Sundaresan S, Trulock E P, Mohanakumar T, Cooper J D, Patterson G A
Department of Surgery, Washington University School of Medicine, Barnes Hospital, St. Louis, Missouri 63110, USA.
Ann Thorac Surg. 1995 Nov;60(5):1341-6; discussion 1346-7. doi: 10.1016/0003-4975(95)00751-6.
Bronchiolitis obliterans syndrome (BOS) is the main cause of late morbidity and mortality in lung transplantation. This study was designed to accurately determine the prevalence of this syndrome of chronic lung allograft dysfunction (which is presumed to be due to chronic rejection).
A retrospective analysis was done of 212 consecutive lung transplantations performed at Barnes Hospital between July 1988 and March 1994 to characterize the prevalence and course of BOS. One hundred eighty-seven transplant recipients survived at least 3 months after transplantation, putting them at risk for BOS. Recipients free of BOS (group I) were distinguished from those with BOS (group II) based on the presence of declining spirometry (forced expiratory volume in 1 second persistently less than 80% of previous baseline) or histologic obliterative bronchiolitis in group II.
There were 110 transplantations in group I (59%) and 77 in group II (41%). At follow-up, BOS was detected using the following criteria: declining forced expiratory volume in 1 second alone, 40 of 77 (52%); positive histologic results alone, 7 of 77 (9.1%); and both, 30 of 77 (38.9%). Declining spirometry was the most common initial sign of BOS onset (57 of 77, 74%). There were no differences between groups with respect to age, sex, indication for transplantation, or type of transplantation performed. The mortality rate was significantly higher with BOS (group II, 22 of 77 [28.6%] versus group I, 8 of 110 [7.3%]; p = 0.001) and was not related to either the type of transplantation performed or the indication for transplantation. Follow-up of group II (mean 35.1 months; range, 7.1 to 63.7 months) showed a delay until BOS onset (16.1 +/- 1.2 months); when BOS was fatal, death ensued within 11.5 +/- 2.4 months of its onset. Comparison of the first and last quartiles of recipients in this series (QTR1 versus QTR4, 53 patients in each) demonstrated a higher prevalence of BOS in QTR1 (24 with BOS of 43 at risk [55.8%] versus QTR4, 5 with BOS of 52 at risk [9.6%]; p < 0.001) and a worse BOS functional score in QTR1 (2.2 +/- 0.2 versus QTR4, 0.8 +/- 0.2; p = 0.007).
(1) Bronchiolitis obliterans syndrome is truly a clinical syndrome, not simply a pathologic entity; (2) BOS displays considerable latency in onset and progression; (3) lung transplant recipients must therefore be followed up for a sufficient interval to determine the actual prevalence and mortality rate of BOS; and (4) the prevalence and mortality rates of BOS are higher than previously appreciated, exceeding 50% and 40%, respectively.
闭塞性细支气管炎综合征(BOS)是肺移植术后晚期发病和死亡的主要原因。本研究旨在准确确定这种慢性肺移植功能障碍综合征(推测由慢性排斥反应引起)的患病率。
对1988年7月至1994年3月期间在巴恩斯医院连续进行的212例肺移植进行回顾性分析,以描述BOS的患病率和病程。187例移植受者在移植后至少存活3个月,有发生BOS的风险。根据肺活量测定值下降(第1秒用力呼气量持续低于先前基线的80%)或组织学上的闭塞性细支气管炎,将无BOS的受者(I组)与有BOS的受者(II组)区分开来。
I组有110例移植(59%),II组有77例(41%)。在随访中,使用以下标准检测到BOS:仅第1秒用力呼气量下降,77例中的40例(52%);仅组织学结果阳性,77例中的7例(9.1%);两者均有,77例中的30例(38.9%)。肺活量测定值下降是BOS发病最常见的初始体征(77例中的57例,74%)。两组在年龄、性别、移植指征或移植类型方面无差异。BOS组的死亡率显著更高(II组,77例中的22例[28.6%],而I组,110例中的8例[7.3%];p = 0.001),且与所进行的移植类型或移植指征均无关。II组的随访(平均35.1个月;范围,7.1至63.7个月)显示直到BOS发病有延迟(16.1±1.2个月);当BOS致命时,在其发病后11.5±2.4个月内死亡。对本系列中受者的第一个和最后一个四分位数进行比较(QTR1与QTR4,每组53例患者)显示,QTR1中BOS的患病率更高(43例有风险者中有24例患BOS[55.8%],而QTR4中,52例有风险者中有5例患BOS[9.6%];p < 0.001),且QTR1中BOS功能评分更差(2.2±0.2对QTR4,0.8±0.2;p = 0.007)。
(1)闭塞性细支气管炎综合征确实是一种临床综合征,而非仅仅是一种病理实体;(2)BOS在发病和进展方面有相当长的潜伏期;(3)因此,必须对肺移植受者进行足够长时间的随访,以确定BOS的实际患病率和死亡率;(4)BOS的患病率和死亡率高于先前的认识,分别超过50%和40%。