Iron Replacement and Redox Balance in Non-Anemic and Mildly Anemic Iron Deficiency COPD Patients: Insights from a Clinical Trial

Abstract

In COPD patients, non-anemic iron deficiency (NAID) is a common systemic manifestation. We hypothesized that in COPD patients with NAID, iron therapy may improve systemic oxidative stress. The FACE (Ferinject assessment in patients with COPD and iron deficiency to improve exercise tolerance) study was a single-blind, unicentric, parallel-group, placebo-controlled clinical trial (trial registry: 2016-001238-89). Sixty-six patients were enrolled (randomization 2:1): iron arm, n = 44 and placebo arm, n = 22, with similar clinical characteristics. Serum levels of 3-nitrotyrosine, MDA-protein adducts, and reactive carbonyls, catalase, superoxide dismutase (SOD), glutathione, Trolox equivalent antioxidant capacity (TEAC), and iron metabolism biomarkers were quantified in both groups. In the iron-treated patients compared to placebo, MDA-protein adducts and 3-nitrotyrosine serum levels significantly declined, while those of GSH increased and iron metabolism parameters significantly improved. Hepcidin was associated with iron status parameters. This randomized clinical trial evidenced that iron replacement elicited a decline in serum oxidative stress markers along with an improvement in GSH levels in patients with stable severe COPD. Hepcidin may be a surrogate biomarker of iron status and metabolism in patients with chronic respiratory diseases. These findings have potential clinical implications in the management of patients with severe COPD.

Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance

“…All the participants were diagnosed according to the Global Strategy of Management of COPD patients (GOLD) criteria, in which the following parameters were included: spirometry values, number of exacerbations, and dyspnea score (modified medical research council, mMRC) [ 24 ]. Iron-deficient COPD patients (12 males) presented levels of hemoglobin > 12 g/dL in women and >13 g/dL in men, ferritin < 100 ng/mL, or ferritin 100–299 ng/mL with a transferrin saturation < 20% [ 21 , 23 , 25 , 26 ]. The study was approved on 17 January 2018 by the local Ethics Committee at Hospital del Mar (CEIm Parc de Salut Mar, registration # 2017/7691/I).…”

“…These findings were directly associated with both disease severity and the loss of mitochondrial content. Serum hepcidin was also shown to be a surrogate biomarker of iron status and metabolism in patients with chronic respiratory diseases including COPD [ 21 ]. Iron deficiency in COPD was also associated with reduced physical activity [ 22 ].…”

Chronic Obstructive Pulmonary Disease: The Present and Future

“…Monitoring markers of oxidative stress and miR genotyping for precision-based chemotherapy [10] Iron-deficient COPD IV iron replacement Monitoring hepcidin as a marker for non-anaemic iron deficiency [23] Antimicrobial-resistant COPD Targeted antibiotics based on culture sensitivities Use of colour charts to determine commencement of antibiotics [14] Key-LABA: long-acting β-agonists; LAMA: long-acting muscarinic antagonists; ICS: inhaled corticosteroids; HRQoL: health-related quality of life; CFTR: cystic fibrosis transmembrane receptor; miR: microRNA; VTE: venous thromboembolism; NIV: noninvasive ventilation; OSA/ORRF: obstructive sleep apnoea/obesity-related respiratory failure; COPD: chronic obstructive pulmonary disease; IV: intravenous.…”

“…As in the trial by Pérez-Peiró et al, these parameters can be measured biochemically by monitoring indirect markers of oxidative stress and antioxidants [ 23 ]. The authors demonstrated a decline in oxidative stress markers in non-anaemic COPD patients randomised to intravenous iron replacement within a short four-week study.…”

Pulmonary Arterial Pressure Changes Under Dobutamine Stress Echocardiography in Non-Anemic Iron Deficient COPD Subjects

“…Non-anemic iron deficiency (NAID) is a common metabolic disorder, affecting between 18% and 48% of subjects with chronic obstructive pulmonary disease (COPD). 1 , 2 Among the known pulmonary vascular effects of NAID are intracellular oxidative stress dysregulation, 3 pulmonary arterial smooth muscle proliferation, 4 and hyperreactive hypoxic pulmonary vasoconstriction (HPV). 5 Thus, NAID could be associated with increased systolic pulmonary arterial pressure (sPAP) under resting conditions in COPD subjects.…”