World Allergy Organization Journal最新文献

Background: While epidemiological data suggest a connection between atopic dermatitis (AD) and COVID-19, the molecular mechanisms underlying this relationship remain unclear.

Objective: To investigate whether COVID-19-related CpGs may contribute to AD development and whether this association is mediated through the regulation of specific genes' expression.

Methods: We combined Mendelian randomization and transcriptome analysis for data-driven explorations.

Results: Among the 172 CpGs -associated with COVID-19 infection, merely 3 of them exhibited significant impacts on the risk of AD, including cg04543273, cg11916609, and cg10636246. In the following analysis of the causal effects of CpGs and their related gene expression, cg04543273 inhibited LMAN2 expression. However, there was not a significant impact of cg11916609 and cg10636246 on the expression of their corresponding genes. Besides, transcriptome analysis suggested that LMAN2 expression was significantly upregulated among the COVID-19-infected population, and LMAN2 expression was obviously correlated with Type 2 helper cells across different post-infection time points.

Conclusion: Overall, this study provides new insights of the COVID-19-related onset and exacerbation of AD-COVID-19-related epigenetic changes and their regulatory impact on transcription. A novel role of LMAN2 was proposed in the relationship between viral infection and AD. More studies are warranted to further explore the mechanism of LMAN2-related immunopathology.

Background: Many studies reported the influence of infants' gut microbiota on atopic dermatitis (AD) postnatally, yet the role of maternal gut microbiota and plasma metabolites in infants' AD remains largely unexplored.

Methods: Sixty-three pregnant mother-infants were enrolled and followed after childbirth in Guangzhou, China. Demographic information, maternal stool and plasma samples, and records for infants' AD were collected. Maternal gut microbiota/metabolome and plasma metabolome were profiled using shotgun metagenomics and non-targeted metabolomics. Logistic regression and multi-omics analysis were used to explore characteristic maternal gut microbiota in the AD and health groups.

Results: The α-diversity of maternal gut microbiota in health group was significantly higher than AD group (Shannon diversity P = 0.02, Simpson diversity P = 0.04). Short-chain fatty acids (SCFAs) producing microorganisms, including Faecalibacterium, Roseburia, Butyricicoccus, and Ruminococcus, as well as the abundance of phenylalanine, tyrosine, and tryptophan biosynthesis pathway, were enriched in health group (LDA>2 and P < 0.05). Virulent factors (VFs) involved in immune modulation were enriched in the health group, while VFs involving in adhesin were enriched in the AD group (P < 0.05). Metabolomic analysis showed that a polyunsaturated fatty acid/linoleic acid, 13S-hydroxyoctadecadienoic, were negatively associated with AD in both the gut and plasma samples (FDR<0.05). Several other linoleic acids and flavonoids were negatively associated with AD (FDR<0.05). Neural network analysis revealed that microorganisms enriched in health group may produce these protective fatty acids.

Conclusions: Our findings show that maternal gut microorganisms/metabolites and plasma metabolites during pregnancy impact subsequent pathogenesis of infants AD. This illuminates new strategies against early AD in offspring.

Background: While much of the evidence linking the rapid urbanization and the increasing prevalence of allergen sensitization, but little is known regarding rural-to-urban migrants. The aim of this study was to identify the disparities in allergy, the gut microbiome and factors among native urban, migrating, and native rural Chinese.

Methods: We redesigned the dataset of the China Alliance of Research on Respiratory Allergic Disease secondary survey, and after stratified sampling, a subsample of 2422 subjects were enrolled for the analysis of a questionnaire, skin prick tests (SPT), and specific immunoglobulin E (sIgE) titer measurements against 8 common allergens. Fecal microbiotal composition was also sequenced by 16S rRNA and regression-based analyses with covariate adjustment applied.

Results: From urban to migrant and rural populations, IgE sensitization was predominantly directed against Dermatophagoides pteronyssinus (Der p). The titers of Der p-sIgE decreased sequentially across the 3 respective populations and co-sensitization to other allergens also showed a sequential decrease. Rural-to-urban migrants showed a low prevalence of Der p-SPT and Der p-sIgE initially, but developed substantial IgE titers and their gut microbiotal diversity, as well as species richness, appeared to change along with residential time spent in the urban area. High-fat diet, using a mattress, an SPT wheal size from Der p ≥ 6 mm, and duration of immigration >5 years were significantly associated with sIgE positivity in the migrants.

Conclusion: The Der p-sIgE responses and the composition of gut microbiota differs synchronously with extended living time in an urban area. Studies in immigrants provide a unique opportunities to evaluate the effects of environmental factors in the pathogenesis of allergic disorders.

Background: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment.

Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR.

Results: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement.

Conclusions: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment.

Trial registration: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714).

