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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      Thiazolidinediones are associated with a reduced risk of COPD exacerbations

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          Abstract

          Background

          Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung.

          Objective

          The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation.

          Methods

          A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007. Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication. Multivariable negative binomial regression was performed with adjustment for potential confounding factors. The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations.

          Results

          We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications. COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group. In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81–0.92).

          Conclusion

          Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD.

          Most cited references27

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          The steroid and thyroid hormone receptor superfamily.

          Analyses of steroid receptors are important for understanding molecular details of transcriptional control, as well as providing insight as to how an individual transacting factor contributes to cell identity and function. These studies have led to the identification of a superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid. Although animals employ complex and often distinct ways to control their physiology and development, the discovery of receptor-related molecules in a wide range of species suggests that mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
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            PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines.

            The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor family of transcription factors, a large and diverse group of proteins that mediate ligand-dependent transcriptional activation and repression. Expression of PPAR-gamma is an early and pivotal event in the differentiation of adipocytes. Several agents that promote differentiation of fibroblast lines into adipocytes have been shown to be PPAR-gamma agonists, including several prostanoids, of which 15-deoxy-delta-prostaglandin J2 is the most potent, as well as members of a new class of oral antidiabetic agents, the thiazolidinediones, and a variety of non-steroidal anti-inflammatory drugs (NSAIDs). Here we show that PPAR-gamma agonists suppress monocyte elaboration of inflammatory cytokines at agonist concentrations similar to those found to be effective for the promotion of adipogenesis. Inhibition of cytokine production may help to explain the incremental therapeutic benefit of NSAIDs observed in the treatment of rheumatoid arthritis at plasma drug concentrations substantially higher than are required to inhibit prostaglandin G/H synthase (cyclooxygenase).
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              Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.

              Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that can be activated by various xenobiotics and natural fatty acids. These transcription factors primarily regulate genes involved in lipid metabolism and also play a role in adipocyte differentiation. We present the expression patterns of the PPAR subtypes in the adult rat, determined by in situ hybridization using specific probes for PPAR-alpha, -beta and -gamma, and by immunohistochemistry using a polyclonal antibody that recognizes the three rat PPAR subtypes. In numerous cell types from either ectodermal, mesodermal, or endodermal origin, PPARs are coexpressed, with relative levels varying between them from one cell type to the other. PPAR-alpha is highly expressed in hepatocytes, cardiomyocytes, enterocytes, and the proximal tubule cells of kidney. PPAR-beta is expressed ubiquitously and often at higher levels than PPAR-alpha and -gamma. PPAR-gamma is expressed predominantly in adipose tissue and the immune system. Our results suggest new potential directions to investigate the functions of the different PPAR subtypes.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2015
                10 August 2015
                : 10
                : 1591-1597
                Affiliations
                [1 ]Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, CT, USA
                [2 ]Division of Pulmonary and Critical Care, Yale University, New Haven, CT, USA
                [3 ]VA Puget Sound Health Care System, Department of Veterans Affairs, University of Washington, USA
                [4 ]Department of Health Services, University of Washington, USA
                [5 ]Division of Pulmonary and Critical Care, University of Washington, USA
                [6 ]Division of General Internal Medicine, University of Washington, USA
                [7 ]Gilead Sciences, Inc., Seattle, WA, USA
                Author notes
                Correspondence: Seppo T Rinne, Department of Veterans Affairs, VA Connecticut Healthcare System, 950 Campbell Avenue, Building 35a, Room 2-234, West Haven, CT 06516, USA, Tel +1 203 932 5711x3541, Email seppo.rinne@ 123456va.gov
                Article
                copd-10-1591
                10.2147/COPD.S82643
                4536761
                26300638
                b9a07a18-7a96-4258-8aea-4a6596f30948
                © 2015 Rinne et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Respiratory medicine
                peroxisome proliferator-activated receptors,glitazones,copd exacerbation,inflammation,cohort study

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