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Anti-inflammatory effects of atorvastatin treatment in chronic obstructive pulmonary disease. A controlled pilot study

Authors

  • R.M. Mroz
  • P. Lisowski
  • A. Tycinska
  • J. Bierla
  • P.Z. Trzeciak
  • L. Minarowski
  • R. Milewski
  • A. Lisowska
  • P. Boros
  • B. Sobkowicz
  • A.M. Duszewska
  • E. Chyczewska
  • W.J. Musial
  • W. MacNee

Journal

  • Journal of Physiology and Pharmacology

Citation

  • J Physiol Pharmacol 66 (1): 111-128

Abstract

  • Observational studies have suggested that statins may have beneficial effects on outcomes in chronic obstructive pulmonary disease (COPD) patients. These effects may be mediated through an anti-inflammatory effect of statins. The purpose of this pilot-study was to determine whether statins have an anti-inflammatory effect on the lungs of COPD patients. We conducted randomized, controlled, parallel group pilot-study to compare the effects of atorvastatin (n=12) or placebo (n=6) on lung inflammation in patients with mild to moderate COPD. The primary endpoint was change in CD45+ cells expression measured by immunohistochemistry and changes in expression of genes measured using microarrays in lung biopsy (TBB) samples before and after 12 weeks of treatment with atorvastatin 40 mg/day. All subjects had spirometry, lung volumes, diffusing capacity of the lungsfor carbon monoxide (DLCO), St George's Respiratory Questionnaire (SGRQ), 6 minute walk distance (6MWD), serum lipids, hs-CRP, induced sputum (IS), bronchoscopy and TBB carried out at baseline and after treatment. TBB specimens were processed for histology, immunohistochemistry and genome-wide association studies (GWAS) profiling. Seventeen subjects completed the study. There was a significant improvement in SGRQ with mean SGRQ decreased by 12 points after treatment with atorvastatin (P=0.012). Atorvastatin treatment produced a significant 34% reduction in sputum neutrophil count, and a 57% reduction in CD45+ cells in lung biopsies (expressed as integrated optical density -IOD; median IOD 62.51% before, 27.01% after atorvastatin treatment, P=0.008). In patients' lung tissue atorvastatin treatment produced downregulation of key genes involved in inflammatory processes, immune response, and leukocyte activation. These data demonstrate the pulmonary anti-inflammatory effects of atorvastatin in COPD patients with the potential for beneficial clinical effects. Trial Registration: ClinicalTrials.gov: NCT01748279.


DOI

doi:journal/archive/02_15/articles/12_article.html