Jackson Christopher H, Sharples Linda D, McNeil Keith, Stewart Susan, Wallwork John
MRC Biostatistics Unit, University Forvie Site, Cambridge, UK.
J Heart Lung Transplant. 2002 Jun;21(6):658-66. doi: 10.1016/s1053-2498(02)00381-9.
Bronchiolitis obliterans syndrome (BOS), defined as an irreversible, staged decline in forced expiratory volume in 1 second (FEV(1)), is an established marker of obliterative bronchiolitis. Potential causes of BOS include sub-clinical chronic rejection and/or exaggerated healing response following acute injury. BOS may thus result from two or more distinct processes, both acute and chronic.
A total of 5,916 measurements of FEV(1) from 204 lung transplant recipients surviving at least 6 months after transplantation were analyzed. Follow-up ranged from 6 months to 13 years. By adjusting for the acute effects of rejection, pulmonary infection and measurement variation on FEV(1) trace, patients either had a linear decline characterized by a single acute drop in FEV(1) of >15% at BOS onset, or a chronic linear decline in FEV(1). The fraction having acute onset was estimated. Acute events occurring within the first 6 months were assessed as risk factors for acute onset BOS.
Of the 204 patients, 8% died before BOS onset and 18% were BOS-free at analysis. For 18% of patients, BOS onset followed a chronic linear decline in FEV(1) of 3.7% per year, with a median time of BOS onset >99 months. For 56% of patients, BOS onset followed an acute drop in FEV(1) of median 33.8% (95% CI 19.1% to 39.7%), with median onset time of 52 months. During the first 6 months, acute rejection was significantly and independently associated with acute onset of BOS (relative risk = 1.15 per episode, 95% CI [1.03 to 1.29], p = 0.01), whereas pulmonary infection and cytomegalovirus (CMV) infection were not. Acute BOS onset followed a documented acute event in the previous 6 months in 38 of 114 (33%) of cases.
BOS likely reflects more than one process. Compared with those who had a slow linear decline in lung function, acute BOS onset was associated with acute rejection in the first 6 months, was often triggered by an acute event and had poor prognosis, with obliterative bronchiolitis (OB) the main cause of death.
闭塞性细支气管炎综合征（BOS）被定义为1秒用力呼气容积（FEV₁）的不可逆、分阶段下降，是闭塞性细支气管炎的确切标志。BOS的潜在原因包括亚临床慢性排斥反应和/或急性损伤后的过度愈合反应。因此，BOS可能由两个或更多不同的过程导致，包括急性和慢性过程。
分析了204例肺移植受者在移植后存活至少6个月的5916次FEV₁测量值。随访时间为6个月至13年。通过调整排斥反应、肺部感染和测量变异对FEV₁轨迹的急性影响，患者要么表现为在BOS发作时FEV₁单次急性下降>15%的线性下降，要么表现为FEV₁的慢性线性下降。估计急性发作的比例。将前6个月内发生的急性事件评估为急性发作BOS的危险因素。
在204例患者中，8%在BOS发作前死亡，18%在分析时无BOS。对于18%的患者，BOS发作遵循FEV₁每年3.7%的慢性线性下降，BOS发作的中位时间>99个月。对于56%的患者，BOS发作遵循FEV₁中位数下降33.·8%（95%CI 19.1%至39.7%），中位发作时间为52个月。在最初6个月内，急性排斥反应与BOS的急性发作显著且独立相关（相对风险=每次发作1.15，95%CI[1.03至1.29]，p=0.01），而肺部感染和巨细胞病毒（CMV）感染则不然。在114例（33%）病例中的38例中，急性BOS发作发生在之前6个月记录的急性事件之后。
BOS可能反映了不止一个过程。与肺功能缓慢线性下降的患者相比，急性BOS发作与最初6个月内的急性排斥反应相关，常由急性事件触发，预后较差，闭塞性细支气管炎（OB）是主要死因。
