Further studies on the chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy

J Allergy Clin Immunol. 1997 Dec;100(6 Pt 1):771-4. doi: 10.1016/s0091-6749(97)70272-0.


Background: Chronotherapy studies with inhaled corticosteroids have shown optimal therapeutic benefit when steroids are administered four times per day (QID) or once daily at 3 PM.

Objective: This study evaluated whether more convenient once-daily dosage times (8 AM and 5:30 PM) produce improvement in asthma equivalent to QID.

Methods: Efficacy outcome measures included FEV1, peak expiratory flow rates, bronchial responsiveness, use of beta2-agonists, nocturnal awakenings, and responses to a quality of life questionnaire. Systemic effects were blood eosinophil count, cortisol level, 24-hour urinary cortisol, and evaluation for oral candidiasis and dysphonia.

Results: Baseline measurements for all three treatment groups were similar. For morning peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.001) and the 5:30 PM group (p = 0.003), but not the 8 AM group (p = 0.75). For evening peak expiratory flow rate, significant improvement was seen for the QID group (p = 0.005) and the 5:30 PM group (p = 0.01), but not for the 8 AM group (p = 0.47). There were significant improvements in all other outcome variables for each group except PC20. There was a significant improvement in PC20 only in the QID group. The systemic effects of the three regimens were comparable.

Conclusion: Dosing of inhaled steroid at 5:30 PM had no increased systemic effects and produced efficacy similar to QID dosing. Dosing at 8 AM did not produce results consistently comparable to QID dosing. Optimal once-daily dosing of inhaled steroid is between 3 PM and 5:30 PM.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage
  • Adult
  • Aged
  • Arousal / drug effects
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Chronotherapy / methods*
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Patient Compliance
  • Peak Expiratory Flow Rate / drug effects
  • Triamcinolone Acetonide / administration & dosage*


  • Adrenergic beta-Agonists
  • Triamcinolone Acetonide