In The Journal of allergy and clinical immunology
BACKGROUND : Inhaled corticosteroids (CS) are a backbone of asthma treatment, improving quality of life, exacerbation rates and mortality. Though effective for most, a subset of asthma patients experience CS resistant disease despite receipt of high medication doses.
OBJECTIVE : Our goal was to investigate the transcriptomic response of bronchial epithelial cells (BEC) to inhaled corticosteroids.
METHODS : Independent component analysis was performed on datasets detailing the transcriptional response of BECs to CS treatment. The expression of these CS response components was examined in two patient cohorts and investigated in relation to clinical parameters. Supervised learning was used to predict BEC CS responses using peripheral blood gene expression.
RESULTS : We identified a signature of CS response that was closely correlated with CS use in asthma patients. Participants could be separated based on CS response genes into groups with high and low signature expression. Patients with low expression of CS-response genes, particularly those with a severe asthma diagnosis, showed worse lung function and quality of life. These individuals demonstrated enrichment for T lymphocyte infiltration in endobronchial brushings. Supervised machine learning identified a 7 gene signature from peripheral blood that reliably identified patients with poor CS response expression in BECs.
CONCLUSION : Loss of CS transcriptional responses within bronchial epithelium was related to impaired lung function and poor quality of life, particularly in severe asthma. These individuals were identified using minimally invasive blood sampling, suggesting these findings may enable earlier triage to alternative treatments.
CLINICAL IMPLICATIONS : The specific transcriptional changes in BECs and blood identified here may guide early use of additional therapies.
Ginebaugh Scott P, Hagner Matthias, Ray Anuradha, Erzurum Serpil C, Comhair Suzy A A, Denlinger Loren C, Jarjour Nizar N, Castro Mario, Woodruff Prescott G, Christenson Stephanie A, Bleecker Eugene R, Meyers Deborah A, Hastie Annette T, Moore Wendy C, Mauger David T, Israel Elliot, Levy Bruce D, Wenzel Sally E, Camiolo Matthew J
2023-Feb-14
Asthma, Corticosteroids, Systems Biology, severe asthma, transcriptomics
