Journal of Allergy and Clinical Immunology最新文献_第10页

Can sputum eosinophils predict a poor response to mepolizumab? 痰中嗜酸性粒细胞能否预测对美泊利珠单抗的不良反应？

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.04.013

引用次数: 0

Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis 鼻内抗组胺药和皮质类固醇治疗过敏性鼻炎：系统综述和荟萃分析。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.04.016

Background

There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR).

Objectives

We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR.

Methods

The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Results

This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered “high” in 6 of 46 analyses, “moderate” in 23 of 46 analyses, and “low”/“very low” in 17 of 46 analyses.

Conclusions

Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

背景：目前还没有足够的系统证据表明单种鼻内用药对过敏性鼻炎（AR）的疗效：进行一项系统性研究，比较单个鼻内皮质类固醇激素和抗组胺药与安慰剂在改善常年性或季节性过敏性鼻炎患者的鼻部和眼部症状以及与鼻结膜炎相关的生活质量方面的疗效：我们在四个电子文献数据库和三个临床试验数据库中搜索了以下随机对照试验：(i) 评估季节性或常年性 AR 成年患者的试验；(ii) 比较鼻内皮质类固醇激素或抗组胺药与安慰剂的使用情况。评估的结果包括鼻部症状总评分（TNSS）、眼部症状总评分（TOSS）和鼻结膜炎生活质量问卷（RQLQ）。我们对每种药物和结果的平均差异进行了随机效应荟萃分析。我们采用 GRADE 方法评估了证据的确定性：我们纳入了 151 项主要研究，其中大部分研究评估的是季节性 AR 患者，偏倚风险不明确或较高。无论是常年性还是季节性AR，大多数评估的治疗方法都比安慰剂更有效。在季节性 AR 中，阿折司亭-氟替卡松、糠酸氟替卡松和丙酸氟替卡松是最有可能使 TNSS 和 RQLQ 中度或大幅改善的药物。阿折拉斯汀-氟替卡松导致 TOSS 中度或大幅改善的概率最高。总体而言，6/46 项分析认为证据确定性 "高"，23/46 项分析认为证据确定性 "中等"，17/46 项分析认为证据确定性 "低"/"极低"：结论：大多数鼻内用药都能有效改善鼻炎症状和生活质量。然而，相关证据的确定性存在相关差异。

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引用次数: 0

PEGylated liposomes for diagnosis of polyethylene glycol allergy 用于诊断聚乙二醇过敏的 PEG 化脂质体

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.03.030

Background

Polyethylene glycol (PEG) is a nonprotein polymer that is present in its native (unbound) form as an excipient in a range of products. It is increasingly being utilized clinically in the form of PEGylated liposomal medications and vaccines. PEG is the cause of anaphylaxis in a small percentage of drug reactions; however, diagnosis of PEG allergy is complicated by the variable and poor diagnostic performance of current skin testing protocols.

Objective

We assessed the diagnostic performance of PEGylated lipid medications as an alternative to currently described tests that use medications containing PEG excipients.

Methods

Nine patients with a strong history of PEG allergy were evaluated by skin testing with a panel of PEG-containing medications and with a PEGylated lipid nanoparticle vaccine (BNT162b2). Reactivity of basophils to unbound and liposomal PEG was assessed ex vivo, and specificity of basophil responses to PEGylated liposomes was investigated with a competitive inhibition assay. More detailed information is provided in this article’s Methods section in the Online Repository available at www.jacionline.org.

Results

Despite compelling histories of anaphylaxis to PEG-containing medications, only 2 (22%) of 9 patients were skin test positive for purified PEG or their index reaction-indicated PEG-containing compound. Conversely, all 9 patients were skin test positive or basophil activation test positive to PEGylated liposomal BNT162b2 vaccine. Concordantly, PEGylated liposomal drugs (BNT162b2 vaccine and PEGylated liposomal doxorubicin), but not purified PEG2000, consistently induced basophil activation ex vivo in patients with PEG allergy but not in nonallergic controls. Basophil reactivity to PEGylated nanoparticles competitively inhibited by preincubation of basophils with native PEG2000.

