• Iron In Lung Disease

    From ironjustice@21:1/5 to All on Wed Apr 11 10:37:47 2018
    Indices of iron homeostasis correlate with airway obstruction in an NHANES III cohort.
    Ghio AJ1, Hilborn ED1.
    Int J Chron Obstruct Pulmon Dis. 2017 Jul 18;12:2075-2084.
    doi: 10.2147/COPD.S138457. eCollection 2017.
    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 (FEV1), and their ratio (FEV1/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 FEV1 were significantly positive; whereas those between 1) serum ferritin concentrations and transferrin saturation and 2) FEV1/FVC were significantly negative. With separate analyses, serum ferritin concentrations
    demonstrated positive associations with FVC and FEV1 but an inverse relationship with FEV1/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 FEV1/FVC ratio (<60%). Comparable to cigarette smokers, serum ferritin concentrations among non-smokers were greatest in those with the lowest FEV1/FVC ratio. Furthermore, elevated levels of serum iron and saturation of
    transferrin also corresponded with decreased FEV1/FVC ratio among non-smokers. Thus, we conclude that indices of iron homeostasis are associated with airway obstruction in both smokers and non-smokers.

    chronic obstructive pulmonary disease; ferritins; forced expiratory volume; iron; respiratory function tests; spirometry; vital capacity

    PMID: 28790810 PMCID: PMC5529299 DOI: 10.2147/COPD.S138457


    Association of serum ferritin levels with smoking and lung function in the Korean adult population: analysis of the fourth and fifth Korean National Health and Nutrition Examination Survey.
    Lee CH1, Goag EK1, Lee SH1, Chung KS1, Jung JY1, Park MS1, Kim YS1, Kim SK1, Chang J1, Song JH1.
    Int J Chron Obstruct Pulmon Dis. 2016 Nov 29;11:3001-3006. eCollection 2016.

    Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron
    homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and
    serum ferritin concentration in a large cohort representative of the Korean adult population.

    Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study.

    The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin
    were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable
    regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex,
    height, and weight.

    Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive
    severity. While smoking amount was inversely related to lung function, higher levels of serum ferritin were associated with enhanced spirometric results in a representative sample of the general Korean adult population. Future prospective studies will be
    needed to clarify the causality between serum ferritin and lung functions and their role in COPD morbidity.

    airway obstruction; ferritin; smoking

    PMID: 27942209 PMCID: PMC5136357 DOI: 10.2147/COPD.S116982


    Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.
    Philippot Q1, Deslée G2, Adair-Kirk TL3, Woods JC4, Byers D3, Conradi S4, Dury S5, Perotin JM2, Lebargy F5, Cassan C6, Le Naour R6, Holtzman MJ3, Pierce RA3.
    PLoS One. 2014 May 1;9(5):e96285. doi: 10.1371/journal.pone.0096285. eCollection 2014.

    Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and
    Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these
    correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD
    1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay. Percentage of iron-
    positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)). The
    alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression
    of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively). In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin
    correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress.

    PMID: 24789352 PMCID: PMC4006868 DOI: 10.1371/journal.pone.0096285

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