Benefits of Airway Androgen Receptor Expression in Human Asthma.

RATIONALE Androgens are potentially beneficial in asthma, but androgen receptor (AR) has not been studied in human airways. OBJECTIVES To measure whether AR and its ligands are associated with human asthma outcomes. METHODS We compared AR expression to lung function, symptom scores and fractional of exhaled nitric oxide (FENO) in adults enrolled in the Severe Asthma Research Program (SARP). Further, asthma exacerbations, and emergency department (ED) visits were also evaluated in the SARP, with validation studies in the Cleveland Clinic Health System (CCHS) and the National Health and Nutrition Examination Survey (NHANES). MEASUREMENTS AND MAIN RESULTS In SARP (n=128), AR gene expression from bronchoscopic epithelial brushings was positively correlated with FEV1/FVC ratio (R2=0.135, p=0.0002) and total AQLQ score (R2=0.056, p=0.016); and was negatively associated with FENO (R2=0.178, p=9.8e-06) and NOS2 gene expression (R2=0.281, p=1.2e-10). In SARP (n=1,659), CCHS (n=32,527) and NHANES (n=2,629), women had more asthma exacerbations and ED visits than men. Levels of the AR ligand precursor dehydroepiandrosterone sulfate (DHEA-S) correlated positively with FEV1 in both women and men. CONCLUSIONS Higher AR expression in bronchial epithelial cells, and higher androgen levels, are associated with better lung function, fewer symptoms and lower FENO in human asthma. The role of androgens should be considered in asthma management.