Interleukins , Humans , Interleukins/immunology , Interleukins/metabolism , Animals , Hypersensitivity/immunology , Th2 Cells/immunology , Mast Cells/immunology
8.
Heliyon ; 10(10): e30315, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38765036

ABSTRACT

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.

9.
Pediatr Allergy Immunol ; 35(5): e14147, 2024 May.
Article in English | MEDLINE | ID: mdl-38773751

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases. METHOD: We comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary-level data from genome-wide association studies. The analysis results mainly came from the random-effects model of inverse variance weighted (IVW-RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables. RESULTS: The IVW-RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01-1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01-1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00-1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01-1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = 2E-05), AAS (OR = 1.05, 95% CI = 1.02-1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00-1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98-1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis. CONCLUSION: This Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Hypersensitivity , Inflammatory Bowel Diseases , Mendelian Randomization Analysis , Humans , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/epidemiology , Hypersensitivity/genetics , Hypersensitivity/epidemiology , Polymorphism, Single Nucleotide , Asthma/genetics , Asthma/epidemiology , Crohn Disease/genetics , Crohn Disease/epidemiology , Dermatitis, Atopic/genetics , Dermatitis, Atopic/epidemiology , Colitis, Ulcerative/genetics , Colitis, Ulcerative/epidemiology , Risk Factors , Body Mass Index
10.
Arch Dermatol Res ; 316(5): 181, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762688

ABSTRACT

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.


Subject(s)
Arthritis, Psoriatic , Genome-Wide Association Study , Mendelian Randomization Analysis , Psoriasis , Humans , Mendelian Randomization Analysis/methods , Arthritis, Psoriatic/genetics , Arthritis, Psoriatic/epidemiology , Arthritis, Psoriatic/diagnosis , Psoriasis/genetics , Psoriasis/epidemiology , Psoriasis/immunology , Polymorphism, Single Nucleotide , Rhinitis, Allergic/genetics , Rhinitis, Allergic/epidemiology , Asthma/genetics , Asthma/epidemiology , Dermatitis, Atopic/genetics , Dermatitis, Atopic/epidemiology , Genetic Predisposition to Disease
11.
Biomedicines ; 12(5)2024 May 07.
Article in English | MEDLINE | ID: mdl-38790985

ABSTRACT

The synergic role of vitamin D and the intestinal microbiota in the regulation of the immune system has been thoroughly described in the literature. Vitamin D deficiency and intestinal dysbiosis have shown a pathogenetic role in the development of numerous immune-mediated and allergic diseases. The physiological processes underlying aging and sex have proven to be capable of having a negative influence both on vitamin D values and the biodiversity of the microbiome. This leads to a global increase in levels of systemic inflammatory markers, with potential implications for all immune-mediated diseases and allergic conditions. Our review aims to collect and analyze the relationship between vitamin D and the intestinal microbiome with the immune system and the diseases associated with it, emphasizing the effect mediated by sexual hormones and aging.

12.
Allergy ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38588176

ABSTRACT

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen-specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell-mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen-based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head-to-head comparative paediatric studies are scarce. Additionally, there are fewer placebo-controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well-designed studies.

