Original articles: Asthma, rhinitis, other respiratory diseasesGlucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor β-isoform☆,☆☆
Section snippets
Subjects
The study was approved by the Guy’s Hospital Ethical Committee. Nine subjects with asthma who were glucocorticoid sensitive and 6 who were glucocorticoid resistant, age and sex matched, entered into this study (Table I).
Empty Cell Glucocorticoid sensitive Glucocorticoid resistant Number 9 6 Age (y) 43 ± 4 45 ± 8 Sex 5M 3M Percent predicted FEV1 76 ± 4 71 ± 3 Percent salbutamol response* 37 ± 2 33 ± 3 Percent
Clinical findings and total numbers of inflammatory cells
The sizes of the cell-mediated reaction in glucocorticoid-sensitive and -resistant groups have previously been reported.13 In subjects with glucocorticoid-sensitive asthma, prednisolone suppressed the cutaneous induration from 25 ± 2 mm to 10 ± 1 mm (mean ± SEM) (n = 9; P < .003). In the subjects with glucocorticoid-resistant asthma the size of the cutaneous reaction did not change significantly: 13.5 ± 2 mm during placebo administration and 12 ± 1 mm (mean ± SEM) (n = 6; P = .23) after
Discussion
We demonstrate that significantly higher numbers of inflammatory cells expressing GRβ immunoreactivity were observed in the glucocorticoid–resistant tuberculin responses as compared with those in the glucocorticoid-sensitive group after placebo therapy. In contrast, no significant difference was observed in the number of cells expressing GRα immunoreactivity between the 2 groups of patients. An 8-fold higher GRα/GRβ ratio was observed in the glucocorticoid-sensitive group when compared with the
Acknowledgements
We thank Dr Christopher Corrigan for his comments.
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Supported by the Medical Research Council and the National Asthma Campaign.
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Reprint requests: Tak Lee, ScD, FRCP, Department of Respiratory Medicine and Allergy, 5th Floor Thomas Guy House, Guy’s Hospital, London SE1 9RT, United Kingdom.