Elevated inflammatory markers at preschool age precede persistent wheezing at school age

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.