A respiratory virus infection can be detected in all first-time wheezing children. Rhinovirus dominated the findings and was linked to atopic characteristics, prolonged cough, and parental smoking.

The data suggest diverse asthma phenotypes and mechanisms that can be predicted by using simple clinical markers at the time of the first severe wheezing episode. These findings are important for designing early intervention strategies for secondary prevention of asthma.

Children with rhinovirus‐induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus‐associated atopic or nonatopic asthma, we analyzed a cohort of 5‐year‐old children (n = 45) according to the virus etiology of the first severe wheezing episode at the mean age of 13 months and to 5‐year asthma outcome. The development of atopic asthma in children with early rhinovirus‐induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8 years.