Plasma Cytokines and Chemokines in Primary Graft Dysfunction Post-Lung Transplantation

Hoffman, Seth A; Wang, L.; Shah, Chirag V.; Ahya, Vivek N.; Pochettino, Alberto; Olthoff, Kim M.; Shaked, Abraham; Wille, Keith; Lama, Vibha N.; Milstone, Aaron P.; Ware, Lorraine B.; Orens, Jonathan B.; Weinacker, Ann; Demissie, Ejigayehu; Bellamy, Scarlett L.; Kawut, Steven M.; Hancock, Wayne W.; Christie, Jason D.

doi:10.1111/j.1600-6143.2008.02497.x

Cited by 101 publications

(84 citation statements)

References 24 publications

(44 reference statements)

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“…LTOG is an NHLBI-funded prospective cohort study of lung transplant recipients with the primary aim of examining clinical and genetic risk factors for PGD at nine United States centers (a full list of investigators and participating centers appears before the REFERENCES section) (22)(23)(24)(25)(26)(27)(28). Based on a reported association between obesity and early mortality after lung transplantation for COPD and ILD (21), we restricted our study sample to 512 adult LTOG participants with COPD or ILD who underwent single or bilateral lung transplantation between March 2002 and July 2009 and who had complete exposure and outcome data.…”

Section: Methods Study Design and Participantsmentioning

confidence: 99%

Obesity and Primary Graft Dysfunction after Lung Transplantation

Lederer¹,

Kawut

Wickersham

et al. 2011

Am J Respir Crit Care Med

132

102

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Rationale: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation. Objectives: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation. Methods: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios. Measurements and Main Results: Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30-50%) for each 5 kg/m 2 increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sexadjusted P ¼ 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass. Conclusions: Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.

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Section: Methods Study Design and Participantsmentioning

confidence: 99%

Obesity and Primary Graft Dysfunction after Lung Transplantation

Lederer¹,

Kawut

Wickersham

et al. 2011

Am J Respir Crit Care Med

132

102

View full text Add to dashboard Cite

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“…Adiposity is associated with inflammatory "adipokines" (including leptin) and other cytokines, such as IL-6 and monocyte chemotactic protein-1 (38,39). These factors have been associated with PGD, a leading cause of early mortality after lung transplantation (40,41). Our study extends the association between leptin and PGD to include mortality, at least among those who did not receive CPB during transplant surgery, consistent with previous work in the same cohort that identified CPB as an effect modifier of the associations of both obesity and leptin with PGD (6).…”

Section: Original Articlementioning

confidence: 99%

Body Composition and Mortality after Adult Lung Transplantation in the United States

Singer¹,

Peterson²,

Snyder³

et al. 2014

Am J Respir Crit Care Med

113

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Rationale: Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed before implementation of the lung allocation score (LAS)-based organ allocation system in the United States Objectives: To determine the associations of body mass index (BMI) and plasma leptin levels with survival after lung transplantation.Methods: We used multivariable-adjusted regression models to examine associations between BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual X-ray absorptiometry in 142 adult lung transplant candidates.Measurements and Main Results: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m 2 ), overweight , and class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI , 18.5) was associated with a 35% increased rate of death (95% confidence interval, 10-66%). Class II-III obesity (BMI > 35 kg/m 2 ) was associated with a nearly twofold increase in mortality (hazard ratio, 1.9; 95% confidence interval, 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (P for interaction = 0.03). A BMI greater than or equal to 30 kg/m 2 was 26% sensitive and 97% specific for total body fat-defined obesity.Conclusions: A BMI of 30.0-34.9 kg/m 2 is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps because of its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI greater than or equal to 30 kg/m 2 may no longer contraindicate lung transplantation.

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“…A variety of clinical risk factors for PGD have been identified with contributions from the donor (3)(4)(5)(6)(7), the recipient (3)(4)(5)(7)(8)(9)(10), and operative variables (4,5,8,11). In addition, a number of biomarkers have been associated with increased risk of PGD, including markers of innate and adaptive immune activation, epithelial and endothelial injury, coagulation, vascular permeability, and lipid peroxidation (2,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Despite identification of these clinical and biomarker predictors of PGD, the mechanisms leading to PGD are not well understood, and there are no specific therapeutic interventions for PGD.…”

Section: Introductionmentioning

confidence: 99%