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

Charles G. Irvin, David A. Kaminsky, Nicholas R. Anthonisen, Mario Castro, Nicola A. Hanania, Janet T. Holbrook, John J. Lima, Robert A. Wise

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


Background: Asthma treatment guidelines recommend addition of controller medications for patients with poorly controlled asthma. Wecompared 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 β-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 FEV1 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.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number3
StatePublished - Feb 1 2007


  • Antiasthmatic agents
  • Bronchodilator agents
  • Clinical trial
  • Multicenter studies

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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