title: Sputum cytokine mapping reveals an 'IL-5, IL-17A, IL-25-high' pattern associated with poorly controlled asthma.
abstract: OBJECTIVE
  Asthma is a heterogeneous disease with various clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA expression patterns in an unselected group of adult asthma patients to characterize the underlying inflammatory process.
  
  
  METHODS
  Differential cell counts and cytokine mRNA (quantified by real-time PCR) were analysed on sputum from 40 controls and 66 asthmatic adults. A 'cytokine-high' profile was defined if mRNA levels for that particular cytokine exceeded the 90th percentile value in the control population. Radar graphs were used to visualize cytokine profiles.
  
  
  RESULTS
  Sputum mRNA analysis confirmed heterogeneity of cytokine patterns among patients. Thirty-six patients (55%) had a Th2 cytokine pattern: 'IL-5-high' (n = 13), 'IL-4-high' (n = 17) or 'IL-4- and IL-5-high' (n = 6). The 'IL-5-high' asthma profile (n = 13) coincided with the 'IL-25-high' (10/13) and surprisingly also with the 'IL-17A-high' (11/13) profile. The 'IL-5-/IL-25-/IL-17A-high profile was different from the 'IL-4-high' pattern. Patients with the 'IL-5, IL-17A, IL-25-high' pattern had significantly worse lung function parameters. Uncontrolled asthmatics [Asthma Control Test (ACT) < 20] had higher sputum IL-5, IL-17A and IL-25 mRNA levels compared to controlled asthmatics (P = 0.002; P = 0.002; P = 0.066) and uncontrolled asthma is more common among 'IL-5- and IL-17A-high' asthmatics compared to 'IL-5-, IL-17A-low' asthmatics (χ(2) = 3.7, P = 0.027; relative risk (RR): 1.8, 95% CI = 1.1-3.1).
  
  
  CONCLUSIONS
  Patients with the 'IL-5, IL-17A, IL-25-high' airway inflammatory pattern are often uncontrolled asthmatics, despite daily treatment. It seems worthwhile to evaluate whether measuring sputum cytokine levels might be used to assess the response to increased doses of steroids in patients with asthma.
authors: Pneumology, Department of Clinical and Experimental Medicine, Catholic University of Leuven (KU Leuven), Leuven, Belgium.
authors: S F
authors: SF
authors: Seys
authors: M
authors: M
authors: Grabowski
authors: W
authors: W
authors: Adriaensen
authors: A
authors: A
authors: Decraene
authors: E
authors: E
authors: Dilissen
authors: J A
authors: JA
authors: Vanoirbeek
authors: L J
authors: LJ
authors: Dupont
authors: J L
authors: JL
authors: Ceuppens
authors: D M A
authors: DM
authors: Bullens
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013183:Sputum / Q000737:chemistry* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016207:Cytokines; C486701:IL25 protein, human; D020381:Interleukin-17; D015848:Interleukin-5
keywords: airway inflammation; asthma control; asthma phenotyping; cytokine; induced sputum