title: Anti-inflammatory effects of atorvastatin treatment in chronic obstructive pulmonary disease. A controlled pilot study.
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 lungs for carbon monoxide (DLCO), St George's Respiratory Questionnaire (SGRQ), 6 minute walk distance (6 MWD), 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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01748279.
authors.affiliation: Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland. robmroz@wp.pl.
authors.forename: R M
authors.initials: RM
authors.lastname: Mroz
authors.forename: P
authors.initials: P
authors.lastname: Lisowski
authors.forename: A
authors.initials: A
authors.lastname: Tycinska
authors.forename: J
authors.initials: J
authors.lastname: Bierla
authors.forename: P Z
authors.initials: PZ
authors.lastname: Trzeciak
authors.forename: L
authors.initials: L
authors.lastname: Minarowski
authors.forename: R
authors.initials: R
authors.lastname: Milewski
authors.forename: A
authors.initials: A
authors.lastname: Lisowska
authors.forename: P
authors.initials: P
authors.lastname: Boros
authors.forename: B
authors.initials: B
authors.lastname: Sobkowicz
authors.forename: A M
authors.initials: AM
authors.lastname: Duszewska
authors.forename: E
authors.initials: E
authors.lastname: Chyczewska
authors.forename: W J
authors.initials: WJ
authors.lastname: Musial
authors.forename: W
authors.initials: W
authors.lastname: MacNee
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011044:Poland; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D020127:Recovery of Function; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D005819:Genetic Markers; D018836:Inflammation Mediators; D000069059:Atorvastatin