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Exploring cytokine outputs for ex vivo diagnostics in drug reaction with eosinophilia and systemic symptoms (DRESS) 探索细胞因子输出用于体外诊断与嗜酸性粒细胞增多和全身症状(DRESS)的药物反应。
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-12-01 DOI: 10.1016/j.waojou.2024.101002
Ana M. Copaescu MD, FRCPC , Effie Mouhtouris BSc , Fiona James BBiomedSci , Michelle S.Y. Goh MBBS, FACD , Elizabeth J. Phillips MD, FRCPC, FRACP , Jason A. Trubiano MBBS, BBiomedSci, FRACP, PhD , for Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)

Background

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.

Methods

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 ex vivo IFN-γ release ELISpot result.

Results

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.

Conclusion

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.
背景:在一项评估抗生素相关的严重t细胞介导的超敏反应个体化t细胞诊断潜力的探索性研究中,我们重点研究了嗜酸性粒细胞和全身症状(DRESS)的药物反应以及相关的细胞因子输出IL-4和IL-5。方法:前瞻性招募表型良好的RegiSCAR≥4 DRESS、皮内皮肤试验阳性、先前IFN-γ酶联免疫斑点(ELISpot)试验阴性的患者。我们专门对IL-4和IL-5细胞因子输出进行了ELISpot检测。作为对照,这些细胞因子输出在体外IFN-γ释放阳性ELISpot结果的患者中同时进行。结果:纳入4例抗生素相关DRESS病例。IL-4和IL-5输出ELISpot检测在这些患者中显示出不同的结果,所有病例中至少存在1种细胞因子。对于已知IFN-γ释放阳性的2个对照组,与IFN-γ分泌相比,使用IL-4和IL-5的细胞因子输出呈阳性增加。结论:在早期反应表明TH2反应如DRESS的患者中,IL-4和IL-5细胞因子输出可能呈现研究优势,包括当IFN-γ为阴性时。在未来,需要更大规模的前瞻性研究来了解不同细胞因子输出在t细胞介导的超敏反应中的作用。
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引用次数: 0
A multi-omics Mendelian randomization identifies putatively causal genes and DNA methylation sites for asthma 多组学孟德尔随机化鉴定哮喘的推定因果基因和DNA甲基化位点。
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-12-01 DOI: 10.1016/j.waojou.2024.101008
Jia Wang MD , Jinxin Hu MS , Dan Qin MD , Dan Han MD , Jiapeng Hu MD

Background

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.

Methods

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.

Results

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.

Conclusion

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.
背景:哮喘是一种全球性的慢性呼吸系统疾病,发病机制复杂。虽然目前的治疗方法提供了一些缓解,但它们往往不能有效地控制症状和防止许多患者的病情恶化。因此,了解其机制和发现新的药物靶点仍然是更好的治疗的迫切需要。方法:利用GEO数据集筛选哮喘患者血液中的差异表达基因(DEGs)。采用基于汇总数据的孟德尔随机化(SMR)和双样本孟德尔随机化(TSMR),我们确定了哮喘致病基因、致病DNA甲基化位点和影响基因表达的甲基化位点,并与来自每个来源的至少2个大规模GWAS交叉验证。我们利用共定位研究遗传关联,荟萃分析研究数据整合,两步磁共振研究甲基化-基因-哮喘调解机制。通过开放靶标、虚拟筛选和对接来评估药物的可成药性。结果:在哮喘患者血液中发现的954个deg中,CEP95(发现,OR_SMR = 0.94, 95% CI: 0.91 ~ 0.97)、RBM6(发现,OR_SMR = 0.97, 95% CI: 0.95 ~ 0.99)和ITPKB(发现,OR_SMR = 0.82, 95% CI: 0.74 ~ 0.92)的表达增加降低了哮喘的风险,HOXB-AS1(发现,OR_SMR = 1.05, 95% CI: 1.03 ~ 1.07)、ETS1(发现,OR_SMR = 1.62, 95% CI: 1.29 ~ 2.04)和JAK2(发现,OR_SMR = 1.13, 95% CI:1.06-1.21)会增加患哮喘的风险。此外,发现ITPKB、ETS1和JAK2上共有8个甲基化位点影响哮喘。cg16265553位点甲基化的增加部分通过抑制ITPKB表达而增加哮喘的风险。同样,cg13661497位点甲基化的增加完全通过抑制JAK2表达来降低哮喘风险。在肺组织中进一步证实了CEP95、HOXB-AS1和RBM6表达对哮喘的影响。除HOXB-AS1外,其余基因均为潜在的药物靶点。结论:我们的研究强调了特定基因表达和甲基化位点显著影响哮喘风险,并揭示了甲基化-基因-哮喘的潜在机制。这为未来有针对性的功能研究和预防和治疗策略的发展提供了关键证据。
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引用次数: 0
Management and disease burden of children and adults with severe IgE-mediated food allergy: Are adults the lost population? 严重ige介导的食物过敏的儿童和成人的管理和疾病负担:成年人是丢失的人群吗?
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-12-01 DOI: 10.1016/j.waojou.2024.100971
Katharina Blumchen MD , Martin Hutter MSc , Sabine Schnadt MSc , Gregor Bushart PhD , Claudia Mailaender PhD

