Luckraz Heyman, Goddard Martin, McNeil Keith, Atkinson Carl, Sharples Linda D, Wallwork John
Transplant Unit, Papworth Hospital, Papworth Everard, Cambridge, United Kingdom.
Ann Thorac Surg. 2006 Oct;82(4):1212-8. doi: 10.1016/j.athoracsur.2006.03.070.
Acute rejection, a vascular-based disorder, has been identified as the major risk factor for obliterative bronchiolitis (OB), an airway-based pathology. This study investigated the hypothesis that changes to the microvascular blood supply of small airways were associated with the development of OB, thus providing a possible link between an acute vascular insult (acute rejection) and chronic airway changes (OB).
Microvasculature of 695 small airways (99 patients) was assessed in post-mortem lung allograft specimens using monoclonal antibodies for von Willebrand factor and CD31. Group A consisted of 343 small airways from 58 patients with no evidence of OB. The remaining 41 patients had histological evidence of OB in some of their small airways and grouped as B, C, and D with some patients contributing to all three groups ie, their lung specimen had some small airways which were completely obliterated with OB, some airways which were partially obliterated and some small airways without any histological evidence of OB development. Thus group B consisted of 145 small airways (34 patients) without OB. Group C consisted of 171 small airways with partial luminal obstruction (36 patients). Group D consisted of 36 small airways (14 patients) with complete luminal obliteration.
Airway circumference (mean +/- standard deviation) was 2.36 +/- 0.37, 2.41 +/- 0.51, 2.49 +/- 0.51, and 2.57 +/- 0.79 mm, respectively (p = 0.40). Mean number of blood vessels per unit length of airway circumference was 4.12 +/- 1.1, 1.58 +/- 0.61, 2.42 +/- 1.06, and 4.42 +/- 1.46 vessels/mm, respectively (p < 0.001). Blood vessels with circumference greater than 0.2 mm were present in 100%, 64%, 39%, and 7% of small airways, respectively (p < 0.001). Univariate and multivariate analyses (donor and recipient age, sex, and cytomegalovirus status, recipient pretransplant diagnosis, ischemic times, acute rejection and infective episodes, postoperative survival days, recipient group [A to D], blood vessels per unit length, and airway circumference) confirmed that reduction in blood vessels per unit length was associated with the development of OB and was time-independent.
Obliterative bronchiolitis was preceded by a decrease in microvascular supply to the small airways (group B). The subsequent onset of airway scarring (groups C and D) was associated with an increased number of significantly smaller vessels, suggestive of neovascularization.
急性排斥反应是一种基于血管的疾病，已被确认为闭塞性细支气管炎（OB）的主要危险因素，后者是一种基于气道的病理状态。本研究调查了以下假设：小气道微血管血供的变化与OB的发生有关，从而在急性血管损伤（急性排斥反应）和慢性气道变化（OB）之间提供了一种可能的联系。
使用针对血管性血友病因子和CD31的单克隆抗体，在尸检肺移植标本中评估了695个小气道（99例患者）的微血管系统。A组由58例无OB证据患者的343个小气道组成。其余41例患者的一些小气道有OB的组织学证据，并分为B、C和D组，一些患者分属所有三组，即他们的肺标本中有一些小气道被OB完全闭塞，一些气道部分闭塞，还有一些小气道没有OB发展的任何组织学证据。因此，B组由145个无OB的小气道（34例患者）组成。C组由171个有部分管腔阻塞的小气道（36例患者）组成。D组由36个管腔完全闭塞的小气道（14例患者）组成。
气道周长（平均值±标准差）分别为2.36±0.37、2.41±0.51、2.49±0.51和2.57±0.79mm（p = 0.40）。气道周长单位长度的平均血管数分别为4.12±1.1、1.58±0.61、2.42±1.06和4.42±1.46条/毫米（p < 0.001）。周长大于0.2mm的血管分别存在于100%、64%、39%和7%的小气道中（p < 0.001）。单因素和多因素分析（供体和受体年龄、性别、巨细胞病毒状态、受体移植前诊断、缺血时间、急性排斥反应和感染发作、术后存活天数、受体组[A至D]、单位长度血管数和气道周长）证实，单位长度血管数减少与OB的发生有关，且与时间无关。
在闭塞性细支气管炎发生之前，小气道的微血管供应减少（B组）。随后气道瘢痕形成的发生（C组和D组）与数量增加的明显较小的血管有关，提示新生血管形成。
