title: [Bronchodilator efficacy of combined salmeterol and tiotropium in patients with chronic obstructive pulmonary disease].
abstract: OBJECTIVE
  Bronchodilators are still the most effective drugs for controlling the symptoms of chronic obstructive pulmonary disease (COPD). Tiotropium bromide, a long-acting anticholinergic drug, has recently been added to the therapeutic arsenal for the disease. To date, there have been no studies combining 2 long-acting bronchodilators. The aim of the present trial was to determine whether the combination of salmeterol and tiotropium improved lung function in COPD patients more than either of them alone.
  
  
  METHODS
  Twenty-two patients (20 men) diagnosed with COPD, with a mean age of 64 years, were enrolled in this cross-over trial. Active smokers were excluded. Mean (SD) forced expiratory volume in 1 second (FEV1) was 43% (14%) of predicted. All patients were experienced in the use of inhalers. The following 3 therapeutic combinations were randomly assigned to be administered for a 1-week period: a) fluticasone (500 microg/12 h), salmeterol (50 microg/12 h) and placebo; b) fluticasone, tiotropium (18 microg/24 h), and placebo; and c) fluticasone, salmeterol, and tiotropium. At the end of each period, forced spirometry was performed before inhalation of the therapeutic combination (between 8:30 am and 9:30 am) and 2 hours after inhalation. Throughout the week, morning peak flow rates measured immediately before inhalation were recorded, and there was a 48-hour wash-out period between each therapeutic combination.
  
  
  RESULTS
  All the patients completed the protocol. There were no significant differences in preinhalation or postinhalation FEV1 with salmeterol compared to tiotropium (preinhalation FEV1, 1.17 [0.55] L compared to 1.19 [0.49] L; postinhalation FEV1, 1.32 [0.65] L compared to 1.29 [0.61] L). In all cases postinhalation FEV1 was significantly higher than preinhalation FEV1. The combination of fluticasone, salmeterol, and tiotropium proved superior to the other 2 combinations with respect to both preinhalation FEV1 and postinhalation FEV1 (preinhalation FEV1, 1.32 [0.56] L, [P<.03 in both comparisons]; postinhalation FEV1, 1.49 [0.68] L [P<.001 in both comparisons]). Peak flow rate was also significantly higher with the combination of the 2 bronchodilators (345 L/min compared to 291 L/min and 311 mL, respectively [P <.04 in both cases]). There were no notable side effects.
  
  
  CONCLUSIONS
  In terms of improvement in lung function, the combination of salmeterol and tiotropium together with fluticasone is more effective in patients with moderate-to-severe COPD than either of the 2 bronchodilators administered alone.
authors.affiliation: Sección de Neumología, Complexo Hospitalario de Pontevedra, Mourente, Pontevedra, España. adolfobalo@eresmas.com
authors.forename: A
authors.initials: A
authors.lastname: Baloira Villar
authors.forename: C
authors.initials: C
authors.lastname: Vilariño Pombo
mesh_terms: D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D013147:Spirometry; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D010919:Placebos; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000069447:Tiotropium Bromide