A randomised control trial of atorvastatin in bronchiectasis patients infected with Pseudomonas aeruginosa- a proof of concept study

Pallavi Bedi (Lead / Corresponding author), James D. Chalmers, Catriona Graham, Andrea Clarke, Samantha Donaldson, Catherine J. Doherty, John R. W. Govan, Donald J. Davidson, Adriano G. Rossi, Adam T. Hill

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Abstract

Introduction: There are no randomised control trials of statin therapy in patients with severe bronchiectasis, chronically infected with Pseudomonas aeruginosa.

Methods: 32 patients chronically infected with P. aeruginosa were recruited in this double blind cross over RCT. 16 patients were recruited in each arm, given atorvastatin 80mg or placebo for 3months, followed by a washout period for 6weeks, crossed over and administered the alternative therapy for 3months.

Results: 27 patients completed the study. Atorvastatin did not significantly improve the primary endpoint of cough as measured by Leicester Cough Questionnaire [mean difference=1.92, 95% CI for difference (-0.57, 4.41), p=0.12]. However, atorvastatin treatment resulted in improved St Georges Respiratory Questionnaire (-5.62points, p=0.016), reduced serum CXCL8 (p=0.04), TNF (p=0.01) and ICAM1 (p=0.04). There was a trend towards improvement in serum CRP and serum neutrophil counts (p=0.07 and p=0.06 respectively). In vitro, we demonstrated that atorvastatin 10μM reduced fMLF induced upregulation of CD11b expression and changes in calcium flux reflecting an ability to decrease neutrophil activation.

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

Original languageEnglish
Pages (from-to)368-378
Number of pages11
JournalChest
Volume152
Issue number2
Early online date26 May 2017
DOIs
Publication statusPublished - Aug 2017

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Keywords

  • infection
  • inflammation
  • microbiology

Cite this

Bedi, P., Chalmers, J. D., Graham, C., Clarke, A., Donaldson, S., Doherty, C. J., Govan, J. R. W., Davidson, D. J., Rossi, A. G., & Hill, A. T. (2017). A randomised control trial of atorvastatin in bronchiectasis patients infected with Pseudomonas aeruginosa- a proof of concept study. Chest, 152(2), 368-378. https://doi.org/10.1016/j.chest.2017.05.017