A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma

Respir Med. 2007 Jun;101(6):1218-28. doi: 10.1016/j.rmed.2006.11.001. Epub 2006 Dec 18.


We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0-69.0)l/min [p<0.05]; and RAW of 0.98 (0.14-1.8)cm H(2)O/l/s [p<0.05]. Adding salmeterol/tiotropium produced similar improvements in PEF and RAW, but also improved FEV(1) by 0.17 (0.01-0.32)l [p<0.05]; FVC 0.24 (0.05-0.43)l [p<0.05] and reduced exhaled NO by 2.86 (0.12-5.6)ppb [p<0.05]. RV and TLC were not altered by either treatment; there were no significant changes in symptoms or quality of life compared with baseline. Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuterol / analogs & derivatives
  • Albuterol / therapeutic use
  • Androstadienes / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Breath Tests / methods
  • Bronchodilator Agents / therapeutic use*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluticasone
  • Forced Expiratory Volume / drug effects
  • Glucocorticoids / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Plethysmography, Whole Body
  • Quality of Life
  • Salmeterol Xinafoate
  • Scopolamine Derivatives / therapeutic use
  • Tiotropium Bromide
  • Treatment Outcome
  • Vital Capacity / drug effects


  • Androstadienes
  • Bronchodilator Agents
  • Glucocorticoids
  • Scopolamine Derivatives
  • Nitric Oxide
  • Salmeterol Xinafoate
  • Fluticasone
  • Albuterol
  • Tiotropium Bromide