A classification system for severity of lung dysfunction after lung transplantation: a predictor of outcome

2001 ◽  
Vol 20 (2) ◽  
pp. 223 ◽  
Author(s):  
Y. Sekine ◽  
T. Waddell ◽  
A. Matte-Martyn ◽  
A. Pierre ◽  
M. Deperrot ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Classification System ◽  
Lung Dysfunction

scholarly journals The HMGB1-RAGE axis mediates traumatic brain injury–induced pulmonary dysfunction in lung transplantation

2014 ◽  
Vol 6 (252) ◽  
pp. 252ra124-252ra124 ◽  
Author(s):  
Daniel J. Weber ◽  
Adam S. A. Gracon ◽  
Matthew S. Ripsch ◽  
Amanda J. Fisher ◽  
Bo M. Cheon ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Lung Transplantation ◽  
Inflammatory Responses ◽  
Pulmonary Dysfunction ◽  
Wild Type ◽  
Hmgb1 Protein ◽  
Lung Dysfunction

Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE−/−) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs’ ability to expand), all of which were attenuated in RAGE−/−mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE−/−TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation.

scholarly journals Featured Article: Electroporation-mediated gene delivery of surfactant protein B (SP-B) restores expression and improves survival in mouse model of SP-B deficiency

2017 ◽  
Vol 242 (13) ◽  
pp. 1345-1354 ◽  
Author(s):  
Rebecca C Barnett ◽  
Xin Lin ◽  
Michael Barravecchia ◽  
Rosemary A Norman ◽  
Karen L de Mesy Bentley ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Mouse Model ◽  
Lung Transplantation ◽  
Surfactant Protein ◽  
Cmv Promoter ◽  
Surfactant Protein B ◽  
Lung Dysfunction ◽  
Lung Histology ◽  
Surfactant Protein B Deficiency ◽  
Protein B

Surfactant Protein B Deficiency is a rare but lethal monogenetic, congenital lung disease of the neonate that is unresponsive to any treatment except lung transplantation. Based on the potential that gene therapy offers to treat such intractable diseases, our objective was to test whether an electroporation-based gene delivery approach could restore surfactant protein B expression and improve survival in a compound knockout mouse model of surfactant protein B deficiency. Surfactant protein B expression can be shut off in these mice upon withdrawl of doxycycline, resulting in decreased levels of surfactant protein B within four days and death due to lung dysfunction within four to seven days. Control or one of several different human surfactant protein B-expressing plasmids was delivered to the lung by aspiration and electroporation at the time of doxycycline removal or four days later. Plasmids expressing human surfactant protein B from either the UbC or CMV promoter expressed surfactant protein B in these transgenic mice at times when endogenous surfactant protein B expression was silenced. Mean survival was increased 2- to 5-fold following treatment with the UbC or CMV promoter-driven plasmids, respectively. Histology of all surfactant protein B treated groups exhibited fewer neutrophils and less alveolar wall thickening compared to the control groups, and electron microscopy revealed that gene transfer of surfactant protein B resulted in lamellar bodies that were similar in the presence of electron-dense, concentric material to those in surfactant protein B-expressing mice. Taken together, our results show that electroporation-mediated gene delivery of surfactant protein B-expressing plasmids improves survival, lung function, and lung histology in a mouse model of surfactant protein B deficiency and suggest that this may be a useful approach for the treatment of this otherwise deadly disease. Impact statement Surfactant protein B (SP-B) deficiency is a rare but lethal genetic disease of neonates that results in severe respiratory distress with no available treatments other than lung transplantation. The present study describes a novel treatment for this disease by transferring the SP-B gene to the lungs using electric fields in a mouse model. The procedure is safe and results in enough expression of exogenous SP-B to improve lung histology, lamellar body structure, and survival. If extended to humans, this approach could be used to bridge the time between diagnosis and lung transplantation and could greatly increase the likelihood of affected neonates surviving to transplantation and beyond.

scholarly journals Pannexin-1 channels on endothelial cells mediate vascular inflammation during lung ischemia-reperfusion injury

2018 ◽  
Vol 315 (2) ◽  
pp. L301-L312 ◽  
Author(s):  
Ashish K. Sharma ◽  
Eric J. Charles ◽  
Yunge Zhao ◽  
Adishesh K. Narahari ◽  
Pranav K. Baderdinni ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lung Transplantation ◽  
Vascular Permeability ◽  
Ischemia Reperfusion ◽  
Vascular Inflammation ◽  
Atp Release ◽  
Neutrophil Infiltration ◽  
Wild Type ◽  
Pannexin 1 ◽  
Lung Dysfunction

Ischemia-reperfusion (I/R) injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin-1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after I/R and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was used whereby left lungs underwent 1 h of ischemia and 2 h of reperfusion. Treatment of wild-type mice with Panx1 inhibitors (carbenoxolone or probenecid) significantly attenuated I/R-induced pulmonary dysfunction, edema, cytokine production, and neutrophil infiltration versus vehicle-treated mice. In addition, VE-Cad-CreERT2+/Panx1fl/fl mice (tamoxifen-inducible deletion of Panx1 in vascular endothelium) treated with tamoxifen were significantly protected from IRI (reduced dysfunction, endothelial permeability, edema, proinflammatory cytokines, and neutrophil infiltration) versus vehicle-treated mice. Furthermore, extracellular ATP levels in bronchoalveolar lavage fluid is Panx1-mediated after I/R as it was markedly attenuated by Panx1 antagonism in wild-type mice and by endothelial-specific Panx1 deficiency. Panx1 gene expression in lungs after I/R was also significantly elevated compared with sham. In vitro experiments demonstrated that TNF-α and/or hypoxia-reoxygenation induced ATP release from lung microvascular endothelial cells, which was attenuated by Panx1 inhibitors. This study is the first, to our knowledge, to demonstrate that endothelial Panx1 plays a key role in mediating vascular permeability, inflammation, edema, leukocyte infiltration, and lung dysfunction after I/R. Pharmacological antagonism of Panx1 activity may be a novel therapeutic strategy to prevent IRI and primary graft dysfunction after lung transplantation.

scholarly journals Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation

1992 ◽  
Vol 103 (5) ◽  
pp. 1015-1018 ◽  
Author(s):  
John D. Puskas ◽  
Timothy L. Winton ◽  
John D. Miller ◽  
Masina Scavuzzo ◽  
G. Alexander Patterson
Keyword(s):  
Lung Transplantation ◽  
Single Lung Transplantation ◽  
Lung Dysfunction ◽  
Donor Lung

International Research and Variation in Views of Ethnicity

2012 ◽  
Vol 2 (2) ◽  
pp. 66-72
Author(s):  
Ella Inglebret ◽  
Amy Skinder-Meredith ◽  
Shana Bailey ◽  
Carla Jones ◽  
Ashley France
Keyword(s):  
United States ◽  
Classification System ◽  
International Research ◽  
The United States ◽  
Research Articles ◽  
Journal Articles ◽  
Research Participants ◽  
The Past ◽  
International Scale ◽  
Publication Patterns

The authors in this article first identify the extent to which research articles published in three American Speech-Language-Hearing Association (ASHA) journals included participants, age birth to 18 years, from international backgrounds (i.e., residence outside of the United States), and go on to describe associated publication patterns over the past 12 years. These patterns then provide a context for examining variation in the conceptualization of ethnicity on an international scale. Further, the authors examine terminology and categories used by 11 countries where research participants resided. Each country uses a unique classification system. Thus, it can be expected that descriptions of the ethnic characteristics of international participants involved in research published in ASHA journal articles will widely vary.

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