Risk factors for primary graft dysfunction after lung transplantation

Whitson, Bryan A.; Nath, Dilip S.; Johnson, Adelaide M.; Walker, Adam; Prekker, Matthew E.; Radosevich, David M.; Herrington, Cynthia; Dahlberg, Peter S.

doi:10.1016/j.jtcvs.2005.08.039

Cited by 173 publications

(162 citation statements)

References 20 publications

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…In part, this is due to the high incidence (11-25%) of PGD, even in well-preserved ''ideal organs'' (23)(24)(25)(26). The use of the Pa O 2 /FI O 2 index, or P/F ratio, for assessing acute lung dysfunction from acute lung injury (index < 300) and adult respiratory distress syndrome (index < 200) is the accepted standard (27), and the use of the P/F ratio in assessing PGD has recently been established (23,28). In this study, we applied the P/F ratio as a measure of acute lung injury/ PGD and found a significant correlation of PGD with anti-col(V) immune status before transplantation, a novel finding with a number of important implications for lung transplantation.…”

Section: Discussionmentioning

confidence: 99%

Th-17, Monokines, Collagen Type V, and Primary Graft Dysfunction in Lung Transplantation

Bobadilla¹,

Love²,

Jankowska‐Gan³

et al. 2008

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that collagen type V (col [V]), stimulates IL-17-dependent cellular immunity after lung transplantation. Objectives: To determine whether patients with end-stage lung disease develop pretransplant col(V)-specific cellular immunity, and if so, the impact of this response on PGD. Methods: Trans-vivo delayed-type hypersensitivity (TV-DTH) assays were used to evaluate memory T-cell responses to col(V) in 55 patients awaiting lung transplantation. Pa O 2 /FI O 2 index data were used to assess PGD. Univariate risk factor analysis was performed to identify variables associated with PGD. Rats immunized with col(V) or irrelevant antigen underwent lung isografting to determine if prior anti-col(V) immunity triggers PGD in the absence of alloreactivity. Measurements and Main Results: We found that 58.8% (10/17) of patients with idiopathic pulmonary fibrosis, and 15.8% (6/38) of patients without idiopathic pulmonary fibrosis tested while on the wait list for a lung transplant were col(V) DTH positive. Col(V) reactivity was CD4 + T-cell and monocyte mediated, and dependent on IL-17, IL-1b, and tumor necrosis factor (TNF)-a. Pa O 2 /FI O 2 indices were impaired significantly 6-72 hours after transplantation in col(V)-reactive versus nonreactive patients. Univariate risk factor analysis identified only preoperative TV-DTH to col(V) and ischemic time as predictors of PGD. Finally, in a rat lung isograft model, col(V) sensitization resulted in significantly lower Pa O 2 /FI O 2 , increased local TNF-a and IL-1b production, and a moderate-to-severe bronchiolitis/ vasculitis when compared with control isografts. Conclusions: The data suggest that activation of innate immunity by col(V)-specific Th-17 memory cells represents a novel pathway to PGD after lung transplantation.Keywords: lung transplantation; primary graft dysfunction; collagen type V; autoimmunity; memory T cellThe historic paradigm of allograft failure due primarily to humoral and cell-mediated immune responses to foreign major histocompatability complex (MHC) antigens has recently been challenged by additional hypotheses (1-3). Although it is clear that immunity to donor human leukocyte antigen (HLA) serves a significant role in mediating allograft rejection, recent evidence suggests that self-antigens exposed during ischemiareperfusion injury may, under some circumstances, present an equal, if not greater, barrier to graft acceptance (4-6). In lung transplantation, one such cryptic self-antigen is collagen type-V (col[V]) (2). Col(V) is classified as a minor fibrillar collagen and, in the human lung, the ratio of matrix collagens is 86:28:8:1.6 (for collagens I, III, IV, and V, respectively) (7). Under normal physiologic conditions, col(V) coassembles into heterotypic fibrils with the major fibrillar collagen type I (8, 9). In fact, the majority of the col(V) monomer is normally partitioned ...

show abstract

Section: Discussionmentioning

confidence: 99%

Th-17, Monokines, Collagen Type V, and Primary Graft Dysfunction in Lung Transplantation

Bobadilla¹,

Love²,

Jankowska‐Gan³

et al. 2008

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Patients are scored on this grading system at the time immediately posttransplant, and then at 24, 48, and 72 h posttransplant. Those who have PGD 3 persisting to the 72-h point have the worst short-and long-term outcomes (Whitson et al 2006).…”

Section: Postoperative Carementioning

confidence: 99%

Overview of Clinical Lung Transplantation

Yeung

Keshavjee

2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short-and long-term outcomes in the near future.

show abstract

“…Some studies 3 have suggested that only the diagnosis of pulmonary arterial hypertension itself increases the risk of PGD; other studies 29 suggest that each higher increment of pulmonary artery pressure (from any underlying lung disease) translates to an increase in risk of PGD. In addition, because patients with significant pulmonary hypertension require CPB to undergo the transplantation procedure, it is difficult to tease out the respective causal roles.…”

Section: Discussionmentioning

confidence: 99%

Soluble P-Selectin and the Risk of Primary Graft Dysfunction After Lung Transplantation

Kawut

Okun

Shimbo

et al. 2009

Chest

View full text Add to dashboard Cite

show abstract

Risk factors for primary graft dysfunction after lung transplantation

Abstract: Our analysis of donor and recipient risk factors for severe primary graft dysfunction identified patient groups at high risk for poor outcomes after lung transplantation that might benefit from treatments aimed at reducing reperfusion injury.

Cited by 173 publications

References 20 publications

Th-17, Monokines, Collagen Type V, and Primary Graft Dysfunction in Lung Transplantation

Th-17, Monokines, Collagen Type V, and Primary Graft Dysfunction in Lung Transplantation

Overview of Clinical Lung Transplantation

Soluble P-Selectin and the Risk of Primary Graft Dysfunction After Lung Transplantation

Contact Info

Product

Resources

About