Conclusion

Presentation of PEG on the surface of a lipid nanoparticle increases its in vivo and ex vivo allergenicity, and improves diagnosis of PEG allergy.

背景：聚乙二醇 (PEG) 是一种非蛋白质聚合物，它以原生（非结合）形式作为赋形剂存在于一系列产品中，并越来越多地以 PEG 脂质体药物和疫苗的形式用于临床。在一小部分药物反应中，PEG 是导致过敏性休克的原因，但由于目前的皮肤测试方案多变且诊断效果不佳，导致 PEG 过敏的诊断变得复杂：我们评估了 PEG 化脂质药物的诊断性能，以替代目前使用含有 PEG 辅料的药物进行的测试：九名有 PEG 过敏史的患者接受了含 PEG 药物和 PEG 化脂质纳米颗粒疫苗 (BNT162b2) 的皮试评估。嗜碱性粒细胞与未结合和脂质体 PEG 的反应性在体外进行了评估，嗜碱性粒细胞对 PEG 化脂质体反应的特异性则通过竞争性抑制试验进行了研究。详细方法请参见本文在线资料库中的方法部分：尽管有令人信服的含 PEG 药物过敏性休克病史，但九名患者中只有两人（22%）对纯化的 PEG 或其指数反应显示的含 PEG 化合物皮试呈阳性。相反，九名患者中有九名（100%）对 PEG 化脂质体 BNT162b2 疫苗的皮试呈阳性或嗜碱性粒细胞活化测试呈阳性。同样，PEG 化脂质体药物（BNT162b2 疫苗和 PEG 化脂质体多柔比星）而非纯化的 PEG2000 可持续诱导 PEG 过敏患者体内外的嗜碱性粒细胞活化，而非过敏对照组则不能。嗜碱性粒细胞与原生 PEG2000 预孵育可竞争性抑制嗜碱性粒细胞对 PEG 化纳米颗粒的反应：我们证明，在脂质纳米粒子表面添加 PEG 会增加其体内和体外过敏性，并改善 PEG 过敏的诊断。

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引用次数: 0

Staphylococcus aureus–specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis–like flares in mice 金黄色葡萄球菌特异性皮肤常驻记忆 T 细胞可防止细菌定植，但会加剧小鼠特应性皮炎样发作。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.03.032

Background

The contribution of Staphylococcus aureus to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored.

Objectives

This study sought to reappraise the main bacterial factors and underlying immune mechanisms by which S aureus triggers AD-like inflammation.

Methods

This study capitalized on a preclinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury.

Results

The development of S aureus–induced dermatitis depended on the nature of the S aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and nonsecreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor apoptosis-associated speck-like protein containing a CARD domain– and monocyte/macrophage-deficient animals, but not in T- and B-cell–deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S aureus, and an accumulation of S aureus–specific γδ and CD4⁺ tissue resident memory T cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis on new bacteria exposures, but also, protected the mice from persistent bacterial colonization.

Conclusions

These data highlight the induction of unique AD-like inflammation, with the generation of proinflammatory but protective tissue resident memory T cells in a context of natural exposure to pathogenic S aureus strains.

背景：金黄色葡萄球菌（S. aureus）对特应性皮炎（AD）病情加重的作用已被广泛记录，但其作为特应性皮炎皮肤症状主要诱因的作用仍未得到充分探讨：目的：重新评估金黄色葡萄球菌引发 AD 类炎症的主要细菌因素和潜在免疫机制：方法：我们利用临床前模型，在没有任何实验性皮肤损伤的情况下，应用不同的临床分离菌株：结果：我们发现，金黄色葡萄球菌诱发皮炎的发展取决于金黄色葡萄球菌菌株的性质、活力、应用细菌悬浮液的浓度、分泌和非分泌因子的产生以及附属基因调控法定量感应系统的激活。此外，在炎性体适配蛋白 ASC 和单核细胞/巨噬细胞缺陷的小鼠中，炎性体适配蛋白 ASC 和单核细胞/巨噬细胞缺陷的小鼠显著抑制了上升性皮炎，而在 T 细胞和 B 细胞缺陷的小鼠中则没有抑制作用，这表明先天性反应在诱导皮肤炎症中发挥了重要作用。然而，细菌暴露会产生针对金黄色葡萄球菌的强大适应性免疫反应，并在先前的皮炎部位积累金黄色葡萄球菌特异性γδ和CD4+组织常驻记忆T细胞（Trm）。后者在新的细菌暴露时会加剧 AD 型皮炎的复发，但同时也保护小鼠免受持续的细菌定植：这些数据突出表明，在自然暴露于致病性金黄色葡萄球菌菌株的情况下，会诱发独特的 AD 类炎症，并产生促炎症但具有保护作用的 Trm 细胞。

