Milstone A P, Brumble L M, Loyd J E, Ely E W, Roberts J R, Pierson R N, Dummer J S
Department of Allergy, Pulmonary and Critical Care, Vanderbilt University, Nashville, Tennessee, USA.
J Heart Lung Transplant. 2000 Aug;19(8):744-50. doi: 10.1016/s1053-2498(00)00134-0.
Cytomegalovirus (CMV) infection is a major cause of morbidity following lung transplantation, but active CMV infection has not been described before transplantation. Since 1990, we have screened all lung-transplant recipients for CMV infection with viral urine cultures on the day of transplantation. We retrospectively reviewed the medical records of all 102 lung-allograft recipients transplanted between March 1990 and September 1998. Patients with positive urine cultures for CMV were compared to culture negative patients for age, gender, pretransplant diagnosis, time from diagnosis to transplantation, CMV serostatus, use of pretransplant immunosuppression, T-lymphocyte subsets, and presence of fever. Posttransplant outcomes assessed were duration of intubation and hospitalization, acute rejection, frequency of CMV disease, duration of Nashville rabbit antithymocyte serum or globulin (N-RATS/G) and ganciclovir, and survival. Five (5%) of 102 patients had positive urine cultures for CMV; none had symptoms of CMV infection. All 5 had idiopathic pulmonary fibrosis (IPF) (5/5 vs 27/97; p = 0.002). The age, gender, and CMV serostatus of these patients did not differ from the 97 patients in the culture negative group. Four (80%) of the 5 patients with positive cultures were receiving treatment with azathioprine or cyclophosphamide vs only 18 (19%) of the 97 patients with negative cultures (p = 0.007), and all 5 (100%) were receiving steroids compared to 50 (52%) of 97 patients with negative cultures (p = 0.06). Culture-positive IPF patients, when compared with the 27 culture-negative IPF patients, did not differ in any demographic variable or in the use of immunosuppression, but culture-positive patients were more likely to have a CD4/CD8 T-cell subset ratio <1.0 (p = 0.02). Following transplantation, 3 (60%) of 5 IPF patients with positive CMV cultures developed CMV disease compared to 3 (11%) of 27 IPF patients with negative cultures (p = 0.03). Patients with positive cultures also received more days of parenteral antiviral therapy (mean 44 +/- 11 days vs 16 +/- 10 days; p < 0.001). Utilizing pretransplant screening, we have discovered that 16% of patients with IPF had active CMV infection, which was associated with both alterations in their T-cell subsets and a greater risk for CMV disease after transplantation. This occurrence of occult CMV infection in patients with IPF has not been previously recognized, and has important implications.
巨细胞病毒(CMV)感染是肺移植后发病的主要原因,但移植前尚未有活动性CMV感染的相关描述。自1990年以来,我们在移植当天对所有肺移植受者进行病毒尿培养以筛查CMV感染。我们回顾性分析了1990年3月至1998年9月间接受肺移植的102例受者的病历。将CMV尿培养阳性的患者与培养阴性的患者在年龄、性别、移植前诊断、从诊断到移植的时间、CMV血清学状态、移植前免疫抑制的使用情况、T淋巴细胞亚群以及发热情况等方面进行比较。评估的移植后结果包括插管和住院时间、急性排斥反应、CMV疾病的发生率、使用纳什维尔兔抗胸腺细胞血清或球蛋白(N - RATS/G)和更昔洛韦的时间以及生存率。102例患者中有5例(5%)CMV尿培养阳性;均无CMV感染症状。所有5例均患有特发性肺纤维化(IPF)(5/5 vs 27/97;p = 0.002)。这些患者的年龄、性别和CMV血清学状态与培养阴性组的97例患者无差异。5例培养阳性患者中有4例(80%)正在接受硫唑嘌呤或环磷酰胺治疗,而97例培养阴性患者中仅有18例(19%)接受该治疗(p = 0.007),并且所有5例(100%)均接受类固醇治疗,相比之下97例培养阴性患者中有50例(52%)接受该治疗(p = 0.06)。培养阳性的IPF患者与27例培养阴性的IPF患者相比,在任何人口统计学变量或免疫抑制的使用方面均无差异,但培养阳性患者更有可能出现CD4/CD8 T细胞亚群比值<1.0(p = 0.02)。移植后,5例CMV培养阳性的IPF患者中有3例(60%)发生了CMV疾病,而27例培养阴性的IPF患者中有3例(11%)发生了CMV疾病(p = 0.03)。培养阳性的患者接受肠外抗病毒治疗的天数也更多(平均44±11天 vs 16±10天;p < 0.001)。通过移植前筛查,我们发现16%的IPF患者存在活动性CMV感染,这与他们T细胞亚群的改变以及移植后发生CMV疾病的风险增加有关。IPF患者中这种隐匿性CMV感染的情况此前未被认识到,且具有重要意义。