title: 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.
authors: Department of Internal Medicine, Ewha Womans Medical Research Center, Ewha Womans University College of Medicine, Seoul, Korea.
authors: Young Joo
authors: YJ
authors: Cho
authors: Kyung Eun
authors: KE
authors: Lee
authors: Kyeung En
authors: KE
authors: Lee
mesh_terms: D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D008776:Methylprednisolone Hemisuccinate; D003907:Dexamethasone