title: Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.
abstract: BACKGROUND
  Cystic Fibrosis (CF) is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.
  
  
  METHODS
  The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM) algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.
  
  
  RESULTS
  Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1) a low lung health scores phenotype, 2) a younger, well-nourished, male-dominated class, 3) various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.
  
  
  CONCLUSIONS
  This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Conrad
authors.affiliation: Department of Mathematics and Statistics, San Diego State University, San Diego, California, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Bailey
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D009154:Mutation; D009752:Nutritional Status; D010641:Phenotype
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
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