title: Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.
abstract: BACKGROUND
  Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies.
  
  
  OBJECTIVE
  To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma.
  
  
  METHODS
  Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy.
  
  
  RESULTS
  Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001).
  
  
  CONCLUSIONS
  Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.
authors: Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif. Electronic address: michael.x.schatz@kp.org.
authors: Michael
authors: M
authors: Schatz
authors: Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
authors: Jin-Wen Y
authors: JW
authors: Hsu
authors: Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
authors: Robert S
authors: RS
authors: Zeiger
authors: Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
authors: Wansu
authors: W
authors: Chen
authors: US Medical Affairs, Genentech Inc, South San Francisco, Calif.
authors: Alejandro
authors: A
authors: Dorenbaum
authors: Capital Allergy and Respiratory Disease Center, Sacramento, Calif.
authors: Bradley E
authors: BE
authors: Chipps
authors: US Medical Affairs, Genentech Inc, South San Francisco, Calif.
authors: Tmirah
authors: T
authors: Haselkorn
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001249:Asthma / Q000175:diagnosis* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
keywords: TENOR; atopy; cluster analysis; demographics; difficult-to-treat asthma; phenotype; severe asthma