Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation.
BACKGROUND
Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation.


OBJECTIVE
To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications.


METHODS
Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications.


RESULTS
Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05).


CONCLUSIONS
These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.
1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Bryan D
BD
Kraft
2 Department of Anesthesiology, and.
Hagir B
HB
Suliman
1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Eli C
EC
Colman
1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Kamran
K
Mahmood
3 Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Matthew G
MG
Hartwig
1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.|2 Department of Anesthesiology, and.
Claude A
CA
Piantadosi
1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine.
Scott L
SL
Shofer
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics*; D003251:Constriction, Pathologic / Q000235:genetics; D003550:Cystic Fibrosis / Q000601:surgery; D005260:Female; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000601:surgery; D007902:Length of Stay; D008171:Lung Diseases / Q000601:surgery*; D017563:Lung Diseases, Interstitial / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000235:genetics; D010092:Oximetry; D011183:Postoperative Complications / Q000235:genetics*; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction; D042787:Receptor, TIE-2 / Q000235:genetics; D012131:Respiratory Insufficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000601:surgery; D019737:Transplants / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C501162:FLT1 protein, human; C000588866:KDR protein, human; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
angiogenic proteins; bronchial diseases; cell hypoxia; lung transplantation; oximetry