A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study

Chest. 2017 Aug;152(2):368-378. doi: 10.1016/j.chest.2017.05.017. Epub 2017 May 26.

Abstract

Background: There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa.

Methods: Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months.

Results: Twenty-seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, -0.57-4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (-5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C-reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 μM reduced formyl-methionyl-leucyl phenylalanine-induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation.

Conclusions: We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation.

Trial registry: ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov.

Keywords: infection; inflammation; microbiology.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Inflammatory Agents / administration & dosage*
  • Atorvastatin / administration & dosage*
  • Bronchiectasis / complications
  • Bronchiectasis / drug therapy*
  • Calcium / metabolism
  • Cough / etiology
  • Cross-Over Studies
  • Cytokines
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Neutrophil Activation / drug effects
  • Pseudomonas Infections / complications*
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / isolation & purification
  • Quality of Life
  • Sputum / microbiology
  • Treatment Outcome
  • Vital Capacity / drug effects
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Cytokines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Calcium

Associated data

  • ClinicalTrials.gov/NCT01299194