World Allergy Organization Journal最新文献

{"title":"Exploring cytokine outputs for ex vivo diagnostics in drug reaction with eosinophilia and systemic symptoms (DRESS)","authors":"Ana M. Copaescu MD, FRCPC ,&nbsp;Effie Mouhtouris BSc ,&nbsp;Fiona James BBiomedSci ,&nbsp;Michelle S.Y. Goh MBBS, FACD ,&nbsp;Elizabeth J. Phillips MD, FRCPC, FRACP ,&nbsp;Jason A. Trubiano MBBS, BBiomedSci, FRACP, PhD ,&nbsp;for Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)","doi":"10.1016/j.waojou.2024.101002","DOIUrl":"10.1016/j.waojou.2024.101002","url":null,"abstract":"<div><h3>Background</h3><div>In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.</div></div><div><h3>Methods</h3><div>Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs. As comparative controls, these cytokine outputs were performed simultaneously in patients with a positive <em>ex vivo</em> IFN-γ release ELISpot result.</div></div><div><h3>Results</h3><div>Four antibiotic-associated DRESS cases were included. The IL-4 and IL-5 output ELISpot assay demonstrated various results among these patients, with at least 1 cytokine present in all the cases. As for the 2 controls with known positive IFN-γ release, compared to the IFN-γ secretion, the cytokine output using IL-4 and IL-5 showed an increased positivity.</div></div><div><h3>Conclusion</h3><div>In patients where the early response has suggested a TH2 response such as DRESS, IL-4 and IL-5 cytokine outputs could present an investigational advantage, including when IFN-γ is negative. In the future, larger prospective studies are required to understand the role of varied cytokine outputs in T-cell-mediated hypersensitivities.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101002"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-omics Mendelian randomization identifies putatively causal genes and DNA methylation sites for asthma","authors":"Jia Wang MD ,&nbsp;Jinxin Hu MS ,&nbsp;Dan Qin MD ,&nbsp;Dan Han MD ,&nbsp;Jiapeng Hu MD","doi":"10.1016/j.waojou.2024.101008","DOIUrl":"10.1016/j.waojou.2024.101008","url":null,"abstract":"<div><h3>Background</h3><div>Asthma is a global chronic respiratory disease with complex pathogenesis. While current therapies offer some relief, they often fall short in effectively managing symptoms and preventing exacerbations for numerous patients. Thus, understanding its mechanisms and discovering new drug targets remains a pressing need for better treatment.</div></div><div><h3>Methods</h3><div>Using the GEO dataset, we screened differentially expressed genes (DEGs) in asthma patients' blood. Employing Summary Data-based Mendelian Randomization (SMR) and Two-Sample Mendelian Randomization (TSMR), we pinpointed asthma causal genes, causal DNA methylation sites, and methylation sites affecting gene expression, cross validated with at least 2 large-scale GWAS from each source. We utilized colocalization for genetic associations, meta-analysis for data integration, two-step MR for methylation-gene-asthma mediation mechanism. Druggability was evaluated using Open Target, virtual screening, and docking.</div></div><div><h3>Results</h3><div>Among the 954 DEGs found in asthma patients' blood, increased expression of CEP95 (discovery, OR_SMR = 0.94, 95% CI: 0.91–0.97), RBM6 (discovery, OR_SMR = 0.97, 95% CI: 0.95–0.99), and ITPKB (discovery, OR_SMR = 0.82, 95% CI: 0.74–0.92) in the blood decreased the risk of asthma, higher levels of HOXB-AS1 (discovery, OR_SMR = 1.05, 95% CI: 1.03–1.07), ETS1 (discovery, OR_SMR = 1.62, 95% CI: 1.29–2.04), and JAK2 (discovery, OR_SMR = 1.13, 95% CI: 1.06–1.21) in the blood increased the risk of asthma. Additionally, a total of 8 methylation sites on ITPKB, ETS1, and JAK2 were identified to influence asthma. An increase in methylation at site cg16265553 raised the risk of asthma partially by suppressing ITPKB expression. Similarly, increased methylation at cg13661497 reduced the asthma risk totally by suppressing JAK2 expression. The impact of CEP95, HOXB-AS1, and RBM6 expressions on asthma was further confirmed in lung tissues. Except for HOXB-AS1, all the other genes were potential druggable targets.</div></div><div><h3>Conclusion</h3><div>Our study highlighted that specific gene expressions and methylation sites significantly influence asthma risk and revealed a potential methylation-to-gene-to-asthma mechanism. This provided pivotal evidence for future targeted functional studies and the development of preventive and treatment strategies.