Genetic analysis of asthma distinguishes subphenotypes

About 50% of asthmatics that are genetically screened have T helper type 2 (Th2)-driven inflammation that is characterized by improved symptoms with inhaled corticosteroid response, higher IgE levels, and higher peripheral blood eosinophils.  While this genetic profiling is highly valuable by elucidating the pathogenesis of asthma and tailoring individual treatment regimens, bronchial airway epithelium brushings are invasive which limits its application to childhood asthma research.  This realization led Poole et al to determine if less invasive nasal airway epithelium brushings can proxy expression changes seen in the bronchial airway transcriptome in children with asthma (J Allergy Clin Immunol 2014, 133(3): 670-678). 

In a cohort of Puerto Rican children, the authors used whole transcriptome RNA sequencing (RNA-seq) on nasal airway brushings from 10 controls and 10 subjects with asthma and targeted RNA-seq on 50 asthmatics and 50 controls to profile 105 genes. The results were compared to established bronchial and small airway transcriptomes.  They found 90% overlap in expressed genes between the nasal and bronchial transcriptomes.  Clustering analysis identified Th2-high and Th2-low subjects differentiated by the expression of 70 genes including the Th2 cytokines IL-13 and IL-5 which were activated in Th2-high subjects. Furthermore, Th2-high subjects were more likely to have atopy, atopic asthma, high blood eosinophils, and rhinitis compared to Th2-low subjects.  

Their results indicate that nasal airway gene expression profiles largely recapitulate expression profiles in the lung and can be used to identify the Th2-high subphenotype of children with asthma.  The genetic information in nasal airway brushings can easily and effectively identify individuals with IL-13 driven asthma and a Th2-skewed systemic immune response.  Poole shows that this type of analysis identifies Th2 airway inflammation as part of the mechanistic basis of asthma in atopic individuals and it can be used to identify other genes that are dysregulated in asthma but independent of atopic status.  While larger and more diverse population studies are required, this data is valuable in both research and clinical settings. 

See below for an interview between Dr. Donald Leung, Editor-in-Chief of the Journal, and Dr. Max Seibold, one of the authors of the article: