Trial of cyclosporin in corticosteroid-dependent chronic severe asthma.
The treatment of chronic severe asthma is unsatisfactory for many patients. In a randomised, double-blind, placebo-controlled, crossover trial we have tested whether cyclosporin, which is thought to act primarily by inhibition of T lymphocyte activation, improves lung function in corticosteroid-dependent asthmatics. After a 4-week run-in period, 33 patients with longstanding asthma (mean duration 27 years), and who had required continuous oral corticosteroids for a mean of 9.3 years, were randomised to receive either cyclosporin (initial dose 5 mg/kg per day) or placebo for 12 weeks, crossing over after a 2-week washout period. Mean baseline forced expiratory volume in 1 s (FEV1) was 60.1% of the predicted value. 2 patients failed to complete the protocol and 1 withdrew because of hypertrichosis. Cyclosporin therapy resulted in a mean increase above placebo of 12.0% in morning peak expiratory flow rate (PEFR; p less than 0.004) and 17.6% in FEV1 (p less than 0.001). The frequency of disease exacerbations requiring an increased prednisolone dose was reduced by 48% in patients on cyclosporin compared with placebo (p less than 0.02). Diurnal variation in PEFR decreased by a mean of 27.6% (p = 0.04). Cyclosporin for 12 weeks was well tolerated by this group of chronic asthmatics, in whom the mean whole-blood trough concentration was 152 micrograms/l. These findings provide further evidence of a role for activated T lymphocytes in the pathogenesis of asthma. Specific pharmacological targeting of this cell could form the basis of a novel approach to the treatment of asthma.
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.
A G
AG
Alexander
N C
NC
Barnes
A B
AB
Kay
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011239:Prednisolone / Q000627:therapeutic use
D016572:Cyclosporine; D011239:Prednisolone