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

We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or satmeterol and tiotropium. Eighteen life-tong non-smoking severe asthmatics [mean FEV, 1.491 (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 mu g daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 mu g BD/salmeterol 100 mu g BD/HFA-tiotropium bromi 18 mu g od; or (b) fluticasone propionate 500 mu g BD/salmeterol 100 mu g 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 H2O/l/s [p < 0.05]. Adding saimeterot/tiotropium produced similar improvements in PEF and RAW, but also improved FEV1 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]. RVand 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. (c) 2006 Elsevier Ltd. All rights reserved.