Transcriptomic profiles of the nasal epithelium from the Genes-environments & Admixture in Latino Americans (GALA) II study
Childhood asthma is a complex disease historically defined by partially overlapping clinical features, including recurrent respiratory symptoms and reversible airway obstruction. However, the heterogeneity observed in clinical disease and airway pathology suggests that the “traditionally” defined asthma population is composed of multiple subgroups (i.e., endotypes), each with a distinct pathogenesis. Gene expression profiling of bronchial airway brushings identified the type 2-high asthma endotype, defined by excessive airway inflammation driven by type 2 cytokines, which was found in ~50% of subjects. Importantly, response to inhaled corticosteroid treatment was limited to this type 2-high endotype. The clinical utility of type 2-high asthma endotyping and the discovery of other endotypes have been limited by the need to perform an invasive bronchoscopy to obtain the bronchial brushings for analysis. Moreover, research bronchoscopies cannot be performed in children. Less invasive methods for the identification of asthma endotypes are needed. To this end, we found that the type 2-high asthma endotype can be identified by gene expression profiling of minimally invasive nasal airway epithelium brushings. Moreover, we found high nasal expression of the type 2 cytokine, IL-13,4 was associated with higher risk of asthma exacerbations among Puerto Ricans, who have the highest asthma morbidity and mortality in the U.S. Herein, we propose to use whole transcriptome sequencing of nasal airway epithelial brushings from Puerto Rican children with asthma to identify the type 2-high and other asthma endotypes, which relate to severity and drug response. Overall design: We sought to identify clinically relevant endotypes using nasal brushing samples from 695 asthmatic and healthy Puerto Rican children.