Background

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.

Objective

Our survey aimed to assess the care situation of pediatric and adult patients with severe, self-reported physician-diagnosed IgE-FA.

Methods

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 (<18 years: proxy report by parents or ≥ 18 years: self-report by adults).

Results

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 < 0.05).

Discussion

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.
背景:在大多数情况下缺乏因果治疗选择,严重的ige介导的食物过敏(IgE-FA)与高疾病负担相关,因为意外摄入过敏原后永久存在过敏反应的风险。迄今为止,只有很少的数据可以比较儿科和成人人口之间的卫生资源和疾病负担。目的:我们的调查旨在评估儿童和成人严重的,自我报告的医生诊断的IgE-FA患者的护理情况。方法:采用在线问卷调查的方式进行调查,调查内容包括32个项目,包括参与者的人口统计、合并症、触发因素、卫生资源的利用、目前的管理和疾病负担。结果:共有367名参与者(n = 237名儿童/父母,n = 130名成人)被纳入自述的医生诊断的IgE-FA和医生处方的肾上腺素自动注射器。紧急培训和制定紧急行动计划在儿科组(81.4%)比成人组(36.2%)更为常见。儿童有更明确的医疗接触点(儿科医生或[儿科]肺科医生,89.0%),而成年人根据他们的fa相关症状去看各种专科医生。成人对过敏原避免(18.5%)、日常FA管理(27.9%)和治疗医生(34.4%)的总体应对策略的不满意程度分别高于儿科组(2.6%/17.0%/14.8%)。讨论:我们的数据显示,在德国,严重IgE-FA的供应普遍不足,成人受影响明显更大。这可能导致该年龄组报告的较高疾病负担。增加更明确的医疗接触点(例如,专门研究食物过敏的合格过敏症专家)——特别是对成年患者群体来说,为这群患者找到可用的治疗选择,并提高一般人群对严重食物过敏的认识,可能会克服这个问题。
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引用次数: 0
Social inequalities in childhood asthma 儿童哮喘的社会不平等
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-12-01 DOI: 10.1016/j.waojou.2024.101010
Angela Pinot de Moira PhD, Adnan Custovic MD, PhD, FMedSci
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).
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.
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.
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.
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.
哮喘是一种复杂的、异质性的疾病,其广泛特征是慢性气道炎症伴不同的呼气气流限制,但有几种亚型由不同(尽管可能重叠)的病理机制支撑。它是儿童最常见的慢性疾病之一,对卫生保健系统和受影响家庭来说是一项重大成本。有证据表明,这一负担的不成比例落在社会经济条件不利的家庭身上。在这篇综述中,我们描述了在弱势的SECs中成长与儿童哮喘诊断和哮喘结局风险增加的关联程度,包括这在地理上和不同哮喘亚型之间的差异。我们还讨论了复杂和相互依赖的介导途径,这些途径可能将不利的SECs与儿童哮喘和哮喘相关的结果联系起来。在高收入国家,在处境不利的中等收入国家长大与儿童哮喘患病率增加之间存在相当一致的关联。然而,有证据表明,这种社会模式在不同的哮喘亚型中是不同的,与处境不利的哮喘相关的哮喘表型不太可能与特应性相关,更有可能从婴儿期开始并持续到青春期。处于不利地位的儿童还与较差的哮喘结局有关,这可能导致处于不利地位的儿童症状持续存在。在低收入和中等收入国家(LMICs),这种模式变化更大,数据也更有限,但有一些证据表明,处境不利的SECs和特应性哮喘同样呈负相关。哮喘结局也存在明显差异,低收入国家尽管哮喘患病率较低,但哮喘相关发病率和死亡率却高得不成比例。缺乏获得基本药物和适当护理的机会无疑是造成这些差异的原因。导致哮喘社会不平等的途径是复杂和相互依存的,而且尚未完全了解。显然需要进一步研究潜在介导途径的相对重要性,包括这些途径在整个生命过程和哮喘亚型之间的差异。更好地理解这些途径将有助于确定最有效的干预政策切入点,最终减少整个生命过程中的不平等。
{"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}
引用次数: 0
Fel d 1 specific IgE measurement for dog exclusive owners co-sensitized to dog and cat 对狗和猫共同敏感的狗专用主人的1特异性IgE测量
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-12-01 DOI: 10.1016/j.waojou.2024.101007
Lin Liang MD , Ah-Reum Hwang MS , Yoon Ji Shin BS , Kyoung Yong Jeong PhD , Kyung Hee Park MD, PhD , Jae-Hyun Lee MD, PhD , Jung-Won Park MD, PhD

