title: Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study.
abstract: BACKGROUND
  Many patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results.
  
  
  METHODS
  We performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy.
  
  
  RESULTS
  Analyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: -17.3-69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77-21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups.
  
  
  CONCLUSIONS
  Our study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration.
authors.affiliation: University of Ottawa, Division of Respirology, Ottawa, ON, Canada. nvoduc@toh.on.ca
authors.forename: Nha
authors.initials: N
authors.lastname: Voduc
authors.forename: Gonzalo G
authors.initials: GG
authors.lastname: Alvarez
authors.forename: Kayvan
authors.initials: K
authors.lastname: Amjadi
authors.forename: Caroline
authors.initials: C
authors.lastname: Tessier
authors.forename: Elham
authors.initials: E
authors.lastname: Sabri
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Aaron
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D005082:Physical Exertion / Q000187:drug effects*; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests / Q000379:methods; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects; D013995:Time; D016896:Treatment Outcome
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D013806:Theophylline