高T型哮喘表型的全生命周期表现
2022/02/28
摘要
原理：在成人中，个性化哮喘治疗针对高T2和嗜酸性哮喘表型的患者。目前尚不清楚这种分类在儿童身上是否可行。
目的：用易于获得的生物标记物定义高T2哮喘，并比较所有年龄段的表型。
方法：在多中心临床全年龄哮喘队列（ALLIANCE）中，招募了1125名参与者（n=776名哮喘患者，n=349名对照），并随访2年（成人1年）。在基线检查和随访时，进行了广泛的临床特征分析（问卷调查、血液分类计数、过敏测试、肺功能和痰诱导（成人）。用LPS或抗CD3/CD28刺激全血后测定白细胞介素（IL）-4、IL-5和IL-13。
检测和主要结果：根据血液嗜酸性粒细胞计数和过敏原特异性血清IgE抗体（sIgE），将患者分为四种相互排斥的表型：“仅特应性”、“仅嗜酸性粒细胞”、“高T2”（嗜酸性粒细胞+特应性）和“T2低”（既不嗜酸性粒细胞也不特应性）。高T2表型存在于所有年龄段，甚至在非常年幼的儿童中，即使在随访2年后，T2高表型仍在很大程度上持续存在。成人高T2哮喘与儿童期发病相关，提示这种哮喘表型的早期起源。在儿童和成人中，高T2表型的特点是过敏原特异性IgE的过度产生（p<0.0001），并且从学龄起，在抗CD3/CD28刺激全血后IL-5的产生增加。
结论：使用易于获取的生物标记物，高T2哮喘患者可以在所有年龄段识别出不同的表型。这些患者甚至在年轻时也可能受益于生物制剂治疗。
T-high asthma phenotypes across life span
Nicole Maison, Jimmy Omony, Sabina Illi, Dominik Thiele, Chrysanthi Skevaki, Anna-Maria Dittrich, Thomas Bahmer, Klaus Friedrich Rabe, Markus Weckmann, Christine Happle, Bianca Schaub, Meike Meier, Svenja Foth, Ernst Rietschel, Harald Renz, Gesine Hansen, Matthias Volkmar Kopp, Erika von Mutius, Ruth Grychtol, ALLIANCE Study Group
Abstract
Rationale: In adults, personalised asthma treatment targets patients with T2-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.
Objectives: To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.
Methods: In the multicenter clinical ALL Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with LPS or anti-CD3/CD28.
Measurements and main results: Based on blood eosinophil counts and allergen-specific serum IgE antibodies (sIgE), patients were categorised into four mutually exclusive phenotypes: "Atopy-only", "Eosinophils-only", "T2-high" (eosinophilia+atopy) and "T2-low" (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p<0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood.
Conclusions: Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at younger age.
原理：在成人中，个性化哮喘治疗针对高T2和嗜酸性哮喘表型的患者。目前尚不清楚这种分类在儿童身上是否可行。
目的：用易于获得的生物标记物定义高T2哮喘，并比较所有年龄段的表型。
方法：在多中心临床全年龄哮喘队列（ALLIANCE）中，招募了1125名参与者（n=776名哮喘患者，n=349名对照），并随访2年（成人1年）。在基线检查和随访时，进行了广泛的临床特征分析（问卷调查、血液分类计数、过敏测试、肺功能和痰诱导（成人）。用LPS或抗CD3/CD28刺激全血后测定白细胞介素（IL）-4、IL-5和IL-13。
检测和主要结果：根据血液嗜酸性粒细胞计数和过敏原特异性血清IgE抗体（sIgE），将患者分为四种相互排斥的表型：“仅特应性”、“仅嗜酸性粒细胞”、“高T2”（嗜酸性粒细胞+特应性）和“T2低”（既不嗜酸性粒细胞也不特应性）。高T2表型存在于所有年龄段，甚至在非常年幼的儿童中，即使在随访2年后，T2高表型仍在很大程度上持续存在。成人高T2哮喘与儿童期发病相关，提示这种哮喘表型的早期起源。在儿童和成人中，高T2表型的特点是过敏原特异性IgE的过度产生（p<0.0001），并且从学龄起，在抗CD3/CD28刺激全血后IL-5的产生增加。
结论：使用易于获取的生物标记物，高T2哮喘患者可以在所有年龄段识别出不同的表型。这些患者甚至在年轻时也可能受益于生物制剂治疗。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Eur Respir J.2022 Feb 24;2102288.doi: 10.1183/13993003.02288-2021.)
(Eur Respir J.2022 Feb 24;2102288.doi: 10.1183/13993003.02288-2021.)
T-high asthma phenotypes across life span
Nicole Maison, Jimmy Omony, Sabina Illi, Dominik Thiele, Chrysanthi Skevaki, Anna-Maria Dittrich, Thomas Bahmer, Klaus Friedrich Rabe, Markus Weckmann, Christine Happle, Bianca Schaub, Meike Meier, Svenja Foth, Ernst Rietschel, Harald Renz, Gesine Hansen, Matthias Volkmar Kopp, Erika von Mutius, Ruth Grychtol, ALLIANCE Study Group
Abstract
Rationale: In adults, personalised asthma treatment targets patients with T2-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.
Objectives: To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.
Methods: In the multicenter clinical ALL Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with LPS or anti-CD3/CD28.
Measurements and main results: Based on blood eosinophil counts and allergen-specific serum IgE antibodies (sIgE), patients were categorised into four mutually exclusive phenotypes: "Atopy-only", "Eosinophils-only", "T2-high" (eosinophilia+atopy) and "T2-low" (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p<0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood.
Conclusions: Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at younger age.
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口服低剂量皮质类固醇与哮喘共患病发病率和死亡率增加相关
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新型冠状病毒肺炎时代哮喘管理和病毒传播的考虑
