Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry

被引：78

作者：

Denton, Eve ^{[1
,2
]}

Price, David B. ^{[3
,4
,5
]}

Tran, Trung N. ^{[6
]}

Canonica, G. Walter ^{[7
,8
]}

Menzies-Gow, Andrew ^{[9
]}

FitzGerald, J. Mark ^{[10
]}

Sadatsafavi, Mohsen ^{[11
]}

Perez de Llano, Luis ^{[12
]}

Christoff, George ^{[13
]}

Quinton, Anna ^{[14
]}

Rhee, Chin Kook ^{[15
]}

Brusselle, Guy ^{[16
,17
]}

Ulrik, Charlotte ^{[18
]}

Lugogo, Njira ^{[19
]}

Hore-Lacy, Fiona ^{[1
,2
]}

Chaudhry, Isha ^{[3
]}

Bulathsinhala, Lakmini ^{[3
]}

Murray, Ruth B. ^{[3
]}

Carter, Victoria A. ^{[3
]}

Hew, Mark ^{[1
,2
]}

机构：

[1] Alfred Hlth, Allergy Asthma & Clin Immunol, Melbourne, Vic, Australia

[2] Monash Univ, Publ Hlth & Prevent Med, Melbourne, Vic, Australia

[3] Optimum Patient Care, Cambridge, England

[4] Observ & Pragmat Res Inst, Singapore, Singapore

[5] Univ Aberdeen, Ctr Acad Primary Care, Div Appl Hlth Sci, Aberdeen, Scotland

[6] AstraZeneca, Gaithersburg, MD USA

[7] Humanitas Clin & Res Ctr IRCCS, Personalized Med Asthma & Allergy, Milan, Italy

[8] Humanitas Univ, Dept Biomed Sci, Milan, Italy

[9] Royal Brompton & Harefield NHS Fdn Trust, UK Severe Asthma Network & Natl Registry, London, England

[10] Univ British Columbia, Ctr Heart Lung Hlth, Vancouver Coastal Hlth Res Inst, Vancouver, BC, Canada

[11] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada

[12] Hosp Univ Lucus Augusti, Dept Resp Med, Lugo, Spain

[13] Med Univ Sofia, Fac Publ Hlth, Sofia, Bulgaria

[14] AstraZeneca, Cambridge, England

[15] Catholic Univ Korea, Div Pulm Allergy & Crit Care Med, Dept Internal Med, Seoul St Marys Hosp,Coll Med, Seoul, South Korea

[16] Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium

[17] Erasmus MC, Dept Epidemiol & Resp Med, Rotterdam, Netherlands

[18] Hvidovre Univ Hosp, Dept Resp Med, Hvidovre, Denmark

[19] Univ Michigan, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE | 2021年 / 9卷 / 07期

关键词：

PHENOTYPES;

D O I：

10.1016/j.jaip.2021.02.059

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis. Objective: We characterized biomarker expression in adults with severe asthma. Methods: Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe, and Asia, with prespecified thresholds for biomarker positivity (serum IgE ≥ 75 kU/L, blood eosinophils ≥ 300 cells/μL, and FeNO ≥ 25 ppb), and with hierarchical cluster analysis using biomarkers as continuous variables. Results: Of 1,175 patients; 64% were female, age (mean ± SD) 53 ± 15 years, body mass index (BMI) 30 ± 8, postbronchodilator forced expiratory volume in 1 second (FEV1) predicted 72% ± 20%. By prespecified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive. There was substantial inflammatory biomarker overlap; 59% were positive for either 2 or 3 biomarkers. Five distinct clusters were identified: cluster 1 (61%, low-to-medium biomarkers) comprised highly symptomatic, older females with elevated BMI and frequent exacerbations; cluster 2 (18%, elevated eosinophils and FeNO) older females with lower BMI and frequent exacerbations; cluster 3 (14%, extremely high FeNO) older, highly symptomatic, lower BMI, and preserved lung function; cluster 4 (6%, extremely high IgE) younger, long duration of asthma, elevated BMI, and poor lung function; cluster 5 (1.2%, extremely high eosinophils) younger males with low BMI, poor lung function, and high burden of sinonasal disease and polyposis. Conclusions: There is significant overlap of biomarker positivity in severe asthma. Distinct clusters according to biomarker expression exhibit unique clinical characteristics, suggesting the occurrence of discrete patterns of underlying inflammatory pathway activation and providing pathogenic insights relevant to the era of monoclonal biologics. © 2021 The Authors

引用

页码：2680 / +

页数：16

共 29 条

[11] Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies [J].