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In the vastus lateralis and blood of severe COPD patients with\/without iron depletion, iron content and regulators, exercise capacity, and muscle function were evaluated in 40 severe COPD patients: non-iron deficiency (NID) and iron deficiency (ID) (20 patients\/group). In ID compared to NID patients, exercise capacity, muscle iron and ferritin content, serum transferrin saturation, hepcidin-25, and hemojuvelin decreased, while serum transferrin and soluble transferrin receptor and muscle IRP-1 and IRP-2 increased. Among all COPD, a significant positive correlation was detected between FEV1 and serum transferrin saturation. In ID patients, significant positive correlations were detected between serum ferritin, hepcidin, and muscle iron content and exercise tolerance and between muscle IRP-2 and serum ferritin and hepcidin levels. In ID severe COPD patients, iron content and its regulators are differentially expressed. A potential crosstalk between systemic and muscle compartments was observed in the ID patients. Lung function and exercise capacity were associated with several markers of iron metabolism regulation. Iron status should be included in the overall assessment of COPD patients given its implications in their exercise performance.<\/jats:p>","DOI":"10.3390\/nu14193929","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"3929","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria","family":"P\u00e9rez-Peir\u00f3","sequence":"first","affiliation":[{"name":"Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Pulmonology Department, Department of Medicine and Life Sciences (MELIS), Hospital del Mar, Medical Research Institute (IMIM), Parc de Salut Mar, Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6153-508X","authenticated-orcid":false,"given":"Mariela","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Pulmonology Department, Department of Medicine and Life Sciences (MELIS), Hospital del Mar, Medical Research Institute (IMIM), Parc de Salut Mar, Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain"},{"name":"Pulmonology Department, Hospital Universitario Sant Joan de Reus, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Mart\u00edn-Ontiyuelo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain"},{"name":"Department of Pulmonary Medicine, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Duran","sequence":"additional","affiliation":[{"name":"Scientific, Statistics, and Technical Department, Hospital del Mar-IMIM, Parc de Salut Mar, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-4011","authenticated-orcid":false,"given":"Diego A.","family":"Rodr\u00edguez-Chiarad\u00eda","sequence":"additional","affiliation":[{"name":"Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Pulmonology Department, Department of Medicine and Life Sciences (MELIS), Hospital del Mar, Medical Research Institute (IMIM), Parc de Salut Mar, Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Barreiro","sequence":"additional","affiliation":[{"name":"Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Pulmonology Department, Department of Medicine and Life Sciences (MELIS), Hospital del Mar, Medical Research Institute (IMIM), Parc de Salut Mar, Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/17476348.2021.1854737","article-title":"Extra-pulmonary manifestations of COPD and the role of pulmonary rehabilitation: A symptom-centered approach","volume":"15","author":"Machado","year":"2020","journal-title":"Expert Rev. 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