中重度哮喘中过敏性，嗜酸性粒细胞和2型炎症亚型的重叠
2020/12/17
摘要
背景：目前的生物疗法针对过敏性，嗜酸性粒细胞或2型炎症表型哮喘。然而，这些亚型之间重叠的频率/程度尚不清楚。
目的：表征过敏性，嗜酸性粒细胞和2型哮喘表型之间的重叠。
方法：在两个成年人群中进行基线数据的事后分析：（a）未选择任何哮喘亚型（N=935）；（b）经过选择的过敏性哮喘（N=1049）。使用普遍接受的表型定义过敏性哮喘（皮肤点刺阳性/特异性IgE>0.35kU/L）和嗜酸性粒细胞性哮喘（血液嗜酸性粒细胞高计数≥300个细胞/μL；低截断值≥150个细胞/μL）。与以前的研究一致，选择分数呼出一氧化氮高水平≥35ppb和低截断值≥25ppb作为局部2型炎症标志物，防止与全身嗜酸性粒细胞性哮喘定义重叠。
结果：在非亚型选择人群中，78.0%患有过敏性哮喘；其中39.5%患有嗜酸性粒细胞性哮喘，29.5%患有2型哮喘。在嗜酸性粒细胞性哮喘患者中（占总数的40.6%），过敏性哮喘占75.8%，2型哮喘占41.3%。在2型哮喘患者中（占总数的28.3%），81.1%患有过敏性哮喘，59.2%患有嗜酸性粒细胞性哮喘。在过敏性哮喘选择人群中，38.3%有嗜酸性粒细胞性哮喘，29.2%有2型哮喘。在嗜酸性粒细胞性哮喘患者中，46.3%患有2型哮喘。在2型哮喘患者中，60.8%患有嗜酸性粒细胞性哮喘。在低截断值时，亚型之间的重叠增加。
结论和临床相关性：在中重度哮喘患者的事后分析中，过敏性哮喘是最常见的表型，其次是嗜酸性粒细胞和2型哮喘。尽管观察到重叠，但相当大比例的患者仅具有主要的过敏亚型。了解表型之间的重叠程度将有助于患者管理/指导治疗选择。
Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate to severe asthma
Meng Chen, Kirk Shepard 2nd, Ming Yang, Pranil Raut, Hooman Pazwash, Cecile T J Holweg, Eugene Choo
Abstract
Background: Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency/degree of overlap among these subtypes is unclear.
Objective: To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes.
Methods: Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935); (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick-positive/positive serum-specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cutoff ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cutoff of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition.
Results: In the non-subtype-selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma-selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cutoff values.
Conclusions and clinical relevance: In this post hoc analysis in adults with moderate to severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding degree of overlap across phenotypes will help patient management/guide treatment options.
背景：目前的生物疗法针对过敏性，嗜酸性粒细胞或2型炎症表型哮喘。然而，这些亚型之间重叠的频率/程度尚不清楚。
目的：表征过敏性，嗜酸性粒细胞和2型哮喘表型之间的重叠。
方法：在两个成年人群中进行基线数据的事后分析：（a）未选择任何哮喘亚型（N=935）；（b）经过选择的过敏性哮喘（N=1049）。使用普遍接受的表型定义过敏性哮喘（皮肤点刺阳性/特异性IgE>0.35kU/L）和嗜酸性粒细胞性哮喘（血液嗜酸性粒细胞高计数≥300个细胞/μL；低截断值≥150个细胞/μL）。与以前的研究一致，选择分数呼出一氧化氮高水平≥35ppb和低截断值≥25ppb作为局部2型炎症标志物，防止与全身嗜酸性粒细胞性哮喘定义重叠。
结果：在非亚型选择人群中，78.0%患有过敏性哮喘；其中39.5%患有嗜酸性粒细胞性哮喘，29.5%患有2型哮喘。在嗜酸性粒细胞性哮喘患者中（占总数的40.6%），过敏性哮喘占75.8%，2型哮喘占41.3%。在2型哮喘患者中（占总数的28.3%），81.1%患有过敏性哮喘，59.2%患有嗜酸性粒细胞性哮喘。在过敏性哮喘选择人群中，38.3%有嗜酸性粒细胞性哮喘，29.2%有2型哮喘。在嗜酸性粒细胞性哮喘患者中，46.3%患有2型哮喘。在2型哮喘患者中，60.8%患有嗜酸性粒细胞性哮喘。在低截断值时，亚型之间的重叠增加。
结论和临床相关性：在中重度哮喘患者的事后分析中，过敏性哮喘是最常见的表型，其次是嗜酸性粒细胞和2型哮喘。尽管观察到重叠，但相当大比例的患者仅具有主要的过敏亚型。了解表型之间的重叠程度将有助于患者管理/指导治疗选择。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Clin Exp Allergy. 2020 Nov 20. doi: 10.1111/cea.13790.)
(Clin Exp Allergy. 2020 Nov 20. doi: 10.1111/cea.13790.)
Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate to severe asthma
Meng Chen, Kirk Shepard 2nd, Ming Yang, Pranil Raut, Hooman Pazwash, Cecile T J Holweg, Eugene Choo
Abstract
Background: Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency/degree of overlap among these subtypes is unclear.
Objective: To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes.
Methods: Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935); (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick-positive/positive serum-specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cutoff ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cutoff of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition.
Results: In the non-subtype-selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma-selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cutoff values.
Conclusions and clinical relevance: In this post hoc analysis in adults with moderate to severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding degree of overlap across phenotypes will help patient management/guide treatment options.
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30年以上队列成人哮喘的缓解和严重程度变化
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