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引用次数: 0

News & Notes-AAAAI 新闻与说明-AAAAI

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/S0091-6749(24)00646-8

引用次数: 0

A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice Themis 基因突变导致 CC027 小鼠口服花生后过敏性休克的严重程度

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.03.027

Background

The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice.

Objective

This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice.

Methods

A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains.

Results

Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge—6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8⁺, CD4⁺, and CD4⁺CD25⁺CD127⁻ regulatory T cells.

Conclusions

Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.

背景花生过敏的发生是遗传和环境因素共同作用的结果，但特异性基因却难以确定。本研究旨在确定CC027小鼠口服花生诱发过敏性休克的遗传基础。方法设计了一个CC027和C3H小鼠之间的遗传图谱群体，以确定驱动口服过敏性休克的遗传因素。共产生了356只CC027xC3H回交小鼠，对花生致敏，然后通过口服花生进行挑战。对所有小鼠的过敏性休克和花生特异性 IgE 进行了量化。结果 77%的回交小鼠对花生没有过敏反应，19%出现中度过敏反应，4%出现严重过敏反应。有 8 个基因位点与花生挑战反应的变化有关，其中 6 个与过敏性休克（体温下降）有关，2 个与花生特异性 IgE 水平有关。有 2 个主要基因位点对急性过敏性休克的严重程度有多方面影响，其中 CC027 等位基因与较差的预后有关。在其中一个基因位点上，CC027 在 Themis 基因中有一个私人遗传变异。与描述的 Themis 功能一致，我们发现 CC027 小鼠有更多的未成熟 T 细胞，CD8+、CD4+ 和 CD4+CD25+CD127- 调节性 T 细胞较少。

{"title":"A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice","authors":"","doi":"10.1016/j.jaci.2024.03.027","DOIUrl":"10.1016/j.jaci.2024.03.027","url":null,"abstract":"<div><h3>Background</h3><p>The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice.</p></div><div><h3>Objective</h3><p>This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice.</p></div><div><h3>Methods</h3><p>A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains.</p></div><div><h3>Results</h3><p>Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge—6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the <em>Themis</em> gene. Consistent with described functions of <em>Themis</em>, we found that CC027 mice have more immature T cells with fewer CD8<sup>+</sup>, CD4<sup>+</sup>, and CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>−</sup> regulatory T cells.</p></div><div><h3>Conclusions</h3><p>Our results demonstrate a key role for <em>Themis</em> in the orally reactive CC027 mouse model of peanut allergy.</p></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thymic stromal lymphopoietin induces IL-4/IL-13 from T cells to promote sebum secretion and adipose loss 胸腺基质淋巴生成素诱导 T 细胞产生 IL-4/IL-13，促进皮脂分泌和脂肪流失

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2023.11.923

Background

The cytokine TSLP promotes type 2 immune responses and can induce adipose loss by stimulating lipid loss from the skin through sebum secretion by sebaceous glands, which enhances the skin barrier. However, the mechanism by which TSLP upregulates sebaceous gland function is unknown.

Objectives

This study investigated the mechanism by which TSLP stimulates sebum secretion and adipose loss.

Methods

RNA-sequencing analysis was performed on sebaceous glands isolated by laser capture microdissection and single-cell RNA-sequencing analysis was performed on sorted skin T cells. Sebocyte function was analyzed by histological analysis and sebum secretion in vivo and by measuring lipogenesis and proliferation in vitro.

