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      International Journal of COPD (submit here)

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      Indices of iron homeostasis correlate with airway obstruction in an NHANES III cohort

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          Abstract

          Cigarette smoking results in the accumulation of iron both systemically and locally, in the lung thereby causing imbalance in iron homeostasis. This disruption in iron homeostasis can be associated with oxidative stress and consequent tissue injury. Therefore, in this study, we tested the association between iron homeostasis and airway obstruction by examining a large cohort of smokers and non-smokers for relationships between 1) serum ferritin and iron concentrations and transferrin saturation and 2) forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), and their ratio (FEV 1/FVC). Data from the National Health and Examination Survey III were analyzed. The study population included persons aged 20 years and above with their following data recorded: race, gender, serum ferritin and iron concentrations, and transferrin saturation; the final sample number was 7,251. In the total population, Pearson correlation coefficients between 1) serum ferritin and iron concentrations and transferrin saturation and 2) FVC and FEV 1 were significantly positive; whereas those between 1) serum ferritin concentrations and transferrin saturation and 2) FEV 1/FVC were significantly negative. With separate analyses, serum ferritin concentrations demonstrated positive associations with FVC and FEV 1 but an inverse relationship with FEV 1/FVC in smokers and non-smokers. Serum ferritin levels increased with worsening airway obstruction among smokers, and its highest concentrations were found among those with the lowest values of FEV 1/FVC ratio (<60%). Comparable to cigarette smokers, serum ferritin concentrations among non-smokers were greatest in those with the lowest FEV 1/FVC ratio. Furthermore, elevated levels of serum iron and saturation of transferrin also corresponded with decreased FEV 1/FVC ratio among non-smokers. Thus, we conclude that indices of iron homeostasis are associated with airway obstruction in both smokers and non-smokers.

          Most cited references42

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          Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society.

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            American Thoracic Society Statement: Occupational contribution to the burden of airway disease.

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              Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

              Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.
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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
                2017
                18 July 2017
                : 12
                : 2075-2084
                Affiliations
                Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Chapel Hill, NC, USA
                Author notes
                Correspondence: Andrew J Ghio, Human Studies Facility, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, 104 Mason Farm Road, Chapel Hill, NC 27514, USA, Tel +1 919 966 0670, Fax +1 919 966 6271, Email ghio.andy@ 123456epa.gov
                Article
                copd-12-2075
                10.2147/COPD.S138457
                5529299
                28790810
                1289ab63-a0d0-4429-a6c1-5eba6aa417ee
                © 2017 Ghio and Hilborn. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. 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
                iron,ferritins,respiratory function tests,chronic obstructive pulmonary disease,spirometry,vital capacity,forced expiratory volume

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