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

作者：Bedi Pallavi^*; Chalmers James D; Graham Catriona; Clarke Andrea; Donaldson Samantha; Doherty Catherine; Govan John R W; Davidson Donald J; Rossi Adriano G; Hill Adam T

来源：Chest, 2017, 152(2): 368-378.

DOI：10.1016/j.chest.2017.05.017

• infection
• inflammation
• microbiology

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 mM 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.

• 出版日期2017-8