Background: Allergen immunotherapy (AIT) is the only treatment that modifies the natural course of allergies. However, AIT is only used in some eligible patients, is frequently underused, and only a few studies investigated this aspects. Understanding AIT utilization patterns might disclose information about why it is underused, thus providing valuable insights on how to broaden the positive impact it can have on the population.

Methods: A questionnaire aiming to assess the trends of the use of AIT in Italy, patient health literacy on AIT, and the impact of respiratory allergies and AIT on patients' lives was submitted to patients affiliated with Respiriamo Insieme APS patient's association during the period between May and October 2023.

Results: Nine hundred forty-four patients completed the questionnaire. Most patients reported to be affected by allergic rhinitis (81.1%), allergic asthma (45.4%), and/or allergic conjunctivitis (41.2%), and many of them presenting a combination of these diseases. Only 53.8% knew about AIT's existence, and AIT was proposed to only 33.1% of the 858 patients affected by allergic rhinitis and/or allergic asthma, of which 29.2% decided not to initiate the therapy. Common reasons for AIT refusal were related to indecisiveness (26.5%), costs (22.9%), and skepticism (19.3%). Among the remaining 70.8% who accepted to start AIT, 21.4% discontinued the treatment beforehand, on average 18.26 months from initiation. There was a high heterogeneity in the suggested duration of AIT, with 20.4% of patients receiving indications to continue AIT for less than 3 years. AIT positively impacted patients' lives as most patients who completed AIT found it effective and safe, and experienced a significant reduction in the workdays/schooldays lost due to disease exacerbations.

Conclusions: The outcomes of this research pointed out a lot of misinformation surrounding AIT, calling for improvements in awareness and information on its efficacy and safety. Also, we noted a significant reduction in work/school days lost in patients who completed AIT and a good patient-reported safety and efficacy profile. We advocate for better economic accessibility through national-level standardization in treatment refundability. Notably, the collaboration with the patient association was crucial, and it would have been challenging to conduct this research otherwise.

Background: The incidence of anaphylaxis is increasing worldwide. However, there is a lack of data on anaphylaxis trends in Türkiye. This study aims to analyse trends in anaphylaxis-related emergency department (ED) visits and examines factors associated with fatal anaphylaxis in Türkiye.

Methods: We retrospectively analyzed data from Türkiye's Ministry of Health database from 2015 to 2022. Codes from the International Classification of Diseases, 10th revision (ICD-10), were used to identify anaphylaxis.

Results: During the study period, a total 21,370 ED admissions for anaphylaxis were identified, and anaphylaxis admissions increased 1.23-fold from 3.90 to 4.79 per 10⁵ population per year. The anaphylaxis trigger was unknown in 79.9% of cases, followed by drugs (11.7%), food (5.7%) and venom (2.7%). Epinephrine was administered in 49.6% of cases, and a total of 424 patients (2.1% of total cases) died. The frequency of intensive care unit (ICU) hospitalization increased 6.0-fold from 2015 to 2021, and age-adjusted average-weighted mortality rate for anaphylaxis was 0.66 per million. Older age, presence of asthma, and ICU hospitalization were found to be significantly associated with fatal anaphylaxis (p < 0.001 for all). Frequencies of death were 9.1% for venom anaphylaxis, 1.2% in drug anaphylaxis, and 0.2% for food anaphylaxis. Epinephrine autoinjector (EAI) was prescribed for 6.9% of all patients.

Conclusions: This is the first study of ED admissions for anaphylaxis using a large, nationwide data from Türkiye. Increasing numbers of ED admissions, ICU hospitalizations and mortality show that anaphylaxis is an important public health issue in Türkiye.

Background: Childhood rhinitis and asthma are allergic respiratory diseases triggered by common allergens, but they affect different parts of the respiratory system, leading to distinct symptoms. However, a comprehensive multi-biofluid metabolomics-based approach to uncover valuable insights into childhood allergies and allergen sensitization remains unaddressed.

Methods: Seventy-six children, comprising 26 with rhinitis, 26 with asthma, and 24 healthy controls, were enrolled. Fecal, blood, and urine metabolomic analyses using ¹H nuclear magnetic resonance (NMR) spectroscopy were conducted. An integrative analysis of their associations with allergen-specific IgE levels in the context of allergic rhinitis and asthma were also assessed.

Results: The analysis of 228 various biofluid samples revealed strong positive correlations between stool and blood metabolites, while blood metabolites exhibited negative correlations with most urine metabolites. Five and 19 metabolites were significantly different in children with rhinitis and asthma, respectively (P < 0.05). Among them, blood isovaleric acid correlated positively with stool IgE levels in rhinitis, while stool butyric acid and acetic acid in asthma exhibited strong negative correlations with total serum and mite allergen-specific IgE levels (P < 0.01). Blood metabolic profiles appeared to have the highest area under the curve (AUC) of 0.732 for rhinitis, whereas stool metabolic profiles had the highest AUC of 0.799 for asthma.

