A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study
Pallavi Bedi, James D Chalmers, Catriona Graham, Andrea Clarke, Samantha Donaldson, Catherine Doherty, John R W Govan, Donald J Davidson, Adriano G Rossi, Adam T Hill, Pallavi Bedi, James D Chalmers, Catriona Graham, Andrea Clarke, Samantha Donaldson, Catherine Doherty, John R W Govan, Donald J Davidson, Adriano G Rossi, Adam T Hill
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.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed