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.

中文翻译：

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慢性阻塞性肺病、急性呼吸窘迫综合征和冠状病毒病 2019 的差异氧化还原状态和铁调节

在受急性呼吸窘迫综合征 (ARDS)、慢性阻塞性肺病 (COPD) 和 2019 年冠状病毒病 (COVID-19) 影响的患者中，不清楚的机制会对造血对缺氧的反应产生负面影响。尽管受到生理性缺氧的刺激，肺缺氧患者通常会出现贫血，这可能最终使结果复杂化。为了表征这种非适应性反应，我们剖析了受到急性（ARDS 和 COVID-19）或慢性（COPD）缺氧挑战的患者的氧化还原状态、铁调节和炎症之间的相互作用。为此，我们评估了一组氧化还原状态生物标志物，这些生物标志物可以整合常规铁代谢检测以监测患者的炎症和氧化状态。我们测量了 20 名 ARDS 患者的氧化还原和造血调节因子，20 名非卧床 COPD 患者、9 名 COVID-19 ARDS 样患者和 10 名年龄匹配的非缺氧健康志愿者（对照）。所有检查的病理条件都会引起缺氧，ARDS和COVID-19抑制造血反应，而对促红细胞生成素没有显着影响。所有患者的游离铁均高于对照组，ARDS 和 COVID-19 中铁调素和可溶性转铁蛋白受体水平较高。氧化还原状态和抗氧化屏障的所有标志物在 ARDS 和 COVID-19 中过度表达。然而，尽管所有患者都存在谷胱甘肽水平降低，但谷胱甘肽血红蛋白（氧化还原失衡的候选标志物）在 ARDS 中的含量特别低。尽管所有组的铁调节功能失调，ARDS 中的抗氧化屏障降低，COVID-19 中的程度较低，