Pavlisa Gordana, Vrbanic Veljko, Kusec Vesna, Jaksic Branimir
Special Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, Croatia.
Clin Sci (Lond). 2004 Jan;106(1):43-51. doi: 10.1042/CS20030165.
In order to determine the initial values and dynamic changes of EPO (erythropoietin) after therapy, 57 consecutively presenting, typical COPD (chronic obstructive pulmonary disease) patients with chronic hypoxia and acute exacerbated serum EPO levels were serially measured. Initial mean EPO levels were slightly above the normal range (41.4 +/- 83.5 units/l), but in the majority of patients the initial EPO levels were significantly reduced. Following the correction of hypoxaemia, mean EPO levels decreased to 14.1 +/- 16.9 units/l (P=0.0093). However, not all COPD patients showed this pattern; in an important subset of patients (36.8%), who had initially lower EPO levels and lower erythrocyte count, EPO levels were significantly increased (by more than 60%; P=0.0028) on the second day of treatment, despite correction of the hypoxaemia. This finding was unexpected and paradoxical when compared with physiological studies addressing the same issue. The data presented support previous reports of variable EPO levels in severely hypoxic COPD patients and suggest that the haematological response is already hampered at an early stage, at the level of EPO production, and much less likely at later steps in the haemopoietic response by failure to respond to elevated EPO levels. Our data are consistent with recent discoveries that the O2 sensing and regulation of EPO production is a complex process in which multiple factors, including cytokines and therapeutic agents, play a role by enhancing or inhibiting the response. We believe that further studies on this clinical condition are complementary to basic physiological research and may help to elucidate the role of cytokines and other individual factors in complex clinical hypoxic situations.
为了确定治疗后促红细胞生成素(EPO)的初始值和动态变化,对57例连续就诊的典型慢性阻塞性肺疾病(COPD)患者进行了慢性低氧血症和急性加重期血清EPO水平的系列测定。EPO初始平均水平略高于正常范围(41.4±83.5单位/升),但大多数患者的EPO初始水平显著降低。低氧血症纠正后,EPO平均水平降至14.1±16.9单位/升(P = 0.0093)。然而,并非所有COPD患者都呈现这种模式;在一个重要的患者亚组(36.8%)中,他们最初的EPO水平和红细胞计数较低,尽管低氧血症得到了纠正,但在治疗的第二天EPO水平仍显著升高(超过60%;P = 0.0028)。与针对同一问题的生理学研究相比,这一发现出乎意料且自相矛盾。所呈现的数据支持先前关于严重低氧COPD患者EPO水平变化的报道,并表明血液学反应在早期EPO产生水平就已受到阻碍,而在造血反应的后期阶段因未能对升高的EPO水平作出反应而受到阻碍的可能性要小得多。我们的数据与最近的发现一致,即EPO产生的氧感应和调节是一个复杂的过程,其中包括细胞因子和治疗药物在内的多种因素通过增强或抑制反应发挥作用。我们认为,对这种临床情况的进一步研究对基础生理学研究具有补充作用,可能有助于阐明细胞因子和其他个体因素在复杂临床低氧情况下的作用。