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Title: Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability
Authors: Newby, Chris
Heaney, L. G.
Menzies-Gow, A.
Niven, R. M.
Mansur, A.
Bucknall, C.
Chaudhuri, R.
Thompson, J.
Burton, P.
Brightling, Chris
British Thoracic Society Severe Refractory Asthma Network
First Published: 24-Jul-2014
Publisher: Public Library of Science
Citation: PLoS One, 2014, 9 (7), p. e102987
Abstract: Background: Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability. Methods: Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349). Cluster-specific outcomes were assessed after a median follow-up of 3 years. A classifier was programmed to determine cluster stability and was validated in an independent cohort of new patients recruited to the registry (n = 245). Findings: Five clusters were identified. Cluster 1 (34%) were atopic with early onset disease, cluster 2 (21%) were obese with late onset disease, cluster 3 (15%) had the least severe disease, cluster 4 (15%) were the eosinophilic with late onset disease and cluster 5 (15%) had significant fixed airflow obstruction. At follow-up, the proportion of subjects treated with oral corticosteroids increased in all groups with an increase in body mass index. Exacerbation frequency decreased significantly in clusters 1, 2 and 4 and was associated with a significant fall in the peripheral blood eosinophil count in clusters 2 and 4. Stability of cluster membership at follow-up was 52% for the whole group with stability being best in cluster 2 (71%) and worst in cluster 4 (25%). In an independent validation cohort, the classifier identified the same 5 clusters with similar patient distribution and characteristics. Interpretation: Statistical cluster analysis can identify distinct phenotypes with specific outcomes. Cluster membership can be determined using a classifier, but when treatment is optimised, cluster stability is poor.
DOI Link: 10.1371/journal.pone.0102987
ISSN: 1932-6203
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2014 Newby et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: PMCID: PMC4109965
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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