Clinical trial of low-dose theophylline and montelukast in patients with poorly controlled asthma

Am J Respir Crit Care Med. 2007 Feb 1;175(3):235-42. doi: 10.1164/rccm.200603-416OC. Epub 2006 Sep 22.

Abstract

Background: Asthma treatment guidelines recommend addition of controller medications for patients with poorly controlled asthma. We compared the effectiveness of once-daily oral controller therapy with either an antileukotriene receptor antagonist (montelukast) or low-dose theophylline added to existing medications in patients with poorly controlled asthma.

Methods: We conducted a randomized, double-masked, placebo-controlled trial in 489 participants with poorly controlled asthma randomly assigned to placebo, theophylline (300 mg/d), or montelukast (10 mg/d). Participants were monitored for 24 wk to measure the rate of episodes of poor asthma control (EPACs) defined by decreased peak flow, increased beta-agonist use, increased oral corticosteroid use, or unscheduled health care visits.

Observations: There was no significant difference in EPAC rates (events/person/yr) compared with placebo: low-dose theophylline, 4.9 (95% confidence interval [CI], 3.6-6.7; not significant); montelukast, 4.0 (95% CI, 3.0-5.4; not significant); and placebo, 4.9 (95% CI, 3.8-6.4). Both montelukast and theophylline caused small improvements in prebronchodilator FEV(1) of borderline significance. Nausea was more common with theophylline only during the first 4 wk of treatment. Neither treatment improved asthma symptoms or quality of life. However, in patients not receiving inhaled corticosteroids, addition of low-dose theophylline significantly (p < 0.002) improved asthma control and symptoms as well as lung function.

Conclusions: Neither montelukast nor low-dose theophylline lowered the EPAC rate of poor asthma control in patients with poorly controlled asthma despite improved lung function. For patients not using inhaled corticosteroids, low-dose theophylline improved asthma symptom control more than montelukast or placebo, and provides a safe and low-cost alternative asthma treatment.

Publication types

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

MeSH terms

  • Acetates / administration & dosage
  • Acetates / therapeutic use*
  • Administration, Inhalation
  • Adult
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / diagnosis*
  • Asthma / drug therapy*
  • Cyclopropanes
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Flow Rates
  • Glucocorticoids / administration & dosage
  • Humans
  • Leukotriene Antagonists / administration & dosage
  • Leukotriene Antagonists / therapeutic use*
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*
  • Severity of Illness Index
  • Sulfides
  • Theophylline / administration & dosage
  • Theophylline / therapeutic use*
  • Treatment Outcome

Substances

  • Acetates
  • Anti-Asthmatic Agents
  • Cyclopropanes
  • Glucocorticoids
  • Leukotriene Antagonists
  • Quinolines
  • Sulfides
  • Theophylline
  • montelukast