Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation

King, Robert C.; Binns, Oliver A.R.; Rodriguez, Filiberto; Kanithanon, R.Chai; Daniel, Thomas M.; Spotnitz, William D.; Tribble, Curtis G.; Krön, Irving L.

doi:10.1016/s0003-4975(00)01425-9

Cited by 296 publications

(239 citation statements)

References 10 publications

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“…These findings are consistent with reported mortality rates and relative risks in single-center studies for the most severe forms of PGD, including our own (1,2,5). In addition, a recent ISHLT registry report describes PGD as accounting for greater than 30% of mortality in the first 30 days, according to listed cause of death (14,19).…”

Section: Discussionsupporting

confidence: 89%

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The Effect of Primary Graft Dysfunction on Survival after Lung Transplantation

Christie

Kotloff²,

Ahya³

et al. 2005

Am J Respir Crit Care Med

302

212

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Rationale: Primary graft dysfunction is a severe acute lung injury syndrome after lung transplantation. Long-term outcomes of subjects with primary graft dysfunction have not been studied. Objectives: We sought to test the relationship of primary graft dysfunction with both short-and long-term mortality using a large registry. Methods: We used data collected on 5,262 patients in the United Network for Organ Sharing/International Society of Heart and Lung Transplantation registry between 1994 and 2000. We assessed outcomes in all subjects; to assess potential bias from the effects of early mortality, we also evaluated subjects who survived at least 1 year, using Cox proportional hazards models with time-varying covariates. Main Results: The overall incidence of primary graft dysfunction was 10.2% (95% confidence intervals [CI], 9.2, 10.9). The incidence did not vary by year over the period of observation (p ϭ 0.22). All-cause mortality at 30 days was 42.1% for primary graft dysfunction versus 6.1% in patients without graft dysfunction (relative risk ϭ 6.95; 95% CI, 5.98, 8.08; p Ͻ 0.001); among subjects who died by 30 days, 43.6% had primary graft dysfunction. Among patients surviving at least 1 year, those who had primary graft dysfunction had significantly worse survival over ensuing years (hazard ratio, 1.35; 95% CI, 1.07, 1.70; p ϭ 0.011). Adjustment for clinical variables including bronchiolitis obliterans syndrome did not change this relationship. Conclusion: Primary graft dysfunction contributes to nearly half of the short-term mortality after lung transplantation. Survivors of primary graft dysfunction have increased risk of death extending beyond the first post-transplant year.Keywords: acute lung injury; lung transplantation; outcomes; primary graft dysfunction; reperfusion injury Primary graft dysfunction (PGD), also known as primary graft failure, is a form of lung allograft ischemia-reperfusion injury (1, 2). Occurring in the first hours to days after transplantation, the clinical course and pathophysiology of the most severe forms are most similar to the acute respiratory distress syndrome (1,3,4). With an incidence reported between 10 and 25%, and a high mortality (5), PGD represents the leading cause of early death after transplantation (1, 2, 5-8).However, the long-term outcomes of PGD have not been (Received in original form September 20, 2004; accepted in final form March 3, 2005) Supported by grants NHLBI K23 HL04243 and the Craig and Elaine Dobbin Pulmonary Research Fund.Correspondence and requests for reprints should be addressed to

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Section: Discussionsupporting

confidence: 89%

“…systematically studied because of the low numbers of survivors at single centers (2,3,5). In one study, it was suggested that severe ischemia-reperfusion injury increases the risk of chronic rejection and long-term mortality (9); however, others have found no such relationship (3).…”

mentioning

confidence: 99%

The Effect of Primary Graft Dysfunction on Survival after Lung Transplantation

Christie

Kotloff²,

Ahya³

et al. 2005

Am J Respir Crit Care Med

302

212

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“…Early graft injury also contributes to the risk for subsequent episodes of rejection and perhaps even lymphocytic bronchitis and bronchiolitis obliterans (32). A better understanding of lung IRI would facilitate the use of lungs from NHBDs to alleviate the donor shortage.…”

Section: Early Graft Dysfunctionmentioning

confidence: 99%

Lung Transplantation: Opportunities for Research and Clinical Advancement

Wilkes¹

2006

Am J Respir Crit Care Med

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Lung transplantation is the only definitive therapy for many forms of end-stage lung diseases. However, the success of lung transplantation is limited by many factors: (1 ) Too few lungs available for transplantation due to limited donors or injury to the donor lung; (2 ) current methods of preservation of excised lungs do not allow extended periods of time between procurement and implantation; (3 ) acute graft failure is more common with lungs than other solid organs, thus contributing to poorer short-term survival after lung transplant compared with that for recipients of other organs; (4 ) lung transplant recipients are particularly vulnerable to pulmonary infections; and (5 ) chronic allograft dysfunction, manifest by bronchiolitis obliterans syndrome, is frequent and limits long-term survival. Scientific advances may provide significant improvements in the outcome of lung transplantation. The National Heart, Lung, and Blood Institute convened a working group of investigators on June 14-15, 2004, in Bethesda, Maryland, to identify opportunities for scientific advancement in lung transplantation, including basic and clinical research. This workshop provides a framework to identify critical issues related to clinical lung transplantation, and to delineate important areas for productive scientific investigation. Keywords: allograft dysfunction; infection; ischemia-reperfusion injury; lung transplantation; obliterative bronchiolitis; rejectionThe transplantation of organs offers the promise of life-saving and life-enhancing therapy for a variety of ailments. Lung transplantation (LTx) has become an acceptable therapy to palliate patients with a variety of end-stage lung diseases. However, lung transplantation has not turned out to be a panacea for chronic lung disease because of significant limitations in the entire transplant process (Figure 1). First, there are not nearly enough suitable donor lungs to meet the needs of all patients with end-stage lung disease. As a result, more patients die waiting for transplants than from mortality associated with a lung transplant. Second, early graft survival after LTx is worse than for other types of organs transplanted (1). Finally, late survival after successful LTx is hampered by the development of chronic allograft dysfunction and by the life-limiting complications associated with conventional immunosuppressive medications. Two factors impede progress to address these problems: (1 ) lung transplant centers lack the infrastructure to facilitate prospective, multicenter clinical studies of sufficient power to address clinical questions and (2 ) there are too few investigators studying the biology of lung transplantation.The NHLBI convened a workshop on June 14-15, 2004, to better understand these complex problems and to identify strategies to address these and prioritize them. The topics addressed by participants were wide-ranging. They included the following: lung use rates from conventional brain-dead organ donors; safe limits for donor lung function; consideration o...

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“…3,4 Ischemiareperfusion injury is one of the most important causes of early allograft injury and may lead to primary graft dysfunction that in turn contributes to the development of OB. 5,6 Therefore, interventions targeting early immune activation could well result in reduced long-term complications.…”

Section: Introductionmentioning

confidence: 99%