Results

This study found that TSLP sequentially stimulated the expression of lipogenesis genes followed by cell death genes in sebaceous glands to induce holocrine secretion of sebum. TSLP did not affect sebaceous gland activity directly. Rather, single-cell RNA-sequencing revealed that TSLP recruited distinct T-cell clusters that produce IL-4 and IL-13, which were necessary for TSLP-induced adipose loss and sebum secretion. Moreover, IL-13 was sufficient to cause sebum secretion and adipose loss in vivo and to induce lipogenesis and proliferation of a human sebocyte cell line in vitro.

Conclusions

This study proposes that TSLP stimulates T cells to deliver IL-4 and IL-13 to sebaceous glands, which enhances sebaceous gland function, turnover, and subsequent adipose loss.

背景细胞因子胸腺基质淋巴细胞生成素（TSLP）可促进2型免疫反应，并通过刺激皮脂腺分泌皮脂以增强皮肤屏障，从而诱导脂肪流失。然而，TSLP 上调皮脂腺功能的机制尚不清楚。在此，我们研究了 TSLP 刺激皮脂分泌和脂肪流失的机制。通过组织学分析和体内皮脂分泌以及体外脂肪生成和增殖测量分析了皮脂腺细胞的功能。结果我们发现，TSLP 依次刺激皮脂腺中脂肪生成基因和细胞死亡基因的表达，从而诱导皮脂的全分泌。TSLP 并不直接影响皮脂腺的活性。相反，单细胞RNA测序显示，TSLP招募了产生IL-4和IL-13的不同T细胞集群，而IL-4和IL-13是TSLP诱导脂肪流失和皮脂分泌所必需的。此外，IL-13 足以导致体内皮脂分泌和脂肪流失，并诱导体外人类皮脂细胞系的脂肪生成和增殖。临床意义因此，IL-4 和 IL-13 除了能引起皮肤炎症外，还能促进皮脂分泌，而皮脂是皮肤屏障的重要组成部分。

{"title":"Thymic stromal lymphopoietin induces IL-4/IL-13 from T cells to promote sebum secretion and adipose loss","authors":"","doi":"10.1016/j.jaci.2023.11.923","DOIUrl":"10.1016/j.jaci.2023.11.923","url":null,"abstract":"<div><h3>Background</h3><p><span><span>The cytokine TSLP promotes type 2 immune responses and can induce </span>adipose<span> loss by stimulating lipid loss from the skin through </span></span>sebum<span><span> secretion by sebaceous glands, which enhances the skin barrier. However, the mechanism by which </span>TSLP upregulates sebaceous gland function is unknown.</span></p></div><div><h3>Objectives</h3><p><span><span>This study investigated the mechanism by which TSLP stimulates </span>sebum secretion and </span>adipose loss.</p></div><div><h3>Methods</h3><p><span><span>RNA-sequencing analysis was performed on sebaceous glands isolated by </span>laser capture microdissection<span> and single-cell RNA-sequencing analysis was performed on sorted skin T cells<span>. Sebocyte function was analyzed by histological analysis and sebum secretion </span></span></span><em>in vivo</em><span> and by measuring lipogenesis and proliferation </span><em>in vitro.</em></p></div><div><h3>Results</h3><p><span><span><span>This study found that TSLP sequentially stimulated the expression of </span>lipogenesis<span><span><span> genes followed by cell death genes in sebaceous glands to induce holocrine secretion of </span>sebum<span>. TSLP did not affect sebaceous gland activity directly. Rather, single-cell RNA-sequencing revealed that TSLP recruited distinct T-cell clusters that produce IL-4 and IL-13, which were necessary for TSLP-induced </span></span>adipose loss and </span></span>sebum secretion<span>. Moreover, IL-13 was sufficient to cause sebum secretion and adipose loss </span></span><em>in vivo</em><span> and to induce lipogenesis and proliferation of a human sebocyte cell line </span><em>in vitro</em>.</p></div><div><h3>Conclusions</h3><p>This study proposes that TSLP stimulates T cells<span> to deliver IL-4 and IL-13 to sebaceous glands, which enhances sebaceous gland function, turnover, and subsequent adipose loss.</span></p></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139059495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A health inequality analysis of childhood asthma prevalence in urban Australia 澳大利亚城市儿童哮喘发病率的健康不平等分析。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.01.023

Background

Long-standing health inequalities in Australian society that were exposed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were described as “fault lines” in a recent call to action by a consortium of philanthropic organizations. With asthma a major contributor to childhood disease burden, studies of its spatial epidemiology can provide valuable insights into the emergence of health inequalities early in life.