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101008"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management and disease burden of children and adults with severe IgE-mediated food allergy: Are adults the lost population?","authors":"Katharina Blumchen MD ,&nbsp;Martin Hutter MSc ,&nbsp;Sabine Schnadt MSc ,&nbsp;Gregor Bushart PhD ,&nbsp;Claudia Mailaender PhD","doi":"10.1016/j.waojou.2024.100971","DOIUrl":"10.1016/j.waojou.2024.100971","url":null,"abstract":"<div><h3>Background</h3><div>Lacking causal treatment options in most cases, severe IgE-mediated food allergies (IgE-FA) are associated with a high burden of disease due to permanent risk of anaphylactic reactions after accidental allergen ingestion. To date, only few data comparing health resources and burden of disease between the pediatric and adult population are available.</div></div><div><h3>Objective</h3><div>Our survey aimed to assess the care situation of pediatric and adult patients with severe, self-reported physician-diagnosed IgE-FA.</div></div><div><h3>Methods</h3><div>The survey was conducted via an online questionnaire consisting of 32 items covering participant demographics, comorbidities, triggers, utilization of health resources, current management and burden of disease of FA, according to age groups (&lt;18 years: proxy report by parents or ≥ 18 years: self-report by adults).</div></div><div><h3>Results</h3><div>A total of 367 participants (n = 237 children/parents, n = 130 adults) with self-reported physician-diagnosed IgE-FA and physician-prescribed adrenalin autoinjector were enrolled. Emergency training and having an emergency action plan were significantly more common in the pediatric group (81.4%) than in the adult group (36.2%). Children had clearer medical contact points (pediatrician or [pediatric] pulmonologist, 89.0%), while adults visited a variety of specialized physicians according to their FA-related symptoms. Adults were more unsatisfied with their overall coping-strategy for allergen avoidance (18.5%), daily FA management (27.9%), and treating physician (34.4%) than the pediatric group (2.6%/17.0%/14.8%, respectively, p &lt; 0.05).</div></div><div><h3>Discussion</h3><div>Our data reveal a general undersupply for severe IgE-FA in Germany, with adults being significantly more affected. This may lead to the reported higher burden of disease in this age group. Increasing clearer medical contact points (eg, qualified allergologists specialized in food allergy)—especially for the adult patient population, finding available therapeutic options for this group of patients, and increasing the awareness of severe food allergy in the general population might overcome this problem.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100971"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social inequalities in childhood asthma","authors":"Angela Pinot de Moira PhD,&nbsp;Adnan Custovic MD, PhD, FMedSci","doi":"10.1016/j.waojou.2024.101010","DOIUrl":"10.1016/j.waojou.2024.101010","url":null,"abstract":"<div><div>Asthma is a complex, heterogeneous condition, broadly characterized by chronic airway inflammation with variable expiratory airflow limitation, but with several subtypes underpinned by different (although likely overlapping) pathological mechanisms. It is one of the most common chronic diseases of childhood and represents a significant cost for healthcare systems and affected families. Evidence suggests that a disproportionate proportion of this burden falls on families from disadvantaged socioeconomic circumstances (SECs).</div><div>In this review, we describe the extent to which growing up in disadvantaged SECs is associated with an increased risk of childhood asthma diagnosis and asthma outcomes, including how this differs geographically and across different asthma subtypes. We also discuss the complex and interdependent mediating pathways that may link disadvantaged SECs with childhood asthma and asthma-related outcomes.</div><div>In high-income countries (HICs), there is a fairly consistent association between growing up in disadvantaged SECs and increased prevalence of childhood asthma. However, evidence suggests that this social patterning differs across different asthma subtypes, with asthma phenotypes associated with disadvantaged SECs being less likely to be associated with atopy and more likely to begin in infancy and persist into adolescence. Disadvantaged SECs are also associated with worse asthma outcomes, which may contribute to the persistence of symptoms among disadvantaged children.</div><div>In low- and middle-income countries (LMICs), the patterns are more variable and data more limited, but there is some evidence that disadvantaged SECs and atopic asthma are similarly negatively associated. There are also clear disparities in asthma outcomes, with LMICs having disproportionately high asthma-related morbidity and mortality, despite having lower asthma prevalence. A lack of accessibility to essential medication and appropriate care no doubt contributes to these disparities.