Glucocorticoid-resistant asthma.
Glucocorticoids are currently the most effective anti-inflammatory therapy for asthma. However, a small subset of asthma sufferers do not respond to clinically relevant doses of glucocorticoids and are termed "glucocorticoid resistant." These patients are characterized by increased bronchial hyperreactivity, lower morning peak expiratory flow rates, and a longer total duration of symptoms. The definition of glucocorticoid resistance is arbitrary, and a dosage and duration of oral glucocorticoid therapy that represent a completely adequate therapeutic trial have yet to be established. For research purposes, glucocorticoid-resistant asthma is defined on the basis of a lack of improvement in airway obstruction (FEV1) following a 2-week course of oral glucocorticoid therapy. Glucocorticoid resistance is associated with in vivo and in vitro alterations in cellular responses to exogenous glucocorticoids. We have implicated abnormal regulation of the activator protein I in the molecular mechanism of glucocorticoid resistance, a phenomenon that may be confined to T cells and monocytes. The identification of an alternatively spliced isoform of the glucocorticoid receptor (GR beta) has sparked interest in the functional role of this isoform and its potential involvement in the pathology of glucocorticoid resistance. Alternative therapies for this condition will have to await a better understanding of the mechanisms of glucocorticoid action.
Loke
Tuck-Kay
TK
Department of Respiratory Medicine and Allergy, Guy's Hospital, 5th Floor, Thomas Guy House, St. Thomas Street, London SE1 9RT, UK. tkloke@doctors.org.uk
Sousa
Ana R
AR
Corrigan
Christopher J
CJ
Lee
Tak H
TH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D004351:Drug Resistance / Q000502:physiology*; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids