Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability

Chris Newby, Liam G Heaney, Andrew Menzies-Gow, Rob M Niven, Adel Mansur, Christine Bucknall, Rekha Chaudhuri, John Thompson, Paul Burton, Chris Brightling

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1-11
JournalPLoS ONE
Volume9
Issue number7
DOIs
Publication statusPublished - 24 Jul 2014

Fingerprint

Cluster analysis
asthma
Refractory materials
Cluster Analysis
Registries
cluster analysis
Asthma
Phenotype
phenotype
intestinal obstruction
adrenal cortex hormones
eosinophils
air flow
Classifiers
body mass index
mouth
Eosinophils
Statistical Factor Analysis
blood
Adrenal Cortex Hormones

Keywords

  • Adolescent
  • Adrenal Cortex Hormones/therapeutic use
  • Adult
  • Anti-Asthmatic Agents/therapeutic use
  • Asthma/diagnosis
  • Body Mass Index
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Eosinophils/drug effects
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Registries
  • Severity of Illness Index
  • Societies, Medical
  • Treatment Outcome
  • United Kingdom

Cite this

Newby, Chris ; Heaney, Liam G ; Menzies-Gow, Andrew ; Niven, Rob M ; Mansur, Adel ; Bucknall, Christine ; Chaudhuri, Rekha ; Thompson, John ; Burton, Paul ; Brightling, Chris. / Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability. In: PLoS ONE. 2014 ; Vol. 9, No. 7. pp. 1-11.
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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.",
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Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability. / Newby, Chris; Heaney, Liam G; Menzies-Gow, Andrew; Niven, Rob M; Mansur, Adel; Bucknall, Christine; Chaudhuri, Rekha; Thompson, John; Burton, Paul; Brightling, Chris.

In: PLoS ONE, Vol. 9, No. 7, 24.07.2014, p. 1-11.

Research output: Contribution to journalArticle

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T1 - Statistical Cluster Analysis of the British Thoracic Society Severe Refractory Asthma Registry: Clinical Outcomes and Phenotype Stability

AU - Newby, Chris

AU - Heaney, Liam G

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AU - Niven, Rob M

AU - Mansur, Adel

AU - Bucknall, Christine

AU - Chaudhuri, Rekha

AU - Thompson, John

AU - Burton, Paul

AU - Brightling, Chris

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N2 - 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.

AB - 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.

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KW - Follow-Up Studies

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KW - Treatment Outcome

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