</div><div>The pathways leading to social inequalities in asthma are complex and interdependent, and as yet not fully understood. There is a clear need for further research into the relative importance of potential mediating pathways, including how these vary across the life course and across asthma subtypes. A stronger understanding of these pathways will help identify the most effective policy entry points for intervention, ultimately reducing inequalities across the life course.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101010"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fel d 1 specific IgE measurement for dog exclusive owners co-sensitized to dog and cat","authors":"Lin Liang MD ,&nbsp;Ah-Reum Hwang MS ,&nbsp;Yoon Ji Shin BS ,&nbsp;Kyoung Yong Jeong PhD ,&nbsp;Kyung Hee Park MD, PhD ,&nbsp;Jae-Hyun Lee MD, PhD ,&nbsp;Jung-Won Park MD, PhD","doi":"10.1016/j.waojou.2024.101007","DOIUrl":"10.1016/j.waojou.2024.101007","url":null,"abstract":"<div><h3>Background</h3><div>The diagnosis of the culprit allergen depends on exposure, symptoms at exposure, and the presence of specific IgE (sIgE). Pet allergens are sticky and can sensitize individuals without adoption history. Exclusive dog owners frequently exhibit both dog (e5) and cat dander sIgE (e1). We assessed whether the measurement of Fel d 1 sIgE (e94) can discriminate true cat sensitization from false positivity by cross-reactivity in the exclusive dog owners.</div></div><div><h3>Methods</h3><div>Thirty-one patients with respiratory allergies who exclusively owned dogs were enrolled for this study. e5, e1, and e94 were measured with ImmunoCAP. ELISA inhibition was performed to assess cross-reactivity.</div></div><div><h3>Results</h3><div>About 81% of patients (25/31) were both e5 and e1 positive, and 8 were also positive for e94. In the e94 positive, cat dander exhibited higher maximum inhibition of cat sIgE (94% vs 88%) and demonstrated lower IC₅₀ (6.5 vs 737.9 BAU/mL) compared to dog dander. Conversely, in the e94 negative, dog dander demonstrated higher maximum inhibition of cat dander sIgE (71.9% vs 56.2%) and lower IC₅₀ (172 vs 1947 BAU/mL) compared to cat dander. In the e94 positive, dog dander exhibited higher maximal inhibition for dog sIgE (91.5 vs 76.1%) and lower IC₅₀ (10.6 vs 1679 BAU/mL) compared to cat dander, whereas in the e94 negative, the IC₅₀ for cat dander could not be determined.</div></div><div><h3>Conclusions</h3><div>Genuine co-sensitization to cats is notable even in individuals who exclusively own dogs. Positive e94 results could discriminate authentic cat sensitization from false positivity by cross-reactivity in these patients, underscoring the importance of comprehensive allergy assessment.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101007"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perceptions of the impact of individual allergic rhinitis symptoms: A survey of ARIA clinical experts","authors":"Sara Gil-Mata MD ,&nbsp;Tatiana Teixeira MD ,&nbsp;Anna Bedbrook BSc ,&nbsp;Jean Bousquet PhD ,&nbsp;Bernardo Sousa-Pinto PhD ,&nbsp;Rafael José Vieira MD","doi":"10.1016/j.waojou.2024.100999","DOIUrl":"10.1016/j.waojou.2024.100999","url":null,"abstract":"<div><h3>Background</h3><div>Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients.</div></div><div><h3>Methods</h3><div>We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms.</div></div><div><h3>Results</h3><div>Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients.</div></div><div><h3>Conclusion</h3><div>Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100999"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allergic disease and keratoconus: A two-sample univariable and multivariable Mendelian randomization study","authors":"Hanlu Xu ,&nbsp;Yajing Wen ,&nbsp;Huikang Zheng ,&nbsp;Dan Jiang ,&nbsp;Wei Chen","doi":"10.1016/j.waojou.2024.100993","DOIUrl":"10.1016/j.waojou.2024.100993","url":null,"abstract":"<div><h3>Background</h3><div>There is accumulating evidence that allergy is a risk factor for keratoconus. Nonetheless the association between allergic disease and keratoconus remains controversial. We performed a two-sample Mendelian randomization (MR) study to determine the putative causal association of 4 allergic diseases (allergic conjunctivitis, allergic asthma, allergic rhinitis and atopic dermatitis) with keratoconus.