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

Abstract

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 < 0.05 to p < 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.