Objective

The aims of this study were to characterize the spatial variation of asthma prevalence among children living within Australia’s 4 largest cities and quantify the relative contributions of climatic and environmental factors, outdoor air pollution, and socioeconomic status in determining this variation.

Methods

A Bayesian model with spatial smoothing was developed to regress ecologic health status data from the 2021 Australian Census against groups of explanatory covariates intended to represent mechanistic pathways.

Results

The prevalence of asthma in children aged 5 to 14 years averages 7.9%, 8.2%, 8.5%, and 7.6% in Sydney, Melbourne, Brisbane, and Perth, respectively. This small inter-city variation contrasts against marked intracity variation at the small-area level, which ranges from 6% to 12% between the least and most affected locations in each. Statistical variance decomposition on a subsample of Australian-born, nonindigenous children attributes 66% of the intracity spatial variation to the assembled covariates. Of these covariates, climatic and environmental factors contribute 30%, outdoor air pollution contributes 19%, and areal socioeconomic status contributes the remaining 51%.

Conclusion

Geographic health inequalities in the prevalence of childhood asthma within Australia’s largest cities reflect a complex interplay of factors, among which socioeconomic status is a principal determinant.

背景：严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）大流行暴露出澳大利亚社会长期存在的健康不平等问题，慈善组织联盟最近呼吁采取行动，将这些问题描述为 "断层线"。哮喘是造成儿童疾病负担的一个主要因素，对哮喘空间流行病学的研究可以为了解生命早期健康不平等的出现提供有价值的见解：本研究旨在描述澳大利亚四大城市儿童哮喘发病率的空间变化特征，并量化气候和环境因素、室外空气污染以及社会经济状况在决定这种变化时的相对作用：方法：建立了一个具有空间平滑功能的贝叶斯模型，将 2021 年澳大利亚人口普查中的生态健康状况数据与旨在代表机理途径的解释性协变量组进行回归：悉尼、墨尔本、布里斯班和珀斯 5 至 14 岁儿童的哮喘患病率平均分别为 7.9%、8.2%、8.5% 和 7.6%。这种城市间的微小差异与城市内部小区域层面的显著差异形成鲜明对比，每个城市中受影响最小和最严重地区之间的差异从 6% 到 12% 不等。对澳大利亚出生的非土著儿童的子样本进行统计方差分解后发现，66%的城市内空间变化归因于所收集的协变量。在这些协变量中，气候和环境因素占30%，室外空气污染占19%，其余的51%归因于地区社会经济状况：结论：澳大利亚最大城市中儿童哮喘发病率的地域健康不平等反映了各种因素之间复杂的相互作用，其中社会经济地位是主要的决定因素。

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引用次数: 0

Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria 鉴定丙酮酸和马来酸作为慢性荨麻疹疾病活动和预后的潜在标志物。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.01.032

Background

Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of patients with CU has not been reported.

Objective

We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy.

Methods

Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow–derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively.

Results

We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N⁶-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H₁ antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo.

Conclusions

Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.

背景：基于人群的研究强调了慢性荨麻疹（CU）与代谢综合征之间的联系，并揭示了CU的代谢改变。然而，据我们所知，目前还没有关于大样本慢性荨麻疹患者代谢组学综合研究的报道：我们试图探索潜在的代谢亚型和新的代谢物生物标志物，以用于 CU 的诊断和治疗：收集了 80 名 CU 患者和 82 名健康对照者的血浆样本，进行代谢组学量化和生物信息学分析。为了验证研究结果，研究人员对由 144 名 CU 患者组成的另一个独立队列进行了研究。骨髓肥大细胞和IgE诱导的被动皮肤过敏性休克小鼠分别被用于体外和体内实验：结果：我们观察到CU患者和健康对照组之间存在明显的代谢组差异。同时，差异代谢物N6-乙酰基-赖氨酸、l-天门冬氨酸、马来酸和丙酮酸被用于构建随机森林分类器，其接收者操作特征曲线下面积值大于0.85，表明它们具有作为CU诊断生物标志物的潜力。更重要的是，通过探索CU的潜在代谢亚型，我们发现丙酮酸和马来酸的低丰度与CU的活动性、第二代H1抗组胺药的疗效差和无复发时间短显著相关。这些结果在独立队列中得到了验证。此外，在体外和体内补充丙酮酸或马来酸盐可明显减轻IgE介导的肥大细胞活化：结论：血浆丙酮酸和马来酸可能是预测CU患者疾病活动性、疗效和预后的有效生物标志物。