13.
World Allergy Organ J ; 17(4): 100899, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38623319

ABSTRACT

Background: Several observational studies suggest a possible link between lipid-lowering drugs and allergic diseases. However, inferring causality from these studies can be challenging due to issues such as bias, reverse causation, and residual confounding. To investigate the potential causal effect of lipid-lowering drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitors, on allergic diseases (allergic asthma, allergic conjunctivitis, atopic dermatitis, allergic rhinitis, and allergic urticaria), we performed a Mendelian randomization (MR)-based study. Methods: We employed MR and summary-data-based MR (SMR), analyzing genome-wide association study (GWAS) data from people of European descent. Single nucleotide polymorphisms (SNPs) were employed as instrumental variables. We selected 2 types of genetic measures to represent the impact of lipid-lowering drugs, including genetic variants near or within drug target genes correlated with low-density lipoprotein cholesterol (LDL-C), and expression quantitative trait loci of drug target genes. The inverse-variance weighted (IVW)-MR approach was the primary utilized MR method, while sensitivity analyses were used to test the robustness of the results. We used SMR analysis as a supplementary analytical method, applying the heterogeneity in dependent instruments (HEIDI) test to assess if the observed correlation between gene expression and outcome was due to a linkage situation. Results: The IVW-MR analysis revealed significant evidence for an association between PCSK9-mediated LDL-C reduction and a decrease in the risk of allergic asthma (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.11-1.56; P < 0.01). Likewise, SMR analysis discovered an augmented expression of PCSK9 being linked with a heightened susceptibility to allergic asthma (OR = 1.21, 95% CI = 1.03-1.43; P = 0.02). No consistent evidence was found for other associations in either analysis. Conclusion: Our findings support a potential causal relationship between PCSK9 activity and an increased risk of allergic asthma. Thus, PCSK9 inhibitors, which reduce PCSK9 activity, might be considered a priority in future clinical trials investigating drugs for allergic asthma prevention or treatment.

14.
Front Immunol ; 15: 1364774, 2024.
Article in English | MEDLINE | ID: mdl-38629075

ABSTRACT

Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells.


Subject(s)
Asthma , Hypersensitivity , Natural Killer T-Cells , Humans , Hypersensitivity/therapy , Cytokines , Immunotherapy
15.
Cureus ; 16(3): e55912, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38601382

ABSTRACT

BACKGROUND: Constipation is a common gastrointestinal symptom in patients with ulcerative colitis (UC). Several studies on the general population have demonstrated a link between allergic diseases and constipation. However, evidence regarding the association between allergic diseases and constipation in UC is limited. This study aims to evaluate this issue in Japanese patients with UC. METHODS: This cross-sectional study recruited consecutive 387 patients with UC. We used a self-administered questionnaire to estimate the prevalence of physician-diagnosed allergic diseases. The definition of constipation was based on Rome I criteria and/or medication for constipation. RESULTS: The prevalence of constipation was 12.5%. The prevalence rates of asthma, atopic dermatitis, pollen allergy, food allergy, and drug allergy were 11.8%, 9.0%, 36.3%, 6.2%, and 8.3%, respectively. Allergic diseases were not associated with constipation (adjusted odds ratio [OR] with asthma (adjusted OR 0.98 [95% confidence interval [CI] 0.27-2.80]), atopic dermatitis (adjusted OR 0.67 [95% CI 0.10-2.56]), pollen allergy (adjusted OR 0.92 [95% CI 0.41-1.97]), food allergy (adjusted OR 0.76 [95% CI 0.11-2.95]), and drug allergy (adjusted OR 1.06 [95% CI 0.28-3.24]). Additionally, the number of allergic diseases was not associated with the prevalence of constipation. CONCLUSIONS: In Japanese UC patients, no association between allergic diseases and constipation was found.

