Luckraz Heyman, Goddard Martin, McNeil Keith, Atkinson Carl, Charman Susan C, Stewart Susan, Wallwork John
Transplant Unit, Papworth Hospital, Cambridge, UK.
J Heart Lung Transplant. 2004 May;23(5):527-31. doi: 10.1016/j.healun.2003.07.003.
There is strong evidence that obliterative bronchiolitis (OB) in lung transplant recipients is related to acute rejection as graded by parenchymal perivascular infiltrates. OB (chronic rejection) is a small airways, rather than a parenchymal, scarring process. Moreover, there has been no study of the microcirculation in the small airways in lung transplantation. This study assesses the microvasculature around small airways (SA) in post-mortem lung allograft specimens.
The microvasculature of SA (n = 19) from 5 patients who died within 24 hours of lung transplantation (Group A) and SA in OB lungs (11 patients, median post-transplant survival 1,371 days) was assessed by the use of monoclonal antibodies to the vascular endothelium, namely von Willebrand factor (vWF) and CD31. The second group was further sub-divided into Group B (airways not obliterated, n = 18), Group C (sub-total airways obliteration, n = 21) and Group D (airways with total luminal obstruction, n = 14).
The measured median circumference of the SA in the 4 groups was 2.1, 2.1, 2.5 and 2.3 mm, respectively (p = 0.66). Using CD31 as the endothelial marker, the median number of blood vessels per unit length of airway circumference (BVPL) was 3.5 vessels/mm for Group A, 0.8 for Group B, 1.3 for Group C and 2.8 for Group D, (p < 0.001). Large blood vessels (circumference >0.20 mm) were present in 95%, 11%, 14% and 21% of each group, respectively (p < 0.001). Similar trends were confirmed with the vWF endothelial antibodies.
OB after lung transplantation is associated with a decrease in microvascular supply to the small airway. This ischemic event may lead to airway damage or increase the tendency to repair by scarring. The small airways then appear to respond to this insult by angiogenesis, which may either occur too late to prevent permanent airway damage or be inadequate in restoring adequate blood supply to the airway.
有强有力的证据表明，肺移植受者的闭塞性细支气管炎（OB）与根据实质血管周围浸润分级的急性排斥反应有关。OB（慢性排斥反应）是一种小气道而非实质的瘢痕形成过程。此外，尚未有关于肺移植中小气道微循环的研究。本研究评估了肺移植术后尸检肺移植标本中小气道（SA）周围的微血管系统。
使用针对血管内皮的单克隆抗体，即血管性血友病因子（vWF）和CD31，评估了5例在肺移植后24小时内死亡患者（A组）的SA（n = 19）以及OB肺中的SA（11例患者，移植后中位生存时间1371天）的微血管系统。第二组进一步分为B组（气道未闭塞，n = 18）、C组（气道部分闭塞，n = 21）和D组（气道完全阻塞，n = 14）。
4组中SA的测量中位周长分别为2.1、2.1、2.5和2.3毫米（p = 0.66）。以CD31作为内皮标志物，气道周长单位长度的血管中位数（BVPL）在A组为3.5条/毫米，B组为0.8条，C组为1.3条，D组为2.8条（p < 0.001）。每组中分别有95%、11%、14%和21%存在大血管（周长>0.20毫米）（p < 0.001）。使用vWF内皮抗体也证实了类似趋势。
肺移植后的OB与小气道微血管供应减少有关。这种缺血事件可能导致气道损伤或增加瘢痕修复的倾向。然后小气道似乎通过血管生成对这种损伤做出反应，这可能发生得太晚而无法防止永久性气道损伤，或者不足以恢复气道的充足血液供应。
