Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication

Background Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and recognised as a risk factor for the development of chronic asthma. We aimed at analyaing whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development.

Methods We analyaed leukocyte transcriptomes from preschool children (6 months–3 y) at acute wheeze (n=107), and at a revisit 2–3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were clinically followed until age 7 years. Differential expression tests, weighted correlation network analysis (WGCNA) and logistic regression were applied and correlations to 76 clinical traits evaluated.

Findings Significant enrichment of genes involved in the innate immune responses were observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, that was associated with Vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC several years later, at age 7 (p<0.005). A model that predicts LTRA-medication at 7 years of age with high accuracy was developed (AUC=0.815, 95% CI: 0.668–0.962).

Interpretation Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school-age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children that will outgrow their wheeze from those that will develop chronic asthma.