title: Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability.
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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom; Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
authors: Chris
authors: C
authors: Newby
authors: Centre for Infection and Immunity, Queen's University of Belfast, Belfast, United Kingdom.
authors: Liam G
authors: LG
authors: Heaney
authors: Royal Brompton Hospital, London, United Kingdom.
authors: Andrew
authors: A
authors: Menzies-Gow
authors: North West Lung Centre, University of Manchester, Manchester, United Kingdom.
authors: Rob M
authors: RM
authors: Niven
authors: Severe and Brittle Asthma Unit, Birmingham Heartlands Hospital, Birmingham, United Kingdom.
authors: Adel
authors: A
authors: Mansur
authors: Department of Respiratory Medicine, Stobhill Hospital, Glasgow, United Kingdom.
authors: Christine
authors: C
authors: Bucknall
authors: Department of Respiratory Medicine, Division of Immunology, Infection and Inflammation, University of Glasgow and Gartnavel General, Glasgow, United Kingdom.
authors: Rekha
authors: R
authors: Chaudhuri
authors: Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
authors: John
authors: J
authors: Thompson
authors: Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
authors: Paul
authors: P
authors: Burton
authors: Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
authors: Chris
authors: C
authors: Brightling
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012042:Registries; D012720:Severity of Illness Index; D012955:Societies, Medical; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents