Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.
Pulmonary Department, Meir Medical Center, Kfar Saba, Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Chest. 2012 Apr;141(4):1047-1054. doi: 10.1378/chest.11-0284. Epub 2011 Sep 22.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a 3-year median survival. Lung volume and diffusion capacity at rest are usually used to monitor the clinical course. Because of high mortality, identification of patients at high risk is crucial for treatment strategies such as lung transplantation (LTX). This study was designed to determine if tumor markers could accurately characterize disease severity and survival in patients with IPF.
The study population consisted of 61 patients with progressive IPF referred for LTX. Pulmonary function tests, cardiopulmonary exercise test, 6-min walk distance test, and Doppler echocardiogram were assessed at baseline and compared with tumor marker levels. Participants were prospectively followed for at least 25 months to determine the relationship between test parameters and survival. Tumor marker levels were reassessed in patients who underwent LTX. Forty-one age- and sex-matched patients (21 LTX recipients) with COPD served as control subjects.
In the IPF group, nine patients (14.7%) died during follow-up and 20 (32.8%) underwent LTX. Univariate analysis showed correlations between carbohydrate antigen (CA) 125 and FEV(1) % (P = .0001). CA 19-9 yielded the best correlations with exercise parameters and PAP. Significant correlation with survival was noted with CA 15-3 (P = .04) only. All tumor marker levels decreased significantly following LTX, except CA 125. CA 15-3 had the largest decrease (P = .001). Among the COPD group, tumor marker levels before LTX were significantly lower compared with the IPF and did not decrease following LTX. No patient in either group developed malignancy.
CA 15-3 levels may predict disease severity in IPF. Levels decreased in patients with IPF but not with COPD following LTX and were not associated with malignancy. This preliminary observation suggests that mucin has a role in the pathogenesis of IPF and possibly is a marker for disease activity.
特发性肺纤维化（IPF）是一种进行性疾病，中位生存期为 3 年。静息时的肺容积和弥散能力通常用于监测临床病程。由于死亡率高，识别高危患者对于肺移植（LTX）等治疗策略至关重要。本研究旨在确定肿瘤标志物是否能准确描述 IPF 患者的疾病严重程度和生存情况。
研究人群由 61 名进行性 IPF 患者组成，这些患者因 LTX 而被转诊。在基线时评估了肺功能测试、心肺运动测试、6 分钟步行距离测试和多普勒超声心动图，并与肿瘤标志物水平进行了比较。对参与者进行了至少 25 个月的前瞻性随访，以确定测试参数与生存之间的关系。在接受 LTX 的患者中重新评估了肿瘤标志物水平。41 名年龄和性别匹配的 COPD 患者（21 名 LTX 受者）作为对照组。
在 IPF 组中，9 名患者（14.7%）在随访期间死亡，20 名患者（32.8%）接受了 LTX。单因素分析显示，CA125 与 FEV1%之间存在相关性（P=.0001）。CA19-9 与运动参数和 PAP 的相关性最好。仅 CA15-3 与生存有显著相关性（P=.04）。除 CA125 外，所有肿瘤标志物水平在 LTX 后均显著降低。CA15-3 下降幅度最大（P=.001）。在 COPD 组中，LTX 前的肿瘤标志物水平明显低于 IPF 组，且 LTX 后无下降。两组均无患者发生恶性肿瘤。
CA15-3 水平可能预测 IPF 的疾病严重程度。在接受 LTX 的 IPF 患者中，水平降低，但在接受 LTX 的 COPD 患者中没有降低，且与恶性肿瘤无关。这一初步观察结果表明，黏蛋白在 IPF 的发病机制中起作用，可能是疾病活动的标志物。
