The “Iron”-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

Cloonan, Suzanne M.; Mumby, Sharon; Adcock, Ian M.; Choi, Augustine M.K.; Chung, Kian Fan; Quinlan, Gregory J.

doi:10.1164/rccm.201702-0311pp

Cited by 81 publications

(85 citation statements)

References 123 publications

(176 reference statements)

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“…Whether this applies to other chronic conditions where inflammation and ID often coexist remains to be determined, and active clinical research is needed [131]. A further novel example in this sense could be represented by chronic obstructive pulmonary disease (COPD), where a previously unrecognized detrimental role of ID would merit adequate addressing in the future [132].…”

Section: Expanding Spectrum Of Clinical Use Of IV Ironmentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

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Section: Expanding Spectrum Of Clinical Use Of IV Ironmentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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“…Likewise, neutrophils release iron regulatory molecules helping sequester free iron [9][10][11]. Human lung iron levels range between 0.4-0.9 mg/g, and~10 μg iron are exposed to lungs daily at a normal rate of breathing from the atmosphere [12]. Exposure to higher iron levels through inhalation of iron-containing particulate matter provides catalytically active iron resulting in tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

et al. 2019

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Nutrient iron sequestration is the most significant form of nutritional immunity and causes bacterial pathogens to evolve strategies of host iron scavenging. Cigarette smoking contains iron particulates altering lung and systemic iron homeostasis, which may enhance colonization in the lungs of patients suffering chronic obstructive pulmonary disease (COPD) by opportunistic pathogens such as nontypeable. NTHi is a heme auxotroph, and the NTHi genome contains multiple heme acquisition systems whose role in pulmonary infection requires a global understanding. In this study, we determined the relative contribution to NTHi airway infection of the four heme-acquisition systems HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF that are located at the bacterial outer membrane or the periplasm. Our computational studies provided plausible 3D models for HbpA, SapA, PE, and HxuA interactions with heme. Generation and characterization of single mutants in the hxuCBA, hpe, sapA, and hbpA genes provided evidence for participation in heme binding-storage and inter-bacterial donation. The hxuA, sapA, hbpA, and hpe genes showed differential expression and responded to heme. Moreover, HxuCBA, PE, SapABCDFZ, and HbpA-DppBCDF presented moonlighting properties related to resistance to antimicrobial peptides or glutathione import, together likely contributing to the NTHi-host airway interplay, as observed upon cultured airway epithelia and in vivo lung infection. The observed multifunctionality was shown to be system-specific, thus limiting redundancy. Together, we provide evidence for heme uptake systems as bacterial factors that act in a coordinated and multi-functional manner to subvert nutritional-and other sources of host innate immunity during NTHi airway infection.

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“…FRTs are among the major iron-containing proteins, and its serum level is directly proportional to total body iron stores. This protein functions as one of the endogenous antioxidants that prevents the harmful effects of iron-catalysed oxidative stress by reducing the influx of iron into the plasma 22 . In the iron overload condition, like β-TM, hemochromatosis or inflammation, the majority of the excess iron sequesters in FRT 23 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

Smesam¹,

Qazmooz²,

Arjmand³

et al. 2019

Preprint

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Beta thalassemia major (β-TM) disorder characterized by the lack, or severe reduction in the production of hemoglobin β-globin chains. The standard protocol for the management of β-TM is blood transfusion and iron chelation therapy to reduce the iron overload state. The present study aimed to investigate the relationships between two iron regulatory hormones, hepcidin (HEPC) and erythroferrone (ERFE) levels and iron status parameters (ISPs) in Iraqi patients with β-TM. ISPs and hormones were measured in sixty patients and compared with thirty healthy controls. The results indicated significant changes in different iron status parameters, while ferritin (FRT) with the ~11 fold increase showed the most change. Significant reduction in HEPC and increase in ERFE levels were detected in patients as compared to the control group, while no direct correlation was identified with the other measured ISPs. Receiver operating characteristic (ROC) analysis showed that the z-score of the composite of ERFE+FRT has a full diagnostic ability for β-TM. In conclusion, our finding indicated the correlation between different ISPs, FRT as the leading predictor of iron overload and tow main iron regulatory hormones.

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The “Iron”-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

Cited by 81 publications

References 123 publications

Modern iron replacement therapy: clinical and pathophysiological insights

Modern iron replacement therapy: clinical and pathophysiological insights

Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

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The “Iron”-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

Cited by 81 publications

References 123 publications

Modern iron replacement therapy: clinical and pathophysiological insights

Modern iron replacement therapy: clinical and pathophysiological insights

Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent &beta;-Thalassemia Major Patients

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Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients