Shah R J, Wickersham N, Lederer D J, Palmer S M, Cantu E, Diamond J M, Kawut S M, Lama V N, Bhorade S, Crespo M, Demissie E, Sonett J, Wille K, Orens J, Weinacker A, Shah P, Arcasoy S, Wilkes D S, Christie J D, Ware L B
Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Am J Transplant. 2014 Feb;14(2):446-52. doi: 10.1111/ajt.12541. Epub 2014 Jan 8.
Inherent recipient factors, including pretransplant diagnosis, obesity and elevated pulmonary pressures, are established primary graft dysfunction (PGD) risks. We evaluated the relationship between preoperative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the Lung Transplant Outcomes Group enrolled between 2002 and 2010. Our primary outcome was Grade 3 PGD on Day 2 or 3. We measured preoperative plasma levels of five biomarkers (CC-16, sRAGE, ICAM-1, IL-8 and Protein C) that were previously associated with PGD when measured at the postoperative time point. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC-16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p<0.001). CC-16 was associated with PGD in nonidiopathic pulmonary fibrosis (non-IPF) subjects (OR for highest quartile of CC-16: 2.87, 95% CI: 1.37, 6.00, p=0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p=0.59). After adjustment, preoperative CC-16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p=0.013) in non-IPF subjects. Our study suggests the importance of preexisting airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pretransplant risk stratification in specific recipients.
包括移植前诊断、肥胖和肺压力升高在内的受者内在因素是已确定的原发性移植物功能障碍(PGD)风险因素。我们评估了术前肺损伤生物标志物与PGD之间的关系,以进一步深入了解受者的发病机制。我们对2002年至2010年期间入组肺移植结果研究组的受者进行了一项前瞻性队列研究。我们的主要结局是术后第2天或第3天出现3级PGD。我们测量了术前血浆中五种生物标志物(CC-16、可溶性晚期糖基化终末产物受体[sRAGE]、细胞间黏附分子-1[ICAM-1]、白细胞介素-8[IL-8]和蛋白C)的水平,这些生物标志物在术后时间点测量时曾与PGD相关。我们使用多变量逻辑回归来调整潜在的混杂因素。在714名受试者中,130名(18%)发生了PGD。PGD受试者的CC-16水平中位数升高(10.1对6.0,p<;0.001)。CC-16与非特发性肺纤维化(非IPF)受试者的PGD相关(CC-16最高四分位数的比值比:2.87,95%置信区间:1.37,6.00,p=0.005),但与IPF受试者无关(比值比1.38,95%置信区间:0.43,4.45,p=0.59)。调整后,术前CC-16水平在非IPF受试者中仍与PGD相关(比值比:3.03,95%置信区间:1.26,7.30,p=0.013)。我们的研究表明既往存在的气道上皮损伤在PGD中的重要性。气道上皮损伤标志物可能有助于特定受者的移植前风险分层。