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


METHODS
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.
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy*; D003521:Cyclopropanes; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005540:Forced Expiratory Flow Rates; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013440:Sulfides; D013806:Theophylline / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D013806:Theophylline; C093875:montelukast