Cutaneous vasoconstrictor response to glucocorticoids in asthma.
The aim of the study was to find out whether asthma patients whose airways obstruction is sensitive (CS) or resistant (CR) to corticosteroid treatment also differ in their cutaneous vasoconstrictor response to a potent topical glucocorticoid. Corticosteroid resistance was defined by failure of forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate to improve by at least 15% after a 2-week trial of corticosteroids (prednisolone 20 mg daily for 1 week, then 40 mg daily for 1 week) despite more than 15% improvement with inhaled beta agonists. Beclomethasone dipropionate in concentrations of 3 micrograms/ml, 10 micrograms/ml, 30 micrograms/ml, and 100 micrograms/ml was applied to forearm skin; the site was occluded under plastic and the degree of blanching assessed after 18 h. CS asthmatic subjects (n = 31), asthma patients with mild airways obstruction (n = 26), asthma patients taking long-term prednisolone (n = 13), and healthy volunteers showed similar vasoconstrictor responses. In CR asthmatic subjects (n = 15), the response (expressed in terms of either blanching intensity or the proportion of patients showing a positive response) was significantly lower than that in the CS group at concentrations of 3 micrograms/ml (p less than 0.01), 10 micrograms/ml (p less than 0.01), and 30 micrograms/ml (p less than 0.05), but not at 100 micrograms/ml. This resistance to glucocorticoids in the skin, together with reported evidence of glucocorticoid resistance in peripheral blood leucocytes, suggests a general defect in the ability of tissues to respond to glucocorticoids in CR asthma.
Brown
P H
PH
Department of Medicine, Northern and Western General Hospitals, Edinburgh, UK.
Teelucksingh
S
S
Matusiewicz
S P
SP
Greening
A P
AP
Crompton
G K
GK
Edwards
C R
CR
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019819:Budesonide; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012867:Skin / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide; D011239:Prednisolone; D001507:Beclomethasone