Background

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.

Methods

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.

Results

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.

Conclusions

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.
背景:罪魁祸首过敏原的诊断取决于暴露、暴露时的症状和特异性IgE (sIgE)的存在。宠物过敏原是粘性的,可以使没有收养史的个体敏感。专门养狗的人经常同时展示狗(e5)和猫的皮屑sIgE (e1)。我们评估了Fel d1 sIgE (e94)的测量是否可以通过交叉反应区分猫的真敏化和假阳性。方法选取31例专门养狗的呼吸道过敏患者作为研究对象。免疫cap检测e5、e1和e94。ELISA法测定交叉反应性。结果81%(25/31)患者e5和e1同时阳性,8例患者e94同时阳性。在e94阳性中,猫皮屑对猫sIgE的最大抑制作用更高(94%对88%),IC50比狗皮屑低(6.5对737.9 BAU/mL)。相反,在e94阴性的情况下,与猫皮屑相比,狗皮屑对猫皮屑sIgE的最大抑制作用更高(71.9%对56.2%),IC50更低(172对1947 BAU/mL)。在e94阳性组中,狗皮屑对狗sIgE的最大抑制作用高于猫皮屑(91.5 vs 76.1%), IC50 (10.6 vs 1679 BAU/mL)低于猫皮屑,而在e94阴性组中,猫皮屑的IC50无法确定。结论:即使在只养狗的个体中,对猫的真正共敏也很明显。e94阳性结果可以通过交叉反应区分这些患者的真实猫致敏和假阳性,强调了综合过敏评估的重要性。
{"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 IC<sub>50</sub> (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 IC<sub>50</sub> (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 IC<sub>50</sub> (10.6 vs 1679 BAU/mL) compared to cat dander, whereas in the e94 negative, the IC<sub>50</sub> 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}
引用次数: 0
Perceptions of the impact of individual allergic rhinitis symptoms: A survey of ARIA clinical experts 个体变应性鼻炎症状影响的认知:对ARIA临床专家的调查。
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-12-01 DOI: 10.1016/j.waojou.2024.100999
Sara Gil-Mata MD , Tatiana Teixeira MD , Anna Bedbrook BSc , Jean Bousquet PhD , Bernardo Sousa-Pinto PhD , Rafael José Vieira MD

Background

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.

Methods

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.

Results

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.

Conclusion

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.
背景:变应性鼻炎(AR)是一种非常普遍的疾病。我们的目的是评估医生认为AR患者最令人烦恼的症状。方法:我们对变应性鼻炎及其对哮喘的影响(ARIA)倡议的所有成员发送的在线问卷进行了横断面研究。该调查包括医生对患者AR症状的看法以及他们自己的AR症状的问题。结果:在401名受访者中,155名(38.7%)报告有AR。ARIA成员报告鼻腔症状是他们自己经历过的最常见(89.7%)和最麻烦(80.0%)的症状。同样,ARIA成员报告的鼻腔症状在他们的患者中最常见(有AR的成员中为94.8%,没有AR的成员中为96.0%)和最麻烦(有AR的成员中为57.0%,没有AR的成员中为67.9%)。我们发现医生自己的症状与患者认为最令人烦恼的症状之间存在显著关联(p = 0.001)。结论:医生认为鼻部症状是AR患者最常见和最麻烦的症状。医生对AR的个人经历可能会影响他们对患者症状的感知。
{"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}
引用次数: 0
Allergic disease and keratoconus: A two-sample univariable and multivariable Mendelian randomization study 过敏性疾病与角膜病:一项双样本单变量和多变量孟德尔随机研究
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-11-22 DOI: 10.1016/j.waojou.2024.100993
Hanlu Xu , Yajing Wen , Huikang Zheng , Dan Jiang , Wei Chen

Background

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.

