title: Elevated inflammatory markers at preschool age precede persistent wheezing at school age.
abstract: BACKGROUND
  Wheeze is a heterogeneous symptom in preschool children. At preschool age it is hard to predict whether symptoms will pass or persist and develop into asthma. Our objective is to prospectively study whether inflammatory markers in exhaled breath condensate (EBC) and pre- and post-bronchodilator interrupter resistance (Rint) assessed at preschool age, are associated with wheezing phenotypes at school age.
  
  
  METHODS
  Children (N = 230) were recruited from the Asthma DEtection and Monitoring (ADEM) study. At preschool age [mean (SE): 3.3 (0.1) yr], pre- and post-bronchodilator Rint was assessed. EBC was collected using a closed glass condenser. Inflammatory markers (IL-2, IL-4, IL-8, IL-10, sICAM) were measured using multiplex immunoassay. Wheezing phenotypes at 5 yr of age were determined based on longitudinal assessment. Children were classified as: never (N = 47), early-transient (N = 89) or persistent wheezers (N = 94).
  
  
  RESULTS
  Persistent wheezers had elevated levels of all interleukins at preschool age compared to children who never wheezed (p < 0.05). EBC markers did not differ between the persistent and transient wheezers. There was no marked difference in Rint between wheezing phenotypes.
  
  
  CONCLUSIONS
  We demonstrated that 5 yr old children with persistent wheeze already had elevated exhaled inflammatory markers at preschool age compared to never wheezers, indicating augmented airway inflammation in these children.
authors.affiliation: Department of Paediatric Pulmonology, School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands. kim.vande.kant@mumc.nl
authors.forename: Kim D G
authors.initials: KD
authors.lastname: van de Kant
authors.forename: Maria A
authors.initials: MA
authors.lastname: Jansen
authors.forename: Ester M M
authors.initials: EM
authors.lastname: Klaassen
authors.forename: Chris P
authors.initials: CP
authors.lastname: van der Grinten
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Jean W M
authors.initials: JW
authors.lastname: Muris
authors.forename: Onno C P
authors.initials: OC
authors.lastname: van Schayck
authors.forename: Quirijn
authors.initials: Q
authors.lastname: Jöbsis
authors.forename: Edward
authors.initials: E
authors.lastname: Dompeling
mesh_terms: D000403:Airway Resistance; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D045853:Exhalation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D012135:Respiratory Sounds / Q000276:immunology*; D012574:Schools; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007378:Interleukins