Combining tiotropium and salmeterol in COPD: Effects on airflow obstruction and symptoms

Respir Med. 2010 Jul;104(7):995-1004. doi: 10.1016/j.rmed.2010.02.017. Epub 2010 Mar 29.


Background: Clinical information on 24-h spirometric efficacy of combining tiotropium and salmeterol compared to single-agent therapy is lacking in patients with COPD.

Methods: A randomized, double-blind, four-way crossover study of 6-week treatment periods comparing combination therapy of tiotropium 18 microg plus qd or bid salmeterol 50 microg versus single-agent therapy. Serial 24-h spirometry (FEV(1), FVC), effects on dyspnea (TDI focal score) and rescue salbutamol use were evaluated in 95 patients.

Results: Tiotropium plus qd salmeterol was superior to tiotropium or salmeterol alone in average FEV(1) (0-24h) by 72 mL and 97 mL (p<0.0001), respectively. Compared to this qd regimen, combination therapy including bid salmeterol provided comparable daytime (0-12h: 12 mL, p=0.38) bronchodilator effects, but significantly more bronchodilation during the night-time (12-24h: 73 mL, p<0.0001). Clinically relevant improvements in TDI focal score were achieved with bronchodilator combinations including salmeterol qd or bid (2.56 and 2.71; p<0.005 versus components). Symptom benefit of combination therapies was also reflected in less need for reliever medication. All treatments were well tolerated.

Conclusion: Compared to single-agent therapy, combination therapy of tiotropium plus salmeterol in COPD provided clinically meaningful improvements in airflow obstruction and dyspnea as well as a reduction in reliever medication.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Airway Obstruction / drug therapy*
  • Airway Obstruction / physiopathology
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Bronchodilator Agents / administration & dosage*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Dyspnea / drug therapy*
  • Dyspnea / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Salmeterol Xinafoate
  • Scopolamine Derivatives / administration & dosage*
  • Spirometry
  • Tiotropium Bromide
  • Treatment Outcome


  • Bronchodilator Agents
  • Scopolamine Derivatives
  • Salmeterol Xinafoate
  • Albuterol
  • Tiotropium Bromide