Methods

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.

Results

The causal odds ratio (OR) estimate of genetically determined KC was 1.66 (95% CI: 1.32–2.08; P < 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 < 0.001) for AR and 1.30 (95% CI: 1.17–1.45, P < 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.

Conclusions

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.
背景越来越多的证据表明,过敏是角膜炎的一个危险因素。然而,过敏性疾病与角膜病之间的关系仍存在争议。我们进行了一项双样本孟德尔随机化(MR)研究,以确定 4 种过敏性疾病(过敏性结膜炎、过敏性哮喘、过敏性鼻炎和特应性皮炎)与角膜炎之间的推定因果关系。方法从过敏性结膜炎(AC)(20958 个病例和 356319 个对照组)、过敏性哮喘(AA)(9631 个病例和 210122 个对照组)、过敏性鼻炎(AR)和特应性皮炎的全基因组关联研究(GWAS)中获得汇总统计数据、过敏性鼻炎(AR)(11009 个病例和 359149 个对照组)、特应性皮炎(AD)(13473 个病例和 336589 个对照组)、角膜炎(KC)(2116 个病例和 24626 个对照组)以及 91 种循环炎性细胞因子(n = 14824)。进行了双样本单变量和多变量 MR 分析。结果由基因决定的 KC 的因果几率(OR)估计值为 1.AC为1.66 (95% CI: 1.32-2.08; P < 0.001),AA为1.29 (95% CI: 1.10-1.51, P = 0.0014),AR为1.39 (95% CI: 1.15-1.68; P < 0.001),AD为1.30 (95% CI: 1.17-1.45, P < 0.001)。多变量 MR 显示,在对其他过敏性疾病进行调节后,AC 与 KC 之间存在提示性关联(OR 1.61;95% CI:1.10-2.34;P 调整 = 0.054)。结论我们的研究结果为 AC 与 KC 之间的潜在因果关系提供了证据。AC 对 KC 的影响可能是通过本研究中未包括的其他全身性炎症细胞因子或其他机制介导的。这些研究结果可能有助于制定预防和干预策略,降低 AC 患者罹患 KC 的风险。
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引用次数: 0
Comparing pharmacists versus allergists in low-risk penicillin allergy delabelling: The Hong Kong Penicillin Allergy Pharmacist Initiative (HK-PAPI) 比较药剂师与过敏症专科医生在低风险青霉素过敏脱敏中的作用:香港青霉素过敏药剂师计划 (HK-PAPI)
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-11-21 DOI: 10.1016/j.waojou.2024.101003
James K.Y. Hooi MBChB , Marshall C.H. Low BPharm , Jonathan C.L. To BPharm , Hugo W.F. Mak MBBS , Mandy M. Choi BPharm , Chris C.P. Tam BPharm , Raymond W.M. Mak MSc , Vincent K.C. Wong MPharm , Timo C.C. Chan MClinPharm , Andrew W.T. Li MClinPharm , Charlie C.Y. Mak MClinPharm , Valerie Chiang MBBS , Gordon K.H. Chu MBBS , Jane C.Y. Wong MBBS , Philip H. Li MD

Background

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.
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.

Methods

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.

Results

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 < 0.001) or allergists (37.2 [SD:22.2] to 29.1 [SD:22.4], p < 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 < 0.001).

Conclusions

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.
背景对青霉素过敏与多种不良后果和抗微生物抗药性的产生有关。由于对过敏专科服务的巨大需求,药剂师倡议,如香港青霉素过敏药剂师倡议(HK-PAPI)已被提倡。方法对所有转诊的低风险青霉素过敏成人患者进行随机分组,由药剂师或过敏学家按照 1:3 的比例进行评估。结果在转诊的 323 名患者中,96.3%(311/323)的患者完成了青霉素过敏评估(药剂师:83 [24.3%] vs 过敏症专家:228 [66.7%])。总体而言,93.6%(291/311)的患者被除名,药剂师和过敏学家的评估结果无差异(92.8% vs 93.9%,p = 0.729)。两组患者均未出现严重或全身性反应。由药剂师(43.4 [SD:29.1] 对 10.5 [SD:5.93], p <0.001)或过敏症专家(37.2 [SD:22.2] 对 29.1 [SD:22.4], p <0.001)评估的患者的 HR-QoL 均有所改善,DrHy-Q 评分反映了这一点。结论 在低风险青霉素过敏症患者中,由药剂师(与过敏症专家)进行评估和脱敏治疗的效果和安全性相当。此外,接受药剂师评估的患者甚至在 HR-QoL 方面有明显改善,这凸显了多学科过敏措施的潜力。
{"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}
引用次数: 0
Levels of total IgE versus specific IgE during childhood for defining and predicting T2-high asthma 儿童期总 IgE 水平与特异性 IgE 水平对比,用于定义和预测 T2 高哮喘
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-11-21 DOI: 10.1016/j.waojou.2024.100994
Tamo Sultan MD , Frederikke Skov MD , Nicklas Brustad MD, PhD , Nilo Vahman MD, PhD , Jakob Stokholm MD, PhD , Klaus Bønnelykke MD, PhD , Ann-Marie Malby Schoos MD, PhD, DMSc , Bo Chawes MD, PhD, DMSc

