A longitudinal assessment of circulating YKL-40 levels in preschool children with wheeze

Background: The chitinase-like protein YKL-40 (CHI3L1) is elevated in the circulation of adults and schoolchildren with chronic severe asthma. It is unknown whether YKL-40 is altered in younger, preschool children with wheeze, acute or chronic. We therefore examined YKL-40 in preschool children during an acute episode of wheeze and during remission, in comparison with healthy controls. Methods: Blood was obtained from 128 children (aged 6-44 months) at the emergency department during an acute episode of wheeze, and at two follow-up visits (approximately 3 months and 1 year later), as well as from 100 age-matched healthy controls on one occasion. Plasma YKL-40 levels were examined in relation to CHI3L1 rs4950928 genotype and clinical characteristics including Asthma Predictive Index, medication use, time spent with respiratory symptoms, atopic status, and blood leukocytes. Results: Children with wheeze had higher median YKL-40 levels at the acute visit (14.7 (11.5-22.6) ng/ml, p < 0.001) and 3-month follow-up (15.9 (11.5-20.2), p < 0.001) compared to the 1-year follow-up (11.9 (9.5-17.3)). YKL-40 levels in healthy controls (13.6 (11.0-17.0)) tended to be lower than those during acute wheeze (p = 0.07) and 3-month follow-up (p = 0.04), but were no different at the 1-year follow-up. CHI3L1 rs4950928 affected YKL-40 in all subjects, with highest levels present in those with the CC genotype (p < 0.001). Genotype frequency was similar in the two subject groups. YKL-40 levels showed a positive correlation with blood neutrophil counts but no consistent relationships with clinical characteristics of relevance to continuous wheeze. Conclusion: YKL-40 levels were elevated during acute wheeze in preschool children, a finding which may be related to current neutrophilic inflammation, but YKL-40 was not associated with characteristics of persistent wheeze in this young cohort.