According to a collaborative study by National Taiwan University and National Taiwan University Hospital, researchers found that childhood asthma is a heterogeneous disease encompassing multiple subtypes with complex pathophysiology. Dr. Yungling Lee and colleagues established transcriptomic clusters of childhood asthma using gene expression profiles of peripheral blood mononuclear cells (PBMCs) to investigate the molecular subtypes in childhood asthma, and also validated a gene signature that could identify severe asthma in two independent cohorts. This study enrolled patients from different levels of severity, ranging from mild to severe asthma under the Global Initiative for Asthma (GINA) guidelines. Based on 2048 highly variably expressed genes of PBMC among those asthmatic children, the research team applied the k-means algorithm and clustered 133 participants into three distinct asthma clusters. Asthmatic children with the highest neutrophil count among clusters showed the poorest treatment control and had unique gene expression patterns in PBMC that were associated with glucocorticoids and activation of the TH1/TH17 immune pathway. Gene expression profiling of PBMC was useful for the identification of non-TH2 severe asthma, and also implied the importance of CD8+ T cells in mediating treatment response.
The conception and design of the study was from Dr. Yungling Lee. Dr. Lee is an associate professor at the National Taiwan University College of Public Health and dedicated to genetic epidemiology and molecular epidemiology.
[Photo: Dr. Yungling L. Lee]
Dr. Yungling Lee is the corresponding author and the leader of Taiwanese Consortium of Childhood Asthma Study (TCCAS). “The study applied a novel bioinformatical method to classify asthmatic patients into 3 clusters with distinct inflammatory profiles, based on highly variably expressed genes of PBMC. PBMC and CD8+ T cells may be the promising targets not only in the investigation of asthma biology, but for subtype identification in the phenotype-based treatment of asthma.” said Dr. Lee.