Circadian rhythm in peak expiratory flow: alteration with nocturnal asthma and theophylline chronotherapy

Chronobiol Int. 2000 Jul;17(4):513-9. doi: 10.1081/cbi-100101061.


We investigated changes in the circadian rhythm of peak expiratory flow (PEF) in seven persons with nocturnal asthma for a 24h span when (1) they were symptom free and their disease was stable, (2) their asthma deteriorated and nocturnal symptoms were frequent, and (3) they were treated with theophylline chronotherapy. Subjects recorded their PEF every 4h between 07:00 and 23:00 one day each period. Circadian rhythms in PEF were assessed using the group-mean cosinor method. The circadian rhythm in PEF varied according to asthma severity. Significant circadian rhythms in PEF were detected during the period when asthma was stable and when it was unstable and nocturnal symptoms were frequent. When nocturnal symptoms were present, the bathyphase (trough time) of the PEF rhythm narrowed to around 04:00; during this time of unstable asthma, the amplitude of the PEF pattern increased 3.9-fold compared to the symptom-free peiiod. No significant group circadian rhythm was detected during theophylline chronotherapy. Evening theophylline chronotherapy proved to be prophylactic for persons whose symptoms before treatment had occurred between midnight and early morning. Changes in the characteristics of the circadian rhythm of PEF, particularly amplitude and time of bathyphase, proved useful in determining when to institute theophylline chronotherapy to avert nocturnal asthma symptoms.

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy*
  • Asthma / physiopathology*
  • Bronchodilator Agents / administration & dosage*
  • Chronotherapy*
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peak Expiratory Flow Rate / drug effects
  • Peak Expiratory Flow Rate / physiology*
  • Theophylline / administration & dosage*


  • Bronchodilator Agents
  • Theophylline