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

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.

• Authors: 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
• Journal: Chest (Chest) Vol. 152 Issue 2 Pg. 368-378 (08 2017) ISSN: 1931-3543 [Electronic] United States
• PMID: 28554732 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Adolescent
• Adult
• Aged
• Anti-Bacterial Agents (therapeutic use)
• Anti-Inflammatory Agents (administration & dosage)
• Atorvastatin (administration & dosage)
• Bronchiectasis (complications, 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, drug therapy)
• Pseudomonas aeruginosa (isolation & purification)
• Quality of Life
• Sputum (microbiology)
• Treatment Outcome
• Vital Capacity (drug effects)
• Young Adult