Calfee Carolyn S, Budev Marie M, Matthay Michael A, Church Gwynne, Brady Sandra, Uchida Tokujiro, Ishizaka Akitoshi, Lara Abigail, Ranes Justin L, deCamp Malcom M, Arroliga Alejandro C
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California 94143-0130, USA.
J Heart Lung Transplant. 2007 Jul;26(7):675-80. doi: 10.1016/j.healun.2007.04.002.
Primary graft dysfunction, formerly termed reperfusion pulmonary edema, is the leading cause of short-term complications after lung transplantation. New evidence shows that alveolar type I epithelial cells play an active role in alveolar fluid transport and are therefore presumed to be critical in the absorption of pulmonary edema. We tested the potential relevance of a novel marker of alveolar type I cell injury, the receptor for advanced glycation end-products (RAGE), to short-term outcomes of lung transplantation.
The study was a prospective, observational cohort study of 20 patients undergoing single lung, bilateral lung or combined heart-lung transplantation. Plasma biomarkers were measured 4 hours after allograft reperfusion.
Higher plasma RAGE levels were associated with a longer duration of mechanical ventilation and longer intensive care unit length of stay, in contrast to markers of alveolar type II cell injury, endothelial injury and acute inflammation. Specifically, for every doubling in plasma RAGE levels, the duration of mechanical ventilation increased on average by 26 hours, adjusting for ischemia time (95% confidence interval [CI] 7.4 to 44.7 hours, p = 0.01). Likewise, for every doubling of plasma RAGE levels, intensive care unit length of stay increased on average by 1.8 days, again adjusting for ischemia time (95% CI 0.13 to 3.45 days p = 0.04). In contrast, the clinical diagnosis of primary graft dysfunction was not as predictive of these short-term outcomes.
Higher levels of plasma RAGE measured shortly after reperfusion predicted poor short-term outcomes from lung transplantation. Elevated plasma RAGE levels may have both pathogenetic and prognostic value in patients after lung transplantation.
原发性移植肺功能障碍,以前称为再灌注肺水肿,是肺移植后短期并发症的主要原因。新证据表明,I型肺泡上皮细胞在肺泡液体转运中起积极作用,因此被认为在肺水肿吸收中起关键作用。我们测试了一种新型的I型肺泡细胞损伤标志物——晚期糖基化终产物受体(RAGE)与肺移植短期预后的潜在相关性。
本研究是一项对20例接受单肺、双肺或心肺联合移植患者的前瞻性观察队列研究。在移植肺再灌注4小时后测量血浆生物标志物。
与II型肺泡细胞损伤、内皮损伤和急性炎症标志物相比,较高水平的血浆RAGE与机械通气时间延长和重症监护病房住院时间延长有关联。具体而言,血浆RAGE水平每增加一倍,机械通气时间平均增加26小时,校正缺血时间后(95%置信区间[CI]7.4至44.7小时,p = 0.01)。同样,血浆RAGE水平每增加一倍,重症监护病房住院时间平均增加1.8天,再次校正缺血时间后(95%CI 0.13至3.45天,p = 0.04)。相比之下,原发性移植肺功能障碍的临床诊断对这些短期预后的预测性较差。
再灌注后不久测得的较高血浆RAGE水平预示着肺移植短期预后不良。血浆RAGE水平升高可能对肺移植患者具有发病机制和预后价值。