16.
Clin Transl Allergy ; 14(4): e12350, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38573314

ABSTRACT

BACKGROUND: Allergic diseases typically refer to a heterogeneous group of conditions primarily caused by the activation of mast cells or eosinophils, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma. Asthma, AR, and AD collectively affect approximately one-fifth of the global population, imposing a significant economic burden on society. Despite the availability of drugs to treat allergic diseases, they have been shown to be insufficient in controlling relapses and halting disease progression. Therefore, new drug targets are needed to prevent the onset of allergic diseases. METHOD: We employed a Mendelian randomization approach to identify potential drug targets for the treatment of allergic diseases. Leveraging 1798 genetic instruments for 1537 plasma proteins from the latest reported Genome-Wide Association Studies (GWAS), we analyzed the GWAS summary statistics of Ferreira MA et al. (nCase = 180,129, nControl = 180,709) using the Mendelian randomization method. Furthermore, we validated our findings in the GWAS data from the FinnGen and UK Biobank cohorts. Subsequently, we conducted sensitivity tests through reverse causal analysis, Bayesian colocalization analysis, and phenotype scanning. Additionally, we performed protein-protein interaction analysis to determine the interaction between causal proteins. Finally, based on the potential protein targets, we conducted molecular docking to identify potential drugs for the treatment of allergic diseases. RESULTS: At Bonferroni significance (p < 3.25 × 10-5), the Mendelian randomization analysis revealed 11 significantly associated protein-allergic disease pairs. Among these, the increased levels of TNFAIP3, ERBB3, TLR1, and IL1RL2 proteins were associated with a reduced risk of allergic diseases, with corresponding odds ratios of 0.82 (0.76-0.88), 0.74 (0.66-0.82), 0.49 (0.45-0.55), and 0.81 (0.75-0.87), respectively. Conversely, increased levels of IL6R, IL1R1, ITPKA, IL1RL1, KYNU, LAYN, and LRP11 proteins were linked to an elevated risk of allergic diseases, with corresponding odds ratios of 1.04 (1.03-1.05), 1.25 (1.18-1.34), 1.48 (1.25-1.75), 1.14 (1.11-1.18), 1.09 (1.05-1.12), 1.96 (1.56-2.47), and 1.05 (1.03-1.07), respectively. Bayesian colocalization analysis suggested that LAYN (coloc.abf-PPH4 = 0.819) and TNFAIP3 (coloc.abf-PPH4 = 0.930) share the same variant associated with allergic diseases. CONCLUSIONS: Our study demonstrates a causal association between the expression levels of TNFAIP3 and LAYN and the risk of allergic diseases, suggesting them as potential drug targets for these conditions, warranting further clinical investigation.

17.
Clin Rev Allergy Immunol ; 66(2): 149-163, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38639856

ABSTRACT

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 (PM1, PM2.5, PM10, NO, NO2, SO2, CO, and O3) 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 PM2.5 and NO2 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/m3 increase, respectively. Maternal exposure to PM1, PM2.5, and NO2 with a 10 µg/m3 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 PM2.5 and NO2 with a 10 µg/m3 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 PM2.5 and NO2, 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.


Subject(s)
Air Pollutants , Hypersensitivity , Maternal Exposure , Prenatal Exposure Delayed Effects , Humans , Pregnancy , Female , Prenatal Exposure Delayed Effects/epidemiology , Air Pollutants/adverse effects , Child , Maternal Exposure/adverse effects , Hypersensitivity/etiology , Hypersensitivity/epidemiology , Air Pollution/adverse effects , Particulate Matter/adverse effects , Child, Preschool
18.
Front Pharmacol ; 15: 1322788, 2024.
Article in English | MEDLINE | ID: mdl-38549675

ABSTRACT

Aims: Cetirizine is frequently administered at an increased dosage in clinical practice and recommended by several guidelines. Nonetheless, the pharmacokinetic (PK) profile and real-world safety data remain insufficient in the Chinese pediatric population. The objective of the current study is to develop a population pharmacokinetic (PPK) model for cetirizine in Chinese pediatric patients and to investigate the rationale behind its off-label usage. Methods: A prospective cohort study was conducted, enrolling children who had been diagnosed with allergic diseases and prescribed cetirizine. The outcomes were safety and pharmacokinetic (PK) parameters. Cetirizine concentrations were measured using a pre-established analytical method. Subsequently, a PK model was developed, followed by model evaluation and simulation. The developed PK model was employed to investigate the drug exposure differences across various age groups and to simulate scenarios of potential overdose. Results: Sixty-three children were enrolled, and 24 of them received a cetirizine dose exceeding the recommended dosage. A PPK model, based on published literature, served as the basis of our analysis, with adjustment made to estimate certain parameters. The final model evaluation and validation indicated accurate predictive performance and robust parameter estimation. Simulations conducted for the label-dose among age 1-12 indicated median maximum concentration at steady state (Cmax,ss) of 7 year old children could be the highest. The model was also used to predict the off-label dose scenarios and overdose patient to support the clinical decision. There were no adverse drug reactions in either group. Conclusion: This study provides evidence-based and model-based exploration for optimizing cetirizine usage in Chinese pediatric patients. The cetirizine PPK model showed accurate predictive performance and could be utilized to simulate individual patient exposure in real-world clinical scenarios.

