重度哮喘的多病共存表型及其相关特征：一项基于欧洲重度哮喘登记资料的观察性研究
2026/03/30
摘要
背景：目前重度哮喘中多病共存的表型特征尚未明确。本研究旨在通过识别和表征共病的聚集模式，界定欧洲重度哮喘患者的多病共存表型及其特征。
方法：本研究分析了“泛欧洲重度异质性哮喘研究协作计划：以患者为中心”（SHARP）中央数据库中各国重度哮喘登记资料的横断面数据。根据欧洲四个地理区域（北、南、东、西）对患者进行分组。采用层级聚类分析方法，对这些区域内最常见的10种共病的相关结构进行表征，并进一步定义多病共存表型及其临床特征。
结果：研究纳入了来自11个国家的2690例重度哮喘患者，涵盖23种共病。在欧洲四个区域中，一致观察到三个共病簇：1）骨质疏松合并类固醇相关体重增加，2）湿疹合并鼻炎，3）慢性鼻窦炎合并鼻息肉。此外，四种共病（肥胖、支气管扩张、胃食管反流、心理因素）在不同区域间的聚类模式表现不一。多病共存在重度哮喘中普遍存在。根据共病簇归属，将患者划分为不同的多病共存表型(MMP)。其中，MMP sn（鼻-鼻窦相关型）和MMP u（无特定聚类归属型）最为常见。MMP ster（类固醇相关多病共存型）患者维持性口服糖皮质激素（m-OCS）使用水平和BMI最高，且肺功能最差、哮喘控制不佳、急性加重更为频繁。MMP max（最大多病共存型）则表现为多种共病的高流行率，且对m-OCS和生物制剂治疗的需求更高。
结论：多病共存在重度哮喘中十分普遍，并可划分为具有特征性临床表现和预后的、可重复识别的新型表型。识别这些表型有助于实现对重度哮喘患者的整体管理。未来临床指南应促进对此类表型的认识，以支持更有效的哮喘个体化诊疗。
资助：欧洲呼吸学会（ERS）及制药行业合作伙伴（赛诺菲、TEVA、诺华、葛兰素史克、凯西）。
关键词：聚类；多病共存；表型；重度哮喘。
Abstract
Background:The phenotypic nature of multimorbidity in severe asthma is poorly understood. Our aims in this study were to define multimorbidity phenotypes and their characteristics in severe asthma across Europe by identifying and characterising co-aggregation of comorbidities.
Methods:Cross-sectional patient data were analysed from the pan-European Severe Heterogenous Asthma Research Collaboration: Patient Centred (SHARP) Central database of national severe asthma registries. Patients were grouped by four European regions (North, South, East, and West). Hierarchical clustering of comorbidities was applied to characterise the correlation structure of the ten commonest comorbidities within these geographical regions. Subsequent multimorbidity phenotypes (MMP) and their clinical features were then defined.
Findings:Data were available for 2690 severe asthma patients and 23 comorbidities from 11 countries. Three comorbidity clusters were consistently seen across the four European regions: 1) osteoporosis plus steroid-induced weight gain, 2) eczema plus rhinitis, and 3) chronic sinusitis plus nasal polyps. Four further comorbidities (obesity, bronchiectasis, gastro-oesophageal reflux disease, psychological factors) showed variable clustering. Multimorbidity was ubiquitous. Patients were assigned multimorbidity phenotypes (MMP) according to comorbidity cluster alignment. MMP sn (sinonasal-associated) and MMP u (no specific cluster alignment) were commonest. MMP ster (steroid-associated multimorbidity) had highest maintenance oral steroid (m-OCS) use, and Body Mass Index, plus worst lung function, asthma control, and asthma exacerbation frequency. MMP max (maximal multimorbidity) showed high prevalence of variably assigned comorbidities, higher m-OCS and biologic treatment needs.
Interpretation:Multimorbidity is common in severe asthma and can be classified into replicable novel phenotypes with characteristic clinical traits and outcomes. Recognising these phenotypes can guide better care of the 'whole patient' with severe asthma. Future clinical guidance should promote such understanding in order to support delivery of more effective personalised asthma care.
Funding:European Respiratory Society, pharmaceutical industry partners (Sanofi, TEVA, Novartis, GlaxoSmithKline, Chiesi).
Keywords: Cluster; Multimorbidity; Phenotype; Severe asthma.
