Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma

A double-blind, crossover, randomized, placebo-controlled chronotherapeutic study was designed in which eight patients (two men, 20 and 48 yr old, and six women, 22 to 58 yr old) suffering from corticosteroid-dependent allergic asthma were socially synchronized, with a diurnal activity from about 7:30 A.M. to about 11 P.M. and a nocturnal rest. During an 8 day span they were treated on a Dutimelan 8-15 regimen, labeled DTM 8-15: at 8 A.M. a pill containing 7 mg of prednisolone acetate and 4 mg of prednisolone alcohol, at 3 P.M. a pill with 15 mg of cortisone acetate and 3 mg of prednisolone alcohol, and a placebo at 8 P.M. During another 8 day span they were given a placebo at 8 A.M. and at 3 P.M. a pill with 15 mg of cortisone acetate and 3 mg of prednisolone alcohol and at 8 P.M. another pill with 7 mg of prednisolone acetate and 4 mg of prednisolone alcohol, a regimen labeled Rx 15-20. During wakefulness (between 7 A.M. and 11 P.M.), every 2 hr at eight fixed clock hours, peak expiratory flow (PEF), grip strength, and oral temperature were self-measured and dyspnea, cough, and fatigue were self-rated. The PEF 24 hr mean as well as the nocturnal dip were lower (p less than 0.05 to p less than 0.0005) with Rx 15-20 than with DTM 8-15, while the nocturnal increase of dyspnea was greater with Rx 15-20 than with DTM 8-15. Long-term administration of corticosteroids at 8 A.M. and 3 P.M. was more effective to control asthma and enhance PEF values than the same agents and dose given at 3 and 8 P.M.