BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: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.
Authors: X Jiang; T T Nguyen; W Tian; Y K Sung; K Yuan; J Qian; J Rajadas; J-M Sallenave; N P Nickel; V de Jesus Perez; M Rabinovitch; M R Nicolls Journal: Am J Transplant Date: 2015-02-27 Impact factor: 8.086
Authors: Ashok N Babu; Tomohiro Murakawa; Joshua M Thurman; Edmund J Miller; Peter M Henson; Martin R Zamora; Norbert F Voelkel; Mark R Nicolls Journal: J Clin Invest Date: 2007-12 Impact factor: 14.808
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Authors: Bryan D Kraft; Hagir B Suliman; Eli C Colman; Kamran Mahmood; Matthew G Hartwig; Claude A Piantadosi; Scott L Shofer Journal: Am J Respir Crit Care Med Date: 2016-03-01 Impact factor: 21.405
Authors: Xinguo Jiang; Wen Tian; Allen B Tu; Shravani Pasupneti; Eric Shuffle; Petra Dahms; Patrick Zhang; Haoliang Cai; Thanh T Dinh; Bo Liu; Corey Cain; Amato J Giaccia; Eugene C Butcher; M Celeste Simon; Gregg L Semenza; Mark R Nicolls Journal: Circulation Date: 2019-01-22 Impact factor: 29.690
Authors: Rebecca Liu; Jonathan Merola; Thomas D Manes; Lingfeng Qin; Gregory T Tietjen; Francesc López-Giráldez; Verena Broecker; Caodi Fang; Catherine Xie; Ping-Min Chen; Nancy C Kirkiles-Smith; Dan Jane-Wit; Jordan S Pober Journal: JCI Insight Date: 2018-03-08
Authors: Mohammad A Khan; Christian Maasch; Axel Vater; Sven Klussmann; John Morser; Lawrence L Leung; Carl Atkinson; Stephen Tomlinson; Peter S Heeger; Mark R Nicolls Journal: Proc Natl Acad Sci U S A Date: 2013-03-25 Impact factor: 11.205