Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jul 24;9(7):e102987.
doi: 10.1371/journal.pone.0102987. eCollection 2014.

Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability

Chris Newby  1 , Liam G Heaney  2 , Andrew Menzies-Gow  3 , Rob M Niven  4 , Adel Mansur  5 , Christine Bucknall  6 , Rekha Chaudhuri  7 , John Thompson  8 , Paul Burton  8 , Chris Brightling  9 ; British Thoracic Society Severe Refractory Asthma Network
Affiliations

Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability

Chris Newby et al. PLoS One. .

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: Pilot funding for the Registry was provided as unrestricted research grants from Astra Zeneca, Glaxo Smith Kline and Novartis. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1
Figure 1. Differences in clinical outcomes between baseline and follow-up for each cluster.
Pre Bronchodilator FEV1 % predicted and Blood eosinophil count statistics are Mean (+/−SD). Exacerbation frequency outcomes are median (IQR) and percentage on oral steroids are percentages.
See this image and copyright information in PMC

References

    1. Wenzel S (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18(5): 716–25. - PubMed
    1. Bousquet J, Mantzouranis E, Cruz A, Aït-Khaled N, Baena-Cagnani C, et al. (2010) Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organisation Consultation on Severe Asthma. J Allergy ClinImmunol 126(5): 926–38. - PubMed
    1. Blakey J, Wardlaw A (2012) What is severe asthma? Clin Exp Allergy 42(5): 617–62. - PubMed
    1. Brightling CE, Gupta S, Gonem S, Siddiqui S (2012) Lung damage and airway remodelling in severe asthma. Clin Exp Allergy 42(5): 638–49. - PubMed
    1. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, et al. (2008) Cluster analysis and clinical asthma phenotypes. Am J Resp Crit Care Med 178(3): 218–224. - PMC - PubMed

Publication types

MeSH terms

Substances