哮喘的多维评估确定临床相关表型重叠：一项横断面研究
2020/09/18
摘要
背景：哮喘是一种具有多种表型的异质性疾病，但表型重叠的相关性仍有待进一步研究。
目的：探讨表型重叠与哮喘临床及炎症特征的关系。
方法：在这项横断面研究中，对522例稳定的哮喘成年患者进行多维评估。确定了10种最常见的哮喘表型，然后将其分为与T2型或非T2型炎症相关的表型。此外，表型重叠评分（POS），代表累积的伴随表型，被用来分析其与临床和炎症哮喘的关系。
结果：522名受试者中，73.4%（n=383）存在表型重叠，47.5%（n=248）的T2和非T2混合炎症并存。T2阳性与嗜酸性粒细胞、IgE、FeNO呈正相关，与AQLQ、痰中性粒细胞、IL-17A、IL-8、TNF-α呈负相关。非T2阳性与ACQ、中性粒细胞、痰液IL-8呈正相关，与AQLQ、FEV1、血嗜酸性粒细胞、IgE、FeNO呈负相关（均P<0.05）。与T2和非T2混合炎症相关的表型患者T2炎症生物标志物升高，但哮喘控制较差。T2（校正β=-0.191，P=0.035）和非T2（校正β=0.310，P<0.001）POSs均与急性加重显著相关。
结论：表型重叠在哮喘患者中极为常见，并与临床和炎症特征显著相关。与混合性T2和非T2炎症相关的表型患者可能由于非T2炎症增加而对药物无反应。多维哮喘评估确定临床相关表型重叠。
Multidimensional assessment of asthma identifies clinically relevant phenotype overlap: a cross-sectional study
Yu Yu Han, Xin Zhang, Ji Wang, Gang Wang, Brian G Oliver, Hong Ping Zhang, De Ying Kang, Lei Wang, Zhi Xin Qiu, Wei Min Li, Gang Wang
Abstract
Background: Asthma is a heterogenous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored.
Objective: To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma.
Methods: In this cross-sectional study, adult participants with stable asthma (n=522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles.
Results: Among the 522 participants, 73.4% (n=383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n=248). T2 POS was positively associated with eosinophils, IgE, and FeNO, and negatively with AQLQ, sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with ACQ, neutrophils and sputum IL-8, and negatively with AQLQ, FEV1, blood eosinophils, IgE, and FeNO (all P<0.05). Patients with phenotypes that are associated with mixed T2 and non-T2 inflammation had elevated T2 inflammation biomarkers but worse asthma control. Both T2 (adjusted β = -0.191, P=0.035) and non-T2 (adjusted β = 0.310, P<0.001) POSs were significantly associated with severe exacerbations.
Conclusions: Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap.
背景：哮喘是一种具有多种表型的异质性疾病，但表型重叠的相关性仍有待进一步研究。
目的：探讨表型重叠与哮喘临床及炎症特征的关系。
方法：在这项横断面研究中，对522例稳定的哮喘成年患者进行多维评估。确定了10种最常见的哮喘表型，然后将其分为与T2型或非T2型炎症相关的表型。此外，表型重叠评分（POS），代表累积的伴随表型，被用来分析其与临床和炎症哮喘的关系。
结果：522名受试者中，73.4%（n=383）存在表型重叠，47.5%（n=248）的T2和非T2混合炎症并存。T2阳性与嗜酸性粒细胞、IgE、FeNO呈正相关，与AQLQ、痰中性粒细胞、IL-17A、IL-8、TNF-α呈负相关。非T2阳性与ACQ、中性粒细胞、痰液IL-8呈正相关，与AQLQ、FEV1、血嗜酸性粒细胞、IgE、FeNO呈负相关（均P<0.05）。与T2和非T2混合炎症相关的表型患者T2炎症生物标志物升高，但哮喘控制较差。T2（校正β=-0.191，P=0.035）和非T2（校正β=0.310，P<0.001）POSs均与急性加重显著相关。
结论：表型重叠在哮喘患者中极为常见，并与临床和炎症特征显著相关。与混合性T2和非T2炎症相关的表型患者可能由于非T2炎症增加而对药物无反应。多维哮喘评估确定临床相关表型重叠。
(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)
(J Allergy Clin Immunol Pract. 2020 Aug 10;S2213-2198(20)30806-0. doi: 10.1016/j.jaip.2020.07.048.)
(J Allergy Clin Immunol Pract. 2020 Aug 10;S2213-2198(20)30806-0. doi: 10.1016/j.jaip.2020.07.048.)
Multidimensional assessment of asthma identifies clinically relevant phenotype overlap: a cross-sectional study
Yu Yu Han, Xin Zhang, Ji Wang, Gang Wang, Brian G Oliver, Hong Ping Zhang, De Ying Kang, Lei Wang, Zhi Xin Qiu, Wei Min Li, Gang Wang
Abstract
Background: Asthma is a heterogenous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored.
Objective: To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma.
Methods: In this cross-sectional study, adult participants with stable asthma (n=522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles.
Results: Among the 522 participants, 73.4% (n=383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n=248). T2 POS was positively associated with eosinophils, IgE, and FeNO, and negatively with AQLQ, sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with ACQ, neutrophils and sputum IL-8, and negatively with AQLQ, FEV1, blood eosinophils, IgE, and FeNO (all P<0.05). Patients with phenotypes that are associated with mixed T2 and non-T2 inflammation had elevated T2 inflammation biomarkers but worse asthma control. Both T2 (adjusted β = -0.191, P=0.035) and non-T2 (adjusted β = 0.310, P<0.001) POSs were significantly associated with severe exacerbations.
Conclusions: Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap.
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应用糖皮质激素毒性指数量化严重哮喘患者的糖皮质激素相关并发症率
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儿童期哮喘的独特免疫表型
