209 Functional TLR4 Polymorphisms Are Associated with Lower Risk of Primary Graft Dysfunction (PGD) after Lung Transplantation

Diamond, Joshua M.; Feng, Rui; Meyer, Nuala J.; Shah, Rupal J.; Kawut, Steven M.; Lederer, DJ; Lee, J.C.; Ahya, Vivek N.; Cantu, Edward; Weinacker, Ann; Bhorade, Sangeeta; Lama, V.N.; Orens, J.; Sonett, Joshua R.; Wille, Keith; Crespo, Maria; Weill, David; Kohl, Benjamin; Arcasoy, Selim M.; Shah, Ashish S.; Shah, Pali D.; Demissie, Ejigayehu; Reynolds, John M.; Belperio, John A.; Wilkes, D.; Ware, L.B.; Palmer, Scott M.; Christie, Jason D.

doi:10.1016/j.healun.2012.01.208

Cited by 5 publications

(2 citation statements)

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“…Genetic variations among recipients related to the pathogenesis of PGD are a focus of interest for understanding why some recipients develop severe PGD and some do not. For example, certain TLR4 polymorphisms have been associated with a decrease risk of PGD (63). Other genetic analysis studies have confirmed the role of TLR polymorphisms in development of PGD.…”

Section: Recipient Risk Factorsmentioning

confidence: 93%

Primary graft dysfunction: what we know

Clausen¹,

Cantu²

2021

J Thorac Dis

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Many advances in lung transplant have occurred over the last few decades in the understanding of primary graft dysfunction (PGD) though effective prevention and treatment remain elusive. This review will cover prior understanding of PGD, recent findings, and directions for future research. A consensus statement updating the definition of PGD in 2016 highlights the growing complexity of lung transplant perioperative care taking into account the increasing use of high flow oxygen delivery and pulmonary vasodilators in the current era. PGD, particularly more severe grades, is associated with worse short-and long-term outcomes after transplant such as chronic lung allograft dysfunction. Growing experience have helped identify recipient, donor, and intraoperative risk factors for PGD. Understanding the pathophysiology of PGD has advanced with increasing knowledge of the role of innate immune response, humoral cell immunity, and epithelial cell injury. Supportive care post-transplant with technological advances in extracorporeal membranous oxygenation (ECMO) remain the mainstay of treatment for severe PGD. Future directions include the evolving utility of ex vivo lung perfusion (EVLP) both in PGD research and potential pretransplant treatment applications. PGD remains an important outcome in lung transplant and the future holds a lot of potential for improvement in understanding its pathophysiology as well as development of preventative therapies and treatment.

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Section: Recipient Risk Factorsmentioning

confidence: 93%

Primary graft dysfunction: what we know

Clausen¹,

Cantu²

2021

J Thorac Dis

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“…Deficiencies in TLR4, as well as TLR4 mutations that attenuate the immune response, have been associated with a lower risk of PGD in animal models. 67,[113][114][115][116][117] In contrast, genetic polymorphisms in tollinteracting protein (TOLLIP), a regulator of TLR signaling, have been associated with an increased risk for PGD. 66 In the latter phase of IRI, activated neutrophils within the allograft release ROS and inflammatory chemokines that promote neutrophil recruitment and cellular death.…”

Section: Innate Immunitymentioning

confidence: 99%

Primary Graft Dysfunction

Natalini

Diamond

2021

Semin Respir Crit Care Med

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Primary graft dysfunction (PGD) is a form of acute lung injury after transplantation characterized by hypoxemia and the development of alveolar infiltrates on chest radiograph that occurs within 72 hours of reperfusion. PGD is among the most common early complications following lung transplantation and significantly contributes to increased short-term morbidity and mortality. In addition, severe PGD has been associated with higher 90-day and 1-year mortality rates compared with absent or less severe PGD and is a significant risk factor for the subsequent development of chronic lung allograft dysfunction. The International Society for Heart and Lung Transplantation released updated consensus guidelines in 2017, defining grade 3 PGD, the most severe form, by the presence of alveolar infiltrates and a ratio of PaO2:FiO2 less than 200. Multiple donor-related, recipient-related, and perioperative risk factors for PGD have been identified, many of which are potentially modifiable. Consistently identified risk factors include donor tobacco and alcohol use; increased recipient body mass index; recipient history of pulmonary hypertension, sarcoidosis, or pulmonary fibrosis; single lung transplantation; and use of cardiopulmonary bypass, among others. Several cellular pathways have been implicated in the pathogenesis of PGD, thus presenting several possible therapeutic targets for preventing and treating PGD. Notably, use of ex vivo lung perfusion (EVLP) has become more widespread and offers a potential platform to safely investigate novel PGD treatments while expanding the lung donor pool. Even in the presence of significantly prolonged ischemic times, EVLP has not been associated with an increased risk for PGD.

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Primary Graft Dysfunction After Lung Transplantation

Porteous

Lee

2017

Clinics in Chest Medicine

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209 Functional TLR4 Polymorphisms Are Associated with Lower Risk of Primary Graft Dysfunction (PGD) after Lung Transplantation

Cited by 5 publications

References 0 publications

Primary graft dysfunction: what we know

Primary graft dysfunction: what we know

Primary Graft Dysfunction

Primary Graft Dysfunction After Lung Transplantation

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