title: Fluticasone/Salmeterol combination confers benefits in people with asthma who smoke.
abstract: BACKGROUND
  Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.
  
  
  METHODS
  Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 μg) two puffs bid (plus fluticasone placebo), or active fluticasone (250 μg) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV(1) (PC(20)).
  
  
  RESULTS
  In the patients who did not smoke, there were similar improvements in the methacholine PC(20) with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC(20) difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P < .01. The provocative dose of mannitol required to produce a 15% fall in FEV(1) (PD(15)) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEV(1) and airway resistance.
  
  
  CONCLUSIONS
  FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke.
  
  
  BACKGROUND
  ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov.
authors.affiliation: Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Ninewells Hospital and Medical School, University of Dundee, Scotland.
authors.forename: Karine L
authors.initials: KL
authors.lastname: Clearie
authors.affiliation: Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Ninewells Hospital and Medical School, University of Dundee, Scotland.
authors.forename: Lorna
authors.initials: L
authors.lastname: McKinlay
authors.affiliation: Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Ninewells Hospital and Medical School, University of Dundee, Scotland.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Williamson
authors.affiliation: Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Ninewells Hospital and Medical School, University of Dundee, Scotland. Electronic address: brianlipworth@gmail.com.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008353:Mannitol; D016210:Methacholine Chloride; D010919:Placebos; D012907:Smoking / Q000009:adverse effects*; D013147:Spirometry; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D010919:Placebos; D016210:Methacholine Chloride; D008353:Mannitol; D000420:Albuterol