</div></div><div><h3>Methods</h3><div>Summary statistics were obtained from genome-wide association studies (GWAS) of allergic conjunctivitis (AC) (20,958 cases and 356,319 controls), allergic asthma (AA) (9631 cases and 210,122 controls), allergic rhinitis (AR) (11,009 cases and 359,149 controls), atopic dermatitis (AD) (13,473 cases and 336,589 controls), keratoconus (KC) (2116 cases and 24,626 controls) and 91 circulating inflammatory cytokines (n = 14,824). Two-sample univariable and multivariable MR analyses were performed. A two-step MR was then applied to determine whether systemic inflammatory cytokines mediated the effect of allergic disease on keratoconus.</div></div><div><h3>Results</h3><div>The causal odds ratio (OR) estimate of genetically determined KC was 1.66 (95% CI: 1.32–2.08; P &lt; 0.001) for AC, 1.29 (95% CI: 1.10–1.51, P = 0.0014) for AA, 1.39 (95% CI: 1.15–1.68; P &lt; 0.001) for AR and 1.30 (95% CI: 1.17–1.45, P &lt; 0.001) for AD. Multivariable MR indicated a suggestive association between AC and KC after conditioning on other allergic diseases (OR 1.61; 95% CI: 1.10–2.34; P adjusted = 0.054). Two-step MR revealed that the effect was not mediated by systemic inflammatory cytokines.</div></div><div><h3>Conclusions</h3><div>Our findings provide evidence of a potential causal relationship between AC and KC. The effect of AC on KC may be mediated via other systemic inflammatory cytokines not included in the present study, or by alternative mechanisms. These findings may offer insight for prevention and intervention strategies to lower the risk of KC in patients with AC.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100993"},"PeriodicalIF":3.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing pharmacists versus allergists in low-risk penicillin allergy delabelling: The Hong Kong Penicillin Allergy Pharmacist Initiative (HK-PAPI)","authors":"James K.Y. Hooi MBChB ,&nbsp;Marshall C.H. Low BPharm ,&nbsp;Jonathan C.L. To BPharm ,&nbsp;Hugo W.F. Mak MBBS ,&nbsp;Mandy M. Choi BPharm ,&nbsp;Chris C.P. Tam BPharm ,&nbsp;Raymond W.M. Mak MSc ,&nbsp;Vincent K.C. Wong MPharm ,&nbsp;Timo C.C. Chan MClinPharm ,&nbsp;Andrew W.T. Li MClinPharm ,&nbsp;Charlie C.Y. Mak MClinPharm ,&nbsp;Valerie Chiang MBBS ,&nbsp;Gordon K.H. Chu MBBS ,&nbsp;Jane C.Y. Wong MBBS ,&nbsp;Philip H. Li MD","doi":"10.1016/j.waojou.2024.101003","DOIUrl":"10.1016/j.waojou.2024.101003","url":null,"abstract":"<div><h3>Background</h3><div>Mislabelled penicillin allergies are associated with a myriad of adverse outcomes and development of anti-microbial resistance. With the overwhelming need for specialist allergy services, pharmacist initiatives such as the Hong Kong Penicillin Allergy Pharmacist Initiative (HK-PAPI) have been advocated. However, evidence of their effectiveness, safety and impact on health-related quality-of-life (HR-QoL) are lacking.</div><div>To assess and compare the effectiveness, safety and improvements on HR-QoL of pharmacists vs allergists in a pilot low-risk penicillin allergy delabelling initiative.</div></div><div><h3>Methods</h3><div>All adult patients referred for low-risk penicillin allergy were randomized and evaluated by either pharmacists or allergists in a 1:3 ratio. Outcomes and changes in Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) scores were compared.</div></div><div><h3>Results</h3><div>Of 323 patients referred, 96.3% (311/323) completed penicillin allergy evaluation (pharmacists: 83 [24.3%] vs allergists: 228 [66.7%]). Overall, 93.6% (291/311) were delabelled with no difference between evaluations by pharmacists and allergists (92.8% vs 93.9%, p = 0.729). There were no severe or systemic reactions in either cohort. Patients evaluated by either pharmacists (43.4 [SD:29.1] to 10.5 [SD:5.93], p &lt; 0.001) or allergists (37.2 [SD:22.2] to 29.1 [SD:22.4], p &lt; 0.001) reported improved HR-QoL as reflected by DrHy-Q scores. However, absolute changes in DrHy-Q scores were significantly greater among patients evaluated by pharmacists compared to those by allergists (−24.6 [SD:25.1] vs −9.19 [SD:13.7], p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Evaluations and delabelling by pharmacists (vs allergists) were comparably effective and safe among patients with low-risk penicillin allergy. Moreover, patients evaluated by pharmacists even reported significantly greater improvements in HR-QoL, highlighting the potential of multidisciplinary allergy initiatives.