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

Pallavi Bedi; 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

doi:10.1016/j.chest.2017.05.017

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 language	English
Pages (from-to)	368-378
Number of pages	11
Journal	Chest
Volume	152
Issue number	2
Early online date	26 May 2017
DOIs	https://doi.org/10.1016/j.chest.2017.05.017
Publication status	Published - Aug 2017

Keywords

infection
inflammation
microbiology

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Author Accepted Manuscript
© 2017 Published by Elsevier Inc under license from the American College of Chest Physicians. Under a Creative Commons license Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Accepted author manuscript, 712 KBLicence: CC BY-NC-ND
Final Published Version
Copyright 2017 The Authors. Published by Elsevier Inc under license from the American College of Chest Physicians. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Final published version, 578 KBLicence: CC BY-NC-ND

Cite this

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

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.",

keywords = "infection, inflammation, microbiology",

author = "Pallavi Bedi and Chalmers, {James D.} and Catriona Graham and Andrea Clarke and Samantha Donaldson and Doherty, {Catherine J.} and Govan, {John R. W.} and Davidson, {Donald J.} and Rossi, {Adriano G.} and Hill, {Adam T.}",

note = "Copyright {\textcopyright} 2017. Published by Elsevier Inc.",

year = "2017",

month = aug,

doi = "10.1016/j.chest.2017.05.017",

language = "English",

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T1 - A randomised control trial of atorvastatin in bronchiectasis patients infected with Pseudomonas aeruginosa- a proof of concept study

AU - Bedi, Pallavi

AU - Chalmers, James D.

AU - Graham, Catriona

AU - Clarke, Andrea

AU - Donaldson, Samantha

AU - Doherty, Catherine J.

AU - Govan, John R. W.

AU - Davidson, Donald J.

AU - Rossi, Adriano G.

AU - Hill, Adam T.

PY - 2017/8

Y1 - 2017/8

N2 - 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.

AB - 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.

KW - infection

KW - inflammation

KW - microbiology

U2 - 10.1016/j.chest.2017.05.017

DO - 10.1016/j.chest.2017.05.017

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SN - 0012-3692

VL - 152

SP - 368

EP - 378

JO - Chest

JF - Chest

IS - 2

ER -

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

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