Neil C Thomson1, Catherine E Charron2, Rekha Chaudhuri3, Mark Spears4, Kazuhiro Ito5, Charles McSharry3. 1. Respiratory Medicine, Institute of Infection, Immunity and Inflammation, University of Glasgow, Gartnavel General Hospital, Glasgow, G12 OYN, Scotland, UK. Electronic address: neil.thomson@glasgow.ac.uk. 2. RespiVert Ltd, Imperial BioIncubator, Imperial College, London, UK. 3. Respiratory Medicine, Institute of Infection, Immunity and Inflammation, University of Glasgow, Gartnavel General Hospital, Glasgow, G12 OYN, Scotland, UK. 4. Respiratory Medicine, Forth Valley Royal Hospital, Larbert, UK. 5. Airway Disease Section, Imperial College, London, UK.
Abstract
BACKGROUND: Statins have pleiotropic immunomodulatory effects that may be beneficial in the treatment of asthma. We previously reported that treatment with atorvastatin improved asthma symptoms in smokers with asthma in the absence of a change in the concentration of a selection of sputum inflammatory mediators. OBJECTIVE: To determine the effects of atorvastatin alone and in combination with inhaled corticosteroid on a range of sputum cytokines, chemokines and growth factors implicated in the pathogenesis of asthma, and their association with asthma control questionnaire (ACQ) and/or asthma quality of life questionnaire (AQLQ) scores. METHODS: Sputum samples were analysed from a sub-group of 39 smokers with mild to moderate asthma recruited to a randomised controlled trial comparing atorvastatin (40 mg/day) versus placebo for four weeks, followed by inhaled beclometasone (400 μg/day) for a further four weeks. Induced sputum supernatant fluid was analysed (Luminex or biochemical analyses) for concentrations of 35 mediators. RESULTS:Sputum mediator concentrations were not reduced by inhaled beclometasone alone. Atorvastatin significantly reduced sputum concentrations of CCL7, IL-12p70, sCD40L, FGF-2, CCL4, TGF-α and MMP-8 compared with placebo and, when combined with inhaled beclometasone, reduced sputum concentrations of MMP-8, IL-1β, IL-10, MMP-9, sCD40L, FGF-2, IL-7, G-CSF and CCL7 compared to ICS alone. Improvements in ACQ and/or AQLQ scores with atorvastatin and ICS were associated with decreases in G-CSF, IL-7, CCL2 and CXCL8. CONCLUSION: Short-term treatment with atorvastatin alone or in combination with inhaled beclometasone reduces several sputum cytokines, chemokines and growth factors concentrations unresponsive to inhaled corticosteroids alone, in smokers with asthma.
RCT Entities:
BACKGROUND: Statins have pleiotropic immunomodulatory effects that may be beneficial in the treatment of asthma. We previously reported that treatment with atorvastatin improved asthma symptoms in smokers with asthma in the absence of a change in the concentration of a selection of sputum inflammatory mediators. OBJECTIVE: To determine the effects of atorvastatin alone and in combination with inhaled corticosteroid on a range of sputum cytokines, chemokines and growth factors implicated in the pathogenesis of asthma, and their association with asthma control questionnaire (ACQ) and/or asthma quality of life questionnaire (AQLQ) scores. METHODS: Sputum samples were analysed from a sub-group of 39 smokers with mild to moderate asthma recruited to a randomised controlled trial comparing atorvastatin (40 mg/day) versus placebo for four weeks, followed by inhaled beclometasone (400 μg/day) for a further four weeks. Induced sputum supernatant fluid was analysed (Luminex or biochemical analyses) for concentrations of 35 mediators. RESULTS: Sputum mediator concentrations were not reduced by inhaled beclometasone alone. Atorvastatin significantly reduced sputum concentrations of CCL7, IL-12p70, sCD40L, FGF-2, CCL4, TGF-α and MMP-8 compared with placebo and, when combined with inhaled beclometasone, reduced sputum concentrations of MMP-8, IL-1β, IL-10, MMP-9, sCD40L, FGF-2, IL-7, G-CSF and CCL7 compared to ICS alone. Improvements in ACQ and/or AQLQ scores with atorvastatin and ICS were associated with decreases in G-CSF, IL-7, CCL2 and CXCL8. CONCLUSION: Short-term treatment with atorvastatin alone or in combination with inhaled beclometasone reduces several sputum cytokines, chemokines and growth factors concentrations unresponsive to inhaled corticosteroids alone, in smokers with asthma.
Authors: Marcela T Taruselli; Elizabeth Motunrayo Kolawole; Amina Abdul Qayum; Tamara T Haque; Heather L Caslin; Daniel Abebayehu; Sydney A Kee; Jordan M Dailey; Kaitlyn G Jackson; Jason R Burchett; Andrew J Spence; Neha Pondicherry; Brian O Barnstein; Gregorio Gomez; David B Straus; John J Ryan Journal: Cell Immunol Date: 2021-11-24 Impact factor: 4.868
Authors: Heather L Caslin; Kasalina N Kiwanuka; Tamara T Haque; Marcela T Taruselli; H Patrick MacKnight; Anuya Paranjape; John J Ryan Journal: Front Immunol Date: 2018-04-26 Impact factor: 7.561