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 101003"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levels of total IgE versus specific IgE during childhood for defining and predicting T2-high asthma","authors":"Tamo Sultan MD ,&nbsp;Frederikke Skov MD ,&nbsp;Nicklas Brustad MD, PhD ,&nbsp;Nilo Vahman MD, PhD ,&nbsp;Jakob Stokholm MD, PhD ,&nbsp;Klaus Bønnelykke MD, PhD ,&nbsp;Ann-Marie Malby Schoos MD, PhD, DMSc ,&nbsp;Bo Chawes MD, PhD, DMSc","doi":"10.1016/j.waojou.2024.100994","DOIUrl":"10.1016/j.waojou.2024.100994","url":null,"abstract":"<div><h3>Background</h3><div>T2-high asthma is characterized by elevated blood eosinophils (b-eos), and/or fractional exhaled nitric oxide (FeNO), and/or being “allergy-driven”, which is not well-defined.</div></div><div><h3>Objective</h3><div>To investigate the role of total and specific immunoglobulin E (tIgE/sIgE) for defining and predicting T2-high asthma in childhood as biomarkers of “allergy-driven”.</div></div><div><h3>Methods</h3><div>We utilized data from the COPSAC2000 (n = 411) and COPSAC2010 (n = 700) mother-child cohorts with repeated measurements of tIgE, sIgE, b-eos and FeNO through childhood. We defined T2-high asthma by elevated b-eos (≥0.3 × 10⁹/L) and/or FeNO (≥20 ppb) and analyzed association with elevated tIgE (age-specific cut-offs) and sIgE (≥0.35 kU/L) using logistic regression at ages 7/10/13/18 years. Further, we analyzed the association between elevated tIgE and sIgE at age 0–4 years and later risk of T2-high asthma using logistic regression and ROC models.</div></div><div><h3>Results</h3><div>Elevated tIgE was associated with risk of T2-high asthma at all time points, whereas elevated sIgE showed similar results at ages 10/13/18 years. There was no overall model fit preference for a combination of tIgE and sIgE instead of tIgE or sIgE alone using Vuong's Likelihood-Ratio-Test, Akaike or Bayesian Information Criterion. Further, elevated tIgE at age 0–4 years was associated with later risk of T2-high asthma at all time points (AUC = 0.63–0.70, sensitivity = 0.62–0.81, specificity = 0.57–0.78), whereas elevated sIgE at 0–4 years was only associated with T2-high asthma at 18 years (AUC = 0.66, sensitivity = 0.45, specificity = 0.88). There were no significant differences in AUC values between tIgE and sIgE (DeLong's test).</div></div><div><h3>Conclusion</h3><div>Elevated tIgE and sIgE are equally useful stand-alone biomarkers for defining and predicting risk of T2-high asthma in childhood.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100994"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the pathogenic effects of smoking in blood DNA methylation on allergic diseases","authors":"Junhao Tu PhD, MD ,&nbsp;Wei Wan PhD, MD ,&nbsp;Binxiang Tang MSc ,&nbsp;Fan Jiang MSc ,&nbsp;Jinyang Wen PhD, MD ,&nbsp;Qing Luo PhD, MD ,&nbsp;Jing Ye PhD, MD","doi":"10.1016/j.waojou.2024.100995","DOIUrl":"10.1016/j.waojou.2024.100995","url":null,"abstract":"<div><h3>Background</h3><div>Allergic diseases, such as asthma and allergic rhinitis, present significant health challenges globally. Elucidating the genetic and epigenetic foundations is crucial for developing effective interventions.</div></div><div><h3>Methods</h3><div>We performed two-sample Mendelian Randomization (MR) analyses to investigate the associations between smoking behaviors and various allergic diseases, leveraging data from the FinnGen database. Additionally, we examined the relationships of DNA methylation (CpG sites) with allergic diseases, employing mQTLs as epigenetic proxies. Furthermore, we conducted reverse MR analyses on CpG sites that exhibited cross-allergic disease effects.</div></div><div><h3>Results</h3><div>In our genomic MR analysis, smoking behaviors such as smoking initiation and the number of cigarettes smoked per day were identified to be causally associated with an increased risk of asthma. Additionally, there was suggestive evidence linking smoking initiation to atopic contact dermatitis. Our epigenetic MR analysis found that methylation changes at 46 CpG sites, assessed via mQTLs, were significantly associated with asthma risk. Notably, cg17272563 (PRRT1), cg03689048 (BAT3), cg20069688 (STK19), and cg20513976 (LIME1) were identified with cross-allergic effects. Crucially, reverse MR analysis substantiated these associations.</div></div><div><h3>Conclusions</h3><div>Our study has highlighted the associations between smoking behaviors and allergic diseases in the genetic and epigenetic landscape, notably asthma. We identified several DNA methylation-related CpG sites, such as cg03689048 (BAT3), cg17272563 (PRRT1), and cg20069688 (STK19), which demonstrate cross-allergic potential and reverse causal relationships.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":"17 12","pages":"Article 100995"},"PeriodicalIF":3.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}