Conclusions: Multiple biofluid metabolomics provides comprehensive insights into childhood allergies, with blood profiles associated with allergic rhinitis and fecal profiles linked to asthma. Their short-chain fatty acid metabolites related to IgE levels emphasize the significant role of the gut microbiota in childhood rhinitis and asthma.

Background: Allergic rhinitis (AR) is a common chronic respiratory disease that can lead to the development of various other conditions. Although genetic risk loci associated with AR have been reported, the connections between these loci and AR comorbidities or other diseases remain unclear.

Methods: This study conducted a phenome-wide association study (PheWAS) using known AR risk loci to explore the impact of known AR risk variants on a broad spectrum of phenotypes. Subsequently, linkage disequilibrium score regression (LDSC) and bidirectional two-sample mendelian randomization (TSMR) analyses were used to further analyze the genetic correlation and causal relationships between significant and potentially related phenotypes and AR.

Results: The PheWAS analysis indicated significant associations between asthma, eczema, nasal polyps, hypothyroidism, and AR risk variants. Additionally, potential associations were observed with ulcerative colitis, psoriasis, chalazion, pernicious anemia, glaucoma, multiple sclerosis, arthritis, prostate cancer, varicose veins of lower extremities, and heart attack. LDSC analysis showed that only asthma, eczema, and nasal polyps have significant positive genetic correlations with AR. Furthermore, TSMR analysis revealed causal relationships between AR and asthma, eczema, and nasal polyps.

Conclusion: This study highlights the impact of AR risk loci on a variety of diseases. By revealing new associations and shared genetic pathways, our findings provide valuable insights into the pathophysiology of AR and pave the way for more effective targeted interventions to manage AR and its related diseases.

Background: Children allergic to milk and egg, but tolerant to baked products, display higher reactivity thresholds than the general population of children allergic to milk and egg. We sought to verify the reactivity thresholds of milk- and egg-allergic children who also react to baked milk and baked egg, respectively.

Methods: We retrospectively assessed consecutive oral food challenge (OFC) for baked milk and egg between January 2018 and March 2022 in a population of baked milk- and baked-egg allergic children.

Results: Among 407 children included (median age 56 - IQR 31.1-103.7 months, 67.1% male), 93 (23.6%) returned positive OFC results, 41 with baked milk, and 52 with baked egg. The most conservative ED01 was 0.4 mg total protein (IQR 0.1-2.7) for milk and 2.2 mg total protein (IQR 0.6-7.3) for egg. The respective ED05 was 3.9 (IQR 1.1-14) mg for milk and 11.7 (IQR 5-27.2) mg for egg. Such thresholds are consistent to those found for fresh milk (0.8 times for ED01, 1.1 times for ED05). For egg, they are 6.5 (egg ED01), and 7.5 (egg ED05) times lower than for native form.Compared to the currently used thresholds, they are 1.3 (milk ED01), 1.3 (milk ED05), 11 (egg ED01), and 4.9 (egg ED05) times higher.

Conclusions: Milk thresholds are similar to those already observed in baked allergic versus baked tolerant children, while EDs for egg are at least 1.6 times higher than those currently indicated.Egg-allergic patients could be exempt from the recommendations of absolute avoidance of foods when present in infinitesimal quantities, represented by precautionary allergen labelling based on current EDs.

Background: This study examined the relationship between the disciplinary diversity of research teams and research output (RO) in allergy and immunology programs funded by the National Institutes of Health (NIH) in the United States, Medical Research Council (MRC) in the United Kingdom, and Japan Society for the Promotion of Science (JSPS).

Methods: Using a dataset containing 1243, 3645, and 1468 articles funded by the NIH, MRC, and JSPS, respectively, we analyzed the correlation between disciplinary diversity and RO in allergy and immunology programs that received grants from 2017 to 2021. Diversity was measured using All Science Journal Classification codes counts, Shannon-Wiener index, and newly developed Omnidisciplinary index (o-index). The impact of diversity on RO was evaluated Normalized Paper Count (reflecting research quantity), Normalized Top 1% Paper Count (reflecting research excellence), and Normalized Top 10% Paper Count (reflecting research substantiality).

Results: There were no significant differences in diversity between the funding agencies, indicating a marginal relationship between team composition and RO (p = 0.641 for Shannon-Winner index). RO was positively correlated with team diversity in NIH- and MRC-funded programs and positively correlated with the degree of specialization in JSPS-funded programs.

Conclusions: These results underscore the complexity of the relationship between research team diversity and RO and the influence of contextual factors such as country-specific characteristics and grant program objectives. Specifically, the analysis of JSPS-funded groups suggests that the degree of specialization has a greater impact on RO than disciplinary diversity. This study contributes to ongoing efforts to optimize team composition to improve RO in allergy and immunology programs.