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引用次数: 0

Comparative safety of oral Janus kinase inhibitors and dupilumab in patients with atopic dermatitis: a population-based cohort study. 特应性皮炎患者口服 Janus 激酶抑制剂和杜匹单抗的安全性比较：一项基于人群的队列研究。

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology

Pub Date : 2024-08-01 DOI: 10.1016/j.jaci.2024.07.019

Serena Yun-Chen Tsai, Wanda Phipatanakul, Elena B Hawryluk, Michiko K Oyoshi, Lynda C Schneider, Kevin Sheng-Kai Ma

Background: Systemic Janus kinase inhibitors (JAKi) and dupilumab both have emerged as promising therapeutics for atopic dermatitis (AD). While dupilumab has a favorable safety profile, use of oral JAKi has been established in other diseases that carry potential comorbid susceptibilities that influence safety.

Objective: To provide real-world evidence of the safety of oral JAKi in AD patients.

Methods: The study used observational data from TriNetX (Cambridge, Massachusetts). Patients with AD treated with either oral JAKi (upadacitinib, abrocitinib, and baricitinib) or dupilumab were enrolled. The two treatment groups were propensity-score matched 1:1 based on demographics, comorbidities, and prior medications. Safety outcomes within two years after the initiation of medications were measured by hazard ratios with 95% confidence intervals.

Results: A total of 14,716 patients were included, with 942 patients treated with oral JAKi and 13,774 with dupilumab. The two treatment groups included 938 patients after matching. Treatment with oral JAKi was not associated with increased risks of mortality, malignancies, major adverse cardiovascular events, venous thromboembolism, renal events, or serious gastrointestinal events. However, patients receiving oral JAKi showed significantly higher risks of skin and subcutaneous tissue infection, herpes infection, acne, cytopenia, and hyperlipidemia, whereas the risk of ophthalmic complications was higher in those receiving dupilumab.

Conclusion: This study found that oral JAKi did not exhibit concerning safety issues in treating patients with AD but increased the risk of infections and laboratory abnormalities. Long-term follow-up data are required to validate these findings.

背景：全身性 Janus 激酶抑制剂（JAKi）和杜比单抗都已成为治疗特应性皮炎（AD）的有前途的疗法。尽管杜比鲁单抗具有良好的安全性，但口服 JAKi 已被用于其他疾病，而这些疾病具有影响安全性的潜在并发症：为口服 JAKi 在 AD 患者中的安全性提供实际证据：研究使用了 TriNetX（马萨诸塞州剑桥市）的观察数据。接受口服 JAKi（upadacitinib、abrocitinib 和 baricitinib）或 dupilumab 治疗的 AD 患者被纳入研究。两个治疗组根据人口统计学、合并症和既往用药情况进行了倾向得分匹配，比例为1:1。用危险比和95%置信区间来衡量用药后两年内的安全性结果：共纳入14716名患者，其中942名患者接受了口服JAKi治疗，13774名患者接受了dupilumab治疗。两个治疗组在匹配后共纳入938名患者。口服JAKi治疗与死亡率、恶性肿瘤、主要不良心血管事件、静脉血栓栓塞、肾脏事件或严重胃肠道事件的风险增加无关。然而，接受口服JAKi治疗的患者发生皮肤和皮下组织感染、疱疹感染、痤疮、全血细胞减少症和高脂血症的风险明显较高，而接受dupilumab治疗的患者发生眼科并发症的风险较高：这项研究发现，口服JAKi在治疗AD患者时并没有表现出令人担忧的安全性问题，但会增加感染和实验室异常的风险。需要长期随访数据来验证这些发现。

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