Duca Lorena, Ottolenghi Sara, Coppola Silvia, Rinaldo Rocco, Dei Cas Michele, Rubino Federico Maria, Paroni Rita, Samaja Michele, Chiumello Davide Alberto, Motta Irene
General Medicine Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy.
Antioxidants (Basel). 2021 Sep 14;10(9):1460. doi: 10.3390/antiox10091460.
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.
在患有急性呼吸窘迫综合征（ARDS）、慢性阻塞性肺疾病（COPD）和2019冠状病毒病（COVID-19）的患者中，尚不清楚的机制会对缺氧的造血反应产生负面影响。尽管受到生理性缺氧刺激，但肺部缺氧患者通常会出现贫血，这最终可能使病情复杂化。为了描述这种非适应性反应，我们剖析了急性（ARDS和COVID-19）或慢性（COPD）缺氧患者体内氧化还原状态、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，这些标志物可与常规铁代谢检测相结合，以监测患者的炎症和氧化状态。我们测量了20例ARDS患者、20例非卧床COPD患者、9例COVID-19 ARDS样患者以及10例年龄匹配的非缺氧健康志愿者（对照组）的氧化还原和造血调节因子。所有检查的病理状况均导致缺氧，ARDS和COVID-19抑制造血反应，但对促红细胞生成素无显著影响。所有患者的游离铁均高于对照组，ARDS和COVID-19患者的铁调素和可溶性转铁蛋白受体水平更高。氧化还原状态和抗氧化屏障的所有标志物在ARDS和COVID-19中均过度表达。然而，尽管所有患者体内谷胱甘肽水平均降低，但作为氧化还原失衡候选标志物的谷胱甘肽化血红蛋白在ARDS中尤其低。尽管所有组的铁调节均功能失调，但ARDS中抗氧化屏障的降低以及COVID-19中程度较轻的降低可能会引发更大的炎症反应，进而导致贫血。
