Comparison of the effects of two different dosing frequencies on the antiasthmatic ( left panel ) and systemic ( right panel ) responses to three graded per diem doses of budesonide (BUD) administered to 34 adults with moderate to severe unstable chronic asthma . The systemic effect of BUD was measured in terms of its impact on the 8:00 am serum cortisol level. Every patient took each of the six dose × dosing frequency combinations for the same length of time in a prospective, double-blind, balanced crossover protocol. To achieve an antiasthmatic response equivalent to that obtained with four BUD treatments per day, twice-daily treatment required a six- to sevenfold higher daily dose of BUD (arrows in left panel). This entailed a commensurate increase in the systemic toxicity of the inhaled corticosteroid (compare arrow symbols in the right panel). ANOVA = analysis of variance; PEFR = peak expiratory flow rate.