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      Repurposing Treatments to Enhance Innate Immunity. Can Statins Improve Neutrophil Functions and Clinical Outcomes in COPD?

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          Abstract

          Drug classes used in the treatment of Chronic Obstructive Pulmonary Disease (COPD) have not changed for many years, and none to date have shown disease-modifying activity. Statins are used to help reduce cardiovascular risk, which is high in many patients with COPD. Their use has been associated with improvements in some respiratory manifestations of disease and reduction in all-cause mortality, with greatest reductions seen in patients with the highest inflammatory burden. The mechanism for these effects is poorly understood. Neutrophils are key effector cells in COPD, and correlate with disease severity and inflammation. Recent in vitro studies have shown neutrophil functions are dysregulated in COPD and this is thought to contribute both to the destruction of lung parenchyma and to the poor responses seen in infective exacerbations. In this article, we will discuss the potential utility of statins in COPD, with a particular emphasis on their immune-modulatory effects as well as presenting new data regarding the effects of statins on neutrophil function in vitro.

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          Most cited references86

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          Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

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            Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.

            Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.
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              Characteristics of physical activities in daily life in chronic obstructive pulmonary disease.

              Quantification of physical activities in daily life in patients with chronic obstructive pulmonary disease has increasing clinical interest. However, detailed comparison with healthy subjects is not available. Furthermore, it is unknown whether time spent actively during daily life is related to lung function, muscle force, or maximal and functional exercise capacity. We assessed physical activities and movement intensity with the DynaPort activity monitor in 50 patients (age 64 +/- 7 years; FEV1 43 +/- 18% predicted) and 25 healthy elderly individuals (age 66 +/- 5 years). Patients showed lower walking time (44 +/- 26 vs. 81 +/- 26 minutes/day), standing time (191 +/- 99 vs. 295 +/- 109 minutes/day), and movement intensity during walking (1.8 +/- 0.3 vs. 2.4 +/- 0.5 m/second2; p < 0.0001 for all), as well as higher sitting time (374 +/- 139 vs. 306 +/- 108 minutes/day; p = 0.04) and lying time (87 +/- 97 vs. 29 +/- 33 minutes/day; p = 0.004). Walking time was highly correlated with the 6-minute walking test (r = 0.76, p < 0.0001) and more modestly to maximal exercise capacity, lung function, and muscle force (0.28 < r < 0.64, p < 0.05). Patients with chronic obstructive pulmonary disease are markedly inactive in daily life. Functional exercise capacity is the strongest correlate of physical activities in daily life.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                11 October 2016
                October 2016
                : 5
                : 10
                : 89
                Affiliations
                [1 ]Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK; g.m.walton@ 123456bham.ac.uk (G.M.W.); charandeepsadhra@ 123456hotmail.com (C.S.S.); TXP963@ 123456student.bham.ac.uk (T.P.)
                [2 ]Lung Function and Sleep, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TT, UK; james.stockley@ 123456uhb.nhs.uk
                [3 ]Respiratory Research, Research and Development, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TT, UK; diane.griffiths@ 123456uhb.nhs.uk
                Author notes
                [* ]Correspondence: E.Sapey@ 123456bham.ac.uk ; Tel.: +44-121-627-2000
                Article
                jcm-05-00089
                10.3390/jcm5100089
                5086591
                27727158
                82b9578c-f725-4063-8de8-62802ad6cc87
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 August 2016
                : 20 September 2016
                Categories
                Review

                neutrophil,inflammation,copd,statins,chemotaxis,simvastatin
                neutrophil, inflammation, copd, statins, chemotaxis, simvastatin

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