A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study
| Autor: | 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 |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Adolescent Vital Capacity Anti-Inflammatory Agents In Vitro Techniques Drug Administration Schedule Neutrophil Activation Young Adult Double-Blind Method Forced Expiratory Volume Atorvastatin Humans Pseudomonas Infections Aged Cross-Over Studies Sputum Middle Aged Anti-Bacterial Agents Bronchiectasis Treatment Outcome Cough Pseudomonas aeruginosa Quality of Life Cytokines Calcium Female Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | Chest. 152(2) |
| ISSN: | 1931-3543 |
| Popis: | There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa.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.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.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.ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov. |
| Databáze: | OpenAIRE |
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