Background

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.

Objective

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”.

Methods

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.

Results

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).

Conclusion

Elevated tIgE and sIgE are equally useful stand-alone biomarkers for defining and predicting risk of T2-high asthma in childhood.
背景T2-高哮喘的特征是血嗜酸性粒细胞(b-eos)升高,和/或呼出一氧化氮(FeNO)分数升高,和/或 "过敏驱动",而 "过敏驱动 "尚未明确定义。方法 我们利用 COPSAC2000(n = 411)和 COPSAC2010(n = 700)母婴队列中的数据,重复测量了儿童时期的 tIgE、sIgE、b-eos 和 FeNO。我们通过 b-eos 升高(≥0.3 × 109/L)和/或 FeNO 升高(≥20 ppb)来定义 T2 高哮喘,并使用逻辑回归分析了 7/10/13/18 岁时 tIgE(特定年龄临界值)和 sIgE(≥0.35 kU/L)升高的相关性。此外,我们还使用逻辑回归和 ROC 模型分析了 0-4 岁时 tIgE 和 sIgE 升高与日后 T2 高哮喘风险之间的关联。使用Vuong似然比检验、Akaike或贝叶斯信息标准,总体上并不倾向于将tIgE和sIgE结合起来,而不是单独使用tIgE或sIgE。此外,0-4 岁时的 tIgE 升高与所有时间点的 T2 高哮喘风险相关(AUC = 0.63-0.70,灵敏度 = 0.62-0.81,特异性 = 0.57-0.78),而 0-4 岁时的 sIgE 升高仅与 18 岁时的 T2 高哮喘相关(AUC = 0.66,灵敏度 = 0.45,特异性 = 0.88)。tIgE和sIgE的AUC值无明显差异(DeLong检验)。
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引用次数: 0
Dissecting the pathogenic effects of smoking in blood DNA methylation on allergic diseases 剖析吸烟在血液 DNA 甲基化中对过敏性疾病的致病作用
IF 3.9 2区 医学 Q2 ALLERGY Pub Date : 2024-11-21 DOI: 10.1016/j.waojou.2024.100995
Junhao Tu PhD, MD , Wei Wan PhD, MD , Binxiang Tang MSc , Fan Jiang MSc , Jinyang Wen PhD, MD , Qing Luo PhD, MD , Jing Ye PhD, MD

Background

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.

Methods

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.

Results

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.

Conclusions

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.
背景哮喘和过敏性鼻炎等过敏性疾病是全球面临的重大健康挑战。方法我们利用FinnGen数据库中的数据进行了双样本孟德尔随机化(MR)分析,研究吸烟行为与各种过敏性疾病之间的关系。此外,我们还研究了 DNA 甲基化(CpG 位点)与过敏性疾病的关系,并将 mQTLs 作为表观遗传学的替代物。结果在我们的基因组磁共振分析中,发现吸烟行为(如开始吸烟和每天吸烟数量)与哮喘风险的增加存在因果关系。此外,有提示性证据表明,开始吸烟与特应性接触性皮炎有关。我们的表观遗传 MR 分析发现,通过 mQTLs 评估的 46 个 CpG 位点的甲基化变化与哮喘风险显著相关。值得注意的是,cg17272563(PRRT1)、cg03689048(BAT3)、cg20069688(STK19)和 cg20513976(LIME1)被确定具有交叉过敏效应。我们的研究强调了吸烟行为与过敏性疾病(尤其是哮喘)之间在遗传和表观遗传方面的关联。我们发现了几个与 DNA 甲基化相关的 CpG 位点,如 cg03689048(BAT3)、cg17272563(PRRT1)和 cg20069688(STK19),这些位点显示了跨过敏潜能和反向因果关系。
{"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}
引用次数: 0
期刊
World Allergy Organization Journal
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