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

Area of Science:

• Pediatric respiratory medicine
• Molecular biology
• Immunology

Background:

• Recurrent viral infections causing airway obstruction and wheezing in preschoolers are a risk factor for chronic asthma.
• Early identification of children at risk for persistent asthma is crucial for timely intervention.

Purpose of the Study:

• To investigate if gene expression profiling can identify distinct pathways in wheezing preschool children.
• To assess if gene expression data, combined with clinical information, can aid in diagnosing and predicting asthma development.

Main Methods:

• Analyzed leukocyte transcriptomes from 107 wheezing preschoolers and 66 healthy controls using RNA-sequencing.
• Applied differential expression tests, weighted correlation network analysis, and logistic regression.
• Correlated gene expression with 76 clinical traits and followed children until age 7.

Main Results:

• Enriched genes involved in innate immune responses were found in wheezing children.
• A unique acute wheeze-specific gene module correlated with early vitamin D levels and later asthma medication and lung function (FEV1%/FVC).
• A predictive model for leukotriene receptor antagonist medication at age 7 achieved high accuracy (AUC 0.815).

Conclusions:

• Blood gene expression profiles in preschool wheezers act as biomarkers, predicting asthma symptoms at school age.
• The identified gene module suggests molecular phenotyping can help differentiate children who will develop chronic asthma from those who will outgrow wheeze.