背景：目前重度哮喘中多病共存的表型特征尚未明确。本研究旨在通过识别和表征共病的聚集模式，界定欧洲重度哮喘患者的多病共存表型及其特征。
方法：本研究分析了“泛欧洲重度异质性哮喘研究协作计划：以患者为中心”（SHARP）中央数据库中各国重度哮喘登记资料的横断面数据。根据欧洲四个地理区域（北、南、东、西）对患者进行分组。采用层级聚类分析方法，对这些区域内最常见的10种共病的相关结构进行表征，并进一步定义多病共存表型及其临床特征。
结果：研究纳入了来自11个国家的2690例重度哮喘患者，涵盖23种共病。在欧洲四个区域中，一致观察到三个共病簇：1）骨质疏松合并类固醇相关体重增加，2）湿疹合并鼻炎，3）慢性鼻窦炎合并鼻息肉。此外，四种共病（肥胖、支气管扩张、胃食管反流、心理因素）在不同区域间的聚类模式表现不一。多病共存在重度哮喘中普遍存在。根据共病簇归属，将患者划分为不同的多病共存表型(MMP)。其中，MMP sn（鼻-鼻窦相关型）和MMP u（无特定聚类归属型）最为常见。MMP ster（类固醇相关多病共存型）患者维持性口服糖皮质激素（m-OCS）使用水平和BMI最高，且肺功能最差、哮喘控制不佳、急性加重更为频繁。MMP max（最大多病共存型）则表现为多种共病的高流行率，且对m-OCS和生物制剂治疗的需求更高。
结论：多病共存在重度哮喘中十分普遍，并可划分为具有特征性临床表现和预后的、可重复识别的新型表型。识别这些表型有助于实现对重度哮喘患者的整体管理。未来临床指南应促进对此类表型的认识，以支持更有效的哮喘个体化诊疗。
资助：欧洲呼吸学会（ERS）及制药行业合作伙伴（赛诺菲、TEVA、诺华、葛兰素史克、凯西）。
关键词：聚类；多病共存；表型；重度哮喘。
（南方医科大学南方医院 陈垚欣 彭晓阡 赵海金）
(Freeman A, Rink S, Bansal AT, et al. Multimorbidity phenotypes and associated characteristics in severe asthma: an observational study of European severe asthma registries. Lancet Reg Health Eur. 2026;63:101600. Published 2026 Feb 5. doi:10.1016/j.lanepe.2026.101600)
(Freeman A, Rink S, Bansal AT, et al. Multimorbidity phenotypes and associated characteristics in severe asthma: an observational study of European severe asthma registries. Lancet Reg Health Eur. 2026;63:101600. Published 2026 Feb 5. doi:10.1016/j.lanepe.2026.101600)
Abstract
Background:The phenotypic nature of multimorbidity in severe asthma is poorly understood. Our aims in this study were to define multimorbidity phenotypes and their characteristics in severe asthma across Europe by identifying and characterising co-aggregation of comorbidities.
Methods:Cross-sectional patient data were analysed from the pan-European Severe Heterogenous Asthma Research Collaboration: Patient Centred (SHARP) Central database of national severe asthma registries. Patients were grouped by four European regions (North, South, East, and West). Hierarchical clustering of comorbidities was applied to characterise the correlation structure of the ten commonest comorbidities within these geographical regions. Subsequent multimorbidity phenotypes (MMP) and their clinical features were then defined.
Findings:Data were available for 2690 severe asthma patients and 23 comorbidities from 11 countries. Three comorbidity clusters were consistently seen across the four European regions: 1) osteoporosis plus steroid-induced weight gain, 2) eczema plus rhinitis, and 3) chronic sinusitis plus nasal polyps. Four further comorbidities (obesity, bronchiectasis, gastro-oesophageal reflux disease, psychological factors) showed variable clustering. Multimorbidity was ubiquitous. Patients were assigned multimorbidity phenotypes (MMP) according to comorbidity cluster alignment. MMP sn (sinonasal-associated) and MMP u (no specific cluster alignment) were commonest. MMP ster (steroid-associated multimorbidity) had highest maintenance oral steroid (m-OCS) use, and Body Mass Index, plus worst lung function, asthma control, and asthma exacerbation frequency. MMP max (maximal multimorbidity) showed high prevalence of variably assigned comorbidities, higher m-OCS and biologic treatment needs.
Interpretation:Multimorbidity is common in severe asthma and can be classified into replicable novel phenotypes with characteristic clinical traits and outcomes. Recognising these phenotypes can guide better care of the 'whole patient' with severe asthma. Future clinical guidance should promote such understanding in order to support delivery of more effective personalised asthma care.
Funding:European Respiratory Society, pharmaceutical industry partners (Sanofi, TEVA, Novartis, GlaxoSmithKline, Chiesi).
Keywords: Cluster; Multimorbidity; Phenotype; Severe asthma.
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