Abstract
In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients’ inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia.
Highlights
Introduction distributed under the terms andHypoxia, or lack of oxygen (O2 ), is characterized by decreased O2 arterial partial pressure (PaO2 ) and, decreased O2 supply to tissues
The main objective of this study is to characterize the oxidative state in patients affected by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia with the purpose to dissect the interplay among iron, inflammation and hypoxia, with two specific aims: (1) To evaluate a panel of redox balance biomarkers that may integrate the iron routine metabolism assays to monitor the patient’s inflammatory and oxidative state, to address their usefulness in validating interventions and to correct iron and redox imbalance
The minimal sample size was established through a priori Power Analysis for attaining significant (p < 0.05, two-tailed) differences based on the expected changes of the most significant parameters and the standard analytical reproducibility, assuming alpha = 0.05 and power = 0.80
Summary
Lack of oxygen (O2 ), is characterized by decreased O2 arterial partial pressure (PaO2 ) and, decreased O2 supply to tissues. By generating reactive O2 species (ROS), hypoxia upregulates several pro-inflammatory cytokines [1]. Physiological hypoxia is a strong inducer of hematopoiesis: when exposed to high altitude, healthy conditions of the Creative Commons. Antioxidants 2021, 10, 1460 subjects compensate hypoxia by augmenting red blood cell (RBC) production within a few days [2]. In this context, hypoxia adaptation implies increased need for iron to synthesize hemoglobin (Hb) to support hematopoiesis, which is met by augmenting iron entry in the circulation from duodenum, macrophages, and hepatocytes. By internalizing the iron transporter ferroportin, the protein hepcidin is known to down-regulate iron handling [3]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call