Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma

Respir Med. 2002 May;96(5):322-9. doi: 10.1053/rmed.2002.1282.


The objective of this study was to compare the efficacy and safety of the second controller medications (long-acting beta2-agonist, leukotriene receptor antagonist and sustained-release theophylline) used in addition to inhaler corticosteroid treatment in moderate persistent asthma. A total of 64 patients with asthma, in the moderate persistent asthma category, were divided into three groups. Patients, all of whom were concurrently using inhaled corticosteroid (Budesonide 400 microg twice daily), were treated for 3 months with either inhaled formoterol 9 microg twice daily (first group), oral zafirlukast 20 mg twice daily (second group), or sustained-release theophylline 400 mg once daily (third group). All of the patients were subjected to assessments on the subject of peak expiratory flow (PEF) variability, forced expiratory volume in 1 sec (FEV1), asthma symptom scores (daytime and night-time), supplemental terbutalin use, asthma exacerbations and adverse events. Over the 3-month treatment period. In all of the three groups, significant improvements were recorded in the lung function, asthma symptom scores and supplemental terbutalin use criteria, as a result oftreatments applied. Formoterol treatment resulted in significantly greater and earlier improvements compared with the other two groups in several criteria: PEF variability (17.9 +/- 2.5; 21.9 +/- 3.2; 23.7 +/- 3.3; P < 0.001); asthma symptom score (daytime) (1.6 +/- 0.5; 1 +/- 0.5; 2.0 +/- 0,5; P < 0.05); asthma symptom score (night-time) (1.2 +/- 0.4; 2.2 +/- 0.5; 16 +/- 0.6; P < 0001); and supplement alter butalin use (1.2 +/- 0.3; 1.8 +/- 0.5; 1.7 +/- 0.5; P < 0.05). However, at the end of the treatment, in all of the three groups studied, improvements were attained in overall asthma control and there was no statistical difference among the groups. Although there were no side effects which required the discontinuation of the treatment, it was observed that the maximum side effect was in the second group (20%, 31.6% and 20%, respectively). In conclusion, in patients who still have symptoms on treatment with inhaled corticosteroids, the addition of a long-acting beta2-agonist, leukotriene antagonists or sustained-release theophylline to the treatment is a logical approach, and, in addition to inhaled corticosteroids, any one of these second controller medications may be chosen in patients with moderate asthma.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Agonists / therapeutic use
  • Adult
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / therapeutic use
  • Budesonide / therapeutic use
  • Drug Therapy, Combination
  • Ethanolamines / therapeutic use
  • Female
  • Formoterol Fumarate
  • Glucocorticoids / therapeutic use*
  • Humans
  • Leukotriene Antagonists / therapeutic use
  • Male
  • Middle Aged
  • Phosphodiesterase Inhibitors / therapeutic use
  • Respiratory Mechanics / drug effects
  • Theophylline
  • Tosyl Compounds / therapeutic use


  • Adrenergic beta-Agonists
  • Anti-Asthmatic Agents
  • Bronchodilator Agents
  • Ethanolamines
  • Glucocorticoids
  • Leukotriene Antagonists
  • Phosphodiesterase Inhibitors
  • Tosyl Compounds
  • Budesonide
  • Theophylline
  • Formoterol Fumarate
  • zafirlukast