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

SummaryWe 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 FEV1 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 μg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 μg BD/salmeterol 100 μg BD/HFA-tiotropium bromide18 μg od; or (b) fluticasone propionate 500 μg BD/salmeterol 100 μg 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 salmeterol/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]. 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.