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

Abstract

We hypothesized that iron content and regulatory factors, which may be involved in exercise tolerance, are differentially expressed in systemic and muscle compartments in iron deficient severe chronic obstructive pulmonary disease (COPD) patients. 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.

Nitrosative and Oxidative Stress, Reduced Antioxidant Capacity, and Fiber Type Switch in Iron-Deficient COPD Patients: Analysis of Muscle and Systemic Compartments

“…Consistently, levels of protein tyrosine nitration as measured by the 3-nitrotyrosine marker were significantly greater in the lower limb muscles and systemic compartments of COPD patients with iron deficiency as compared to patients with normal iron content. These are relevant findings that point towards the existence of a crosstalk between the two compartments as also previously reported in a study [ 15 ] in which a similar approach was used. The confirmation of the crosstalk between these two specific compartments has clinical implications, since therapeutic strategies will be able to target the two compartments simultaneously.…”

“…As previously described, specimens from the vastus lateralis were obtained using the open biopsy technique from all the study patients [ 15 , 19 , 20 , 21 , 23 ]. Muscle samples were immediately frozen in liquid nitrogen and then stored at −80 °C (temperature under alarm control) for the molecular biology experiments.…”

“…In patients with COPD, iron depletion has also been documented in previous investigations [ 10 , 11 , 12 , 13 , 14 ]. In a recent study [ 15 ], a potential crosstalk between systemic and muscle compartments was observed in COPD patients with iron deficiency. Moreover, lung function and exercise capacity were associated with several markers involved in the regulation of iron metabolism in the same cohort of patients [ 15 ].…”

“…In a recent study [ 15 ], a potential crosstalk between systemic and muscle compartments was observed in COPD patients with iron deficiency. Moreover, lung function and exercise capacity were associated with several markers involved in the regulation of iron metabolism in the same cohort of patients [ 15 ]. Hence, in iron content depletion is common among patients with chronic diseases, including COPD [ 10 , 11 , 12 , 16 , 17 ].…”

Prevalence of sarcopenia in patients with COPD through different musculature measurements: An updated meta-analysis and meta-regression

“…Characterized by abnormal extra-pulmonary manifestations and chronic inflammation, chronic obstructive pulmonary disease (COPD), negatively affects the quality of life of patients and physical function (decreased physical activity endurance levels, strength, and mass of muscles) ( 1 , 2 ). These aforementioned factors are also strongly associated with the onset and progression of sarcopenia.…”