COMPARISON OF 4-TIMES-A-DAY AND TWICE-A-DAY DOSING REGIMENS IN SUBJECTS REQUIRING 1200 MU-G OR LESS OF BUDESONIDE TO CONTROL MILD-TO-MODERATE ASTHMA

The aim of this study was to compare the efficacy, compliance and side -effects of budesonide administered twice daily (b.d.) and four times a day (q.d.) with a Turbuhaler(R) device in asthmatic subjects requiri ng less than or equal to 1200 mu g daily. The randomized, parallel gro up study design included a 2-week baseline period followed by a 6-12-m onth treatment period. Subjects were assessed at regular intervals in hospital through FEV(1), PC20 methacholine, adrenal function and throa t swabs. They were asked to record their symptoms and PEF values morni ng and evening at home. An asthmatic flare-up, which was the main outc ome resulting in a patient's termination of the study, was defined bef orehand as (a) 25% or greater diurnal variability in PEF for 2 consecu tive days, and/or (b) nocturnal awakenings due to asthma symptoms 2 da ys or more in the same week and/or (c) an increase (doubling or more) in the need for inhaled bronchodilator 2 days in the same week. Fifty- eight adult asthmatic subjects (20 males and 38 females) entered the s tudy, one-half being randomly assigned to the b.d. regimen and one-hal f to the q.d. regimen. Fourteen subjects were on 400 mu g, 15 subjects on 800 mu g and 29 subjects on 1200 mu g of budesonide daily. Sevente en flare-ups were recorded in the b.d. regimen group as opposed to 11 in the q.d. regimen (P=0.05), significant differences being found in t he 800 and 1200 mu g groups (a total of 13 hare-ups in the b.d. group and eight flare-ups in the q.d. group for the two doses, P=0.01). Kapl an-Meier survival analysis yielded similar results. There was no signi ficant difference in FEV(1), PC20 or cortisol levels during the study on either regimen. Throat symptoms and growth of Candida albicans were more common in the q.d. group. Compliance assessed by the number of t imes the Turbuhaler(R) device was actuated was significantly better in the b.d. group (95%) as compared with the q.d. group (83%). To conclu de, administering inhaled budesonide with a Turbuhaler(R) device on a q.d. basis results in fewer flare-ups in spite of less satisfactory co mpliance and more common, local side-effects than on a b.d. regimen at daily doses of 800 and 1200 mu g.