Controlled-release theophylline inhibits early morning airway obstruction and hyperresponsiveness in asthmatic subjects

Ann Allergy Asthma Immunol. 1996 Aug;77(2):106-10. doi: 10.1016/s1081-1206(10)63495-3.

Abstract

Background: Nocturnal asthma reflects the severity of the disease, and thus its pharmacologic prevention represents one on the main goals of asthma management.

Subjects and methods: To determine whether controlled-release theophylline inhibits the development of airway obstruction and/or airway hyperresponsiveness early in the morning, we examined 18 subjects reporting recurrent nocturnal asthma. In each subject, after five days' treatment with an 8 PM increasing dose of oral controlled-release theophylline, up to 10 +/- 1 mg/kg or placebo the night before the study day, we measured serum theophylline, FEV1 and PC20FEV1 at 6 AM, 2 PM and 10 PM.

Results: At 6 AM, both FEV1 and PC20FEV1 were significantly higher on theophylline than on placebo (3.52 +/- 0.22 versus 3.17 +/- 0.25 L; P < .005 and 2.76 divided by 3.61 versus 1.55 divided by 3.73 mg/mL; P < .05, respectively). At 2 PM and 10 PM FEV1, but not PC20FEV1, was higher on theophylline than on placebo (3.73 +/- 0.21 versus 3.54 +/- 0.25 L; P < .05 and 3.40 +/- 0.22 versus 3.24 +/- 0.24 L; P < .05). Serum theophylline was 12.8 +/- 1.1 micrograms/ml, 8.9 +/- 0.77 and 9.5 +/- 0.85 at 6 AM, 2 PM and 10 PM, respectively.

Conclusions: We conclude that an evening dose of controlled-release theophyl line inhibits early morning airway obstruction and hyperresponsiveness, and that it may be helpful in the prevention of nocturnal asthma.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adult
  • Airway Obstruction / complications
  • Airway Obstruction / prevention & control*
  • Asthma / complications
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Circadian Rhythm
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Headache / chemically induced
  • Humans
  • Male
  • Methacholine Chloride / administration & dosage
  • Methacholine Chloride / pharmacology
  • Middle Aged
  • Nausea / chemically induced
  • Theophylline / administration & dosage*
  • Theophylline / adverse effects
  • Theophylline / blood
  • Tremor / chemically induced

Substances

  • Delayed-Action Preparations
  • Methacholine Chloride
  • Theophylline