Rationale Smoking is known to increase airway inflammation and induce relative resistance to of inhaled steroids.
Objectives This study aimed to evaluate the effects of adding salmeterol to fluticasone (FPSM) versus doubling the dose of fluticasone (FP) in smoking and non-smoking asthmatics.
Methods 16 non-smoking and 15 smoking asthmatics were randomised to completion in a double blind, placebo-controlled crossover study. They received either FP/SM pMDI (125/25 mg) two puffs bid (+FP placebo) or active FP 250 mg pMDI two puffs bid (+FPSM placebo), for 2 weeks each, with baselines after 1–2 week run-in and wash-out periods. The primary outcome was change from baseline in methacholine PC20.
Results In non-smokers there were similar improvements with FP and FPSM. Smokers demonstrated no change in methacholine PC20 following treatment with FP, however FPSM conferred significant benefit: 1.6 doubling dilution (95% CI 1.0 to 2.2), p<0.01. Smokers gained proportionally greater benefit from FPSM minus FP compared to smokers: 1.4dd (95% CI 0.01 to 2.8), p=0.047. Similar changes were observed in FEV1 and IOS, and a similar but non-significant trend was seen with AHR to mannitol.
Conclusion Combination FPSM confers greater improvements in AHR and airway caliber in smoking asthmatics, as compared to double the dose of FP alone. It is likely that in the face of the relative steroid resistance, the smooth muscle stabilisation conferred by SM becomes of greater clinical importance.