Decreased Glucocorticoid Binding Affinity to Glucocorticoid Receptor Is Important in the Poor Response to Steroid Therapy of Older-Aged Patients with Severe Bronchial Asthma

Abstract

The aim of this study was to determine whether alterations in glucocorticoid (GC) to GC receptor (GC/GCR) binding affinity and the state of airway remodeling contribute to the poor response to GC therapy of severe bronchial asthma patients in old age. Peripheral blood mononuclear cells were obtained from two groups with severe asthma, 10 patients with steroid resistant (SR), 7 patients with steroid sensitive (SS), and 6 normal controls. GC/GCR binding affinity for dexamethasone was determined by using a radioligand binding assay with Scatchard analysis, and bronchial wall thickness in high-resolution computed tomography was used to determine the degree of airway remodeling. SR patients had decreased GC/GCR binding affinity (Kd = 24.3 ± 9.55; p < 0.05) compared with the SS patients (Kd = 13.5 ± 1.48; p < 0.05) and the normal controls (Kd = 4.24 ± 1.09). The inner diameter of bronchi and the thickness of the bronchial wall of segmental and subsegmental bronchi were increased significantly in patients compared with normal controls. However, no significant differences were found between the SR and SS patients. Our results suggest that decreased GC/GCR binding affinity may be an important factor of clinical GC resistance in the acute exacerbation of chronic severe asthma in older-aged bronchial asthma patients.