Cluster analysis of inflammatory biomarker expression in the International Severe Asthma Registry (ISAR)

Eve Denton* (Corresponding Author), David B Price, Trung N Tran, G Walter Canonica, Andrew Menzies-Gow, J Mark FitzGerald, Mohsen Sadatsafavi, Luis Perez de Llano, George Christoff, Anna Quinton, Chin Kook Rhee, Guy Brusselle, Charlotte Ulrik, Njira Lugogo, Fiona Hore-Lacy, Isha Chaudhry, Lakmini Bulathsinhala, Ruth B Murray, Victoria A Carter, Mark Hew

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
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Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis. We aimed to characterize biomarker expression in adults with severe asthma.
Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe and Asia, with pre-specified thresholds for biomarker positivity (serum IgE ³75kU/L, blood eosinophils ³300 cells/uL, FeNO ³25ppb), and with hierarchical cluster analysis using biomarkers as continuous variables.
Of 1,175 patients; 64% were female, age (mean ±SD) 53±15 years, body mass index (BMI) 30±8, post-bronchodilator FEV 1 predicted 74±20%. By pre-specified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive.
Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation There was substantial overlap; 59% were positive for either two or three 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 sino-nasal disease and polyposis.
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.
Original languageEnglish
Pages (from-to)2680-2688.e7
Number of pages16
JournalThe Journal of Allergy and Clinical Immunology: In Practice
Issue number7
Early online date18 Mar 2021
Publication statusPublished - Jul 2021


  • Severe asthma
  • Biomarkers
  • Immunoglobulin E
  • Fractional exhaled nitric oxide
  • Eosinophils


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