title: Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma.
abstract: BACKGROUND
  Statins lower cholesterol and also exhibit anti-inflammatory properties. In vitro and animal studies have suggested they may be useful for the treatment of a number of inflammatory conditions.
  
  
  OBJECTIVE
  To evaluate the in vivo therapeutic potential of simvastatin as an anti-inflammatory agent in patients with asthma.
  
  
  METHODS
  Potential signal from treatment effect was optimized by withdrawing all anti-inflammatory treatment for the duration of the study. Participants received 1 month of daily simvastatin and 1 month of daily placebo in a randomized, double-blind crossover trial. A total of 16 patients completed per protocol. Asthmatic inflammation was evaluated by measuring exhaled tidal nitric oxide, alveolar nitric oxide, sputum and peripheral eosinophil count, methacholine hyperresponsiveness, salivary eosinophilic cationic protein, and C-reactive protein. Measurements of dynamic and static lung volumes and of cholesterol were also made.
  
  
  RESULTS
  After initial withdrawal of usual asthma medication, there was a 1.43 geometric mean fold increase (ie, 43% difference) in fraction of exhaled nitric oxide (95% CI, 1.15 to 1.78; P = .004). Compared with placebo, simvastatin led to a 0.86 geometric mean fold decrease (95% CI, 0.7 to 1.04; P = .15) in exhaled nitric oxide (ie, a 14% difference), and a -0.18 doubling dilution shift (95% CI, -1.90 to 1.55; P = 1.0) in methacholine hyperresponsiveness. There were no significant differences in other inflammatory outcomes, lung volumes, or airway resistance between simvastatin and placebo. Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol.
  
  
  CONCLUSIONS
  There is no evidence to suggest simvastatin has anti-inflammatory activity in patients with asthma.
  
  
  CONCLUSIONS
  Simvastatin is not useful for the treatment of asthma.
authors.affiliation: Asthma and Allergy Research Group, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Menzies
authors.forename: Arun
authors.initials: A
authors.lastname: Nair
authors.forename: Karen T
authors.initials: KT
authors.lastname: Meldrum
authors.forename: Dawn
authors.initials: D
authors.lastname: Fleming
authors.forename: Martyn
authors.initials: M
authors.lastname: Barnes
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; D019821:Simvastatin