19.
Front Med (Lausanne) ; 11: 1347152, 2024.
Article in English | MEDLINE | ID: mdl-38533318

ABSTRACT

Background: Evidence from observational studies and clinical trials suggests that the allergic diseases (ADs) are associated with kidney diseases (KDs). However, the causal association between them remains to be determined. We used bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the potential causality between them. Methods: Mendelian randomization (MR) was performed using publicly available genome-wide association study (GWAS) summary datasets. Inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods are used to evaluate the causality between ADs and KDs. Sensitivity and heterogeneity analyses were used to ensure the stability of the results. Results: The MR results indicated that genetic susceptibility to ADs was associated with a higher risk of CKD [odds ratio (OR) = 1.124, 95% CI = 1.020-1.239, p = 0.019] and unspecified kidney failure (OR = 1.170, 95% CI = 1.004-1.363, p = 0.045) but not with kidney stone, ureter stone or bladder stone (OR = 1.001, 95% CI = 1.000-1.002, p = 0.216), other renal or kidney problem (OR = 1.000, 95% CI = 1.000-1.001, p = 0.339), urinary tract or kidney infection (OR = 1.000, 95% CI = 0.999-1.001, p = 0.604), kidney volume (OR = 0.996, 95% CI = 0.960-1.033, p = 0.812) and cyst of kidney (OR = 0.914, 95% CI = 0.756-1.105, p = 0.354). No causal evidence of KDs on ADs was found in present study. Conclusion: Results from MR analysis indicate a causal association between ADs and CKD and unspecified kidney failure. These findings partly suggest that early monitoring of CKD risk in patients with ADs is intentional.

20.
Res Rep Trop Med ; 15: 25-49, 2024.
Article in English | MEDLINE | ID: mdl-38406662

ABSTRACT

Background: Helicobacter pylori (H. pylori) is believed to have spread from East Africa, but its burden is still unknown in less privileged regions of Ethiopia. Indigestion is an upset stomach, upper abdomen discomfort, heartburn, and bloating. This study evaluated the burden and risk factors for H. pylori infection among government employees who clinically complained of indigestion but allergic diseases in five public health institutions in Southeastern Ethiopia. Methods: A health facilities-based cross-sectional survey study was conducted in Southeastern Ethiopia from March to November 2022, employing cluster sampling. Blood specimens, clinical data, and semi-structured questionnaires about risk factors were collected. Data analysis was conducted using descriptive, bivariate, and multivariable logistic regression in STATA software, Windows version 16.1. Results: The overall prevalence of infection was found to be 77.6%. The sampled health institution (ρ-value < 0.05), engagement in sideline business (ρ-value < 0.05), sharing local spoon on meal [AOR = 39.30; CI:19.52 -78.31; ρ-value < 0.001], admitting "Gursha" during meal [AOR = 71.48; CI:3.99 -1279.77; ρ-value < 0.05], the toilet type [AOR = 1410.98; CI:121.16 -16,431.19; ρ-value < 0.001], alcohol drinking [AOR = 15.15; CI:1.90 -120.62; ρ-value < 0.05], sleeping hours length [AOR = 15.01; CI:13.48-55.96; ρ-value < 0.001], chewing Khat [AOR = 76.73; CI:8.57-687.07; ρ-value < 0.001], and regular hand washing before eating [AOR = 0.15; CI:0.12-0.19; ρ-value < 0.05] were the independent predictors of H. pylori infection. Conclusion: The prevalence rate of H. pylori infection in Southeastern Ethiopia is agonizingly high, exceeding the world average by 27.6%, the first report, and seems to be one of the neglected infectious diseases. Hence, the Oromia Region Health Bureau should reinvigorate the basic infectious disease control methods, establish routine laboratory diagnostic platforms, and intervene in selected societal practices spreading infections.

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