title: Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.
abstract: Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking.
  
  
  
  Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10th/90thpercentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles.
  
  
  
  Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13.
  
  
  
  We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.
authors.affiliation: Lab of clinical immunology, Department of Microbiology and Immunology, Herestraat 49/811, 3000, Leuven, KU, Belgium. sven.seys@med.kuleuven.be.|Department of Public Health and Primary Care, Environmental Health Unit, Lab of pneumology, Leuven, KU, Belgium. sven.seys@med.kuleuven.be.
authors.forename: Sven F
authors.initials: SF
authors.lastname: Seys
authors.affiliation: Department of Public Health and Primary Care, Environmental Health Unit, Lab of pneumology, Leuven, KU, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Scheers
authors.affiliation: Respiratory department, Leuven, UZ, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Van den Brande
authors.affiliation: Lab of clinical immunology, Department of Microbiology and Immunology, Herestraat 49/811, 3000, Leuven, KU, Belgium.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Marijsse
authors.affiliation: Lab of clinical immunology, Department of Microbiology and Immunology, Herestraat 49/811, 3000, Leuven, KU, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Dilissen
authors.affiliation: Respiratory department, Leuven, UZ, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Den Bergh
authors.affiliation: Respiratory department, Leuven, UZ, Belgium.|Lab of respiratory disease, and lab of pediatric immunology, Department of Clinical and Experimental Medicine, Leuven, KU, Belgium.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Goeminne
authors.affiliation: ENT department, Leuven, UZ, Belgium.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hellings
authors.affiliation: Lab of clinical immunology, Department of Microbiology and Immunology, Herestraat 49/811, 3000, Leuven, KU, Belgium.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
authors.affiliation: Respiratory department, Leuven, UZ, Belgium.|Lab of respiratory disease, and lab of pediatric immunology, Department of Clinical and Experimental Medicine, Leuven, KU, Belgium.
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.affiliation: Paediatric department, Leuven, UZ, Belgium.|Lab of paediatric immunology, Department of Microbiology and Immunology, Leuven, KU, Belgium.
authors.forename: Dominique M A
authors.initials: DM
authors.lastname: Bullens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001530:Belgium / Q000453:epidemiology; D015415:Biomarkers; D016000:Cluster Analysis; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D013183:Sputum / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Airway inflammation; Endotype; Phenotype